RARE DISEASE
Spina bifida and other spinal dysraphisms
Spina bifida and other spinal dysraphisms
Spina bifida and other spinal dysraphisms
Synonyms: Isolated spina bifida, Isolated spinal dysraphism
Synonyms: Isolated spina bifida, Isolated spinal dysraphism
Synonyms: Isolated spina bifida, Isolated spinal dysraphism
Drug discovery
3
drugs
With orphan designations
Overview
Overview of Spina Bifida and Spinal Dysraphisms
Spina bifida, a neural tube defect, results from incomplete spinal column closure during embryogenesis, leading to neurological deficits. Spinal dysraphisms encompass a spectrum of disorders, including spina bifida occulta (asymptomatic vertebral defect), meningocele (meningeal sac protrusion), and myelomeningocele (spinal cord exposure). Severity ranges from mild to profound motor/sensory impairments, bladder/bowel dysfunction, and hydrocephalus. Prevention via folic acid supplementation is critical, while multidisciplinary care manages lifelong complications [1][4][6][9].
Burden
Economic: Lifetime care costs average $791,900 per individual; U.S. hospitalizations cost >$1.6 billion annually [1][3].
Clinical: Adults face frequent hospitalizations (34% preventable), with septicemia and skin ulcers as leading causes [3][8].
Psychosocial: Lower health-related quality of life vs. peers, though social well-being may improve over time [13][15].
Therapies
Neonatal surgery for myelomeningocele closure and VP shunting for hydrocephalus [6][15].
Lifelong multidisciplinary care: urology (clean intermittent catheterization), orthopedics (mobility aids), and neurosurgery (tethered cord release) [3][9][15].
Prenatal interventions: Fetal surgery for select myelomeningocele cases to reduce neurological deficits [6][9].
Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare neurological diseases
Research Papers
1,303 drug discovery papers about Spina bifida and other spinal dysraphisms, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,303 drug discovery papers about Spina bifida and other spinal dysraphisms, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-07-01 | Bioinformatics-based prediction and in vitro validation of quercetin’s potential targets in congenital spinal deformity: An exploratory study on its role in osteogenic differentiation
Background Congenital spinal deformities (CSDs) are a class of complex spinal malformations arising from abnormal vertebral development, often associated with aberrant osteogenic differentiation. Quercetin (QUE), a natural flavonoid compound, possesses potent osteogenic properties; however, its specific therapeutic targets and molecular mechanisms in CSDs remain unclear. Objective This study aimed to identify the potential targets of QUE in CSDs treatment and elucidate its regulatory role in osteogenic differentiation. Methods Differentially expressed genes (DEGs) between placental tissues from fetuses with isolated spina bifida and normal controls were identified using the GSE252552 dataset. QUE-associated targets were retrieved from the SwissTargetPrediction database. Intersecting targets were analyzed via protein-protein interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Key modules and genes were systematically screened using weighted gene co-expression network analysis (WGCNA). Machine learning algorithms were employed to identify hub genes. Molecular docking was performed to verify binding affinity. In vitro experiments using human mesenchymal stem cells (hMSCs) were conducted to validate the regulatory effects of QUE on the identified target and osteogenic differentiation. Results A total of 5835 DEGs were identified, and 31 intersecting targets with QUE were obtained. Functional enrichment analyses indicated that these targets were primarily involved in the PI3K-Akt and FoxO signaling pathways. WGCNA identified 1485 module genes significantly correlated with CSDs, yielding 10 intersecting hub genes. Through machine learning screening, Aurora kinase B (AURKB) was identified as the pivotal target. Bioinformatics analysis revealed that AURKB was upregulated in CSD tissues and progressively increased during the osteogenic differentiation of hMSCs. Molecular docking confirmed a strong binding affinity between QUE and AURKB. In vitro experiments demonstrated that QUE treatment promoted hMSC viability and upregulated AURKB protein expression in a dose-dependent manner. Mechanistically, QUE enhanced alkaline phosphatase (ALP) activity, increased mineralized nodule formation, and upregulated osteogenic markers (BMP2 and RUNX2). However, these osteogenic-promoting effects were significantly attenuated by AURKB knockdown. Conclusion This study identified AURKB as a critical target of QUE in CSDs. QUE promoted osteogenic differentiation in hMSCs by upregulating AURKB expression.
2026-04-27 | Anesthetic Management of a Parturient With Lipomyelomeningocele and Tethered Cord for Cesarean Section.
Lipomyelomeningocele (LMMC) presents significant anesthetic challenges due to spinal cord tethering and distorted anatomy, which make the gold-standard neuraxial anesthesia technically difficult and neurologically risky. We report the case of a 29-year-old primigravida with LMMC and prior neurosurgeries scheduled for an elective cesarean section. Given the risk of direct neural injury and unpredictable block spread, a planned general anesthesia (GA) was performed, and a multimodal analgesic strategy was employed. The procedure was uneventful, resulting in a healthy neonate and a mother with excellent pain control and no deviation from her neurological baseline. This case demonstrates that while neuraxial techniques are usually preferred, GA is a safe and necessary alternative for patients with complex spinal dysraphism. Success requires a thorough preoperative neurological assessment, neuroimaging review, and tailored multidisciplinary approach.
2026-04-14 | Advancements in the Treatment and Management of Voiding Dysfunction in Individuals with Spina Bifida.
PURPOSE OF REVIEW: This manuscript aims to provide an overview of the pathophysiology of voiding dysfunction, management goals, and treatment options for individuals with spina bifida in order to better assist providers caring for these patients and their families. RECENT FINDINGS: Recent studies have demonstrated efficacy and safety of beta-3 agonists and onabotulinum toxin A as noninvasive options for management of neurogenic lower urinary tract dysfunction. Studies focusing on patient reported outcomes and health-related quality of life have raised greater awareness of patient goals and socio-environmental factors in the counseling of different treatment options. This review highlights the latest research on the management of voiding dysfunction in patients living with spina bifida. Better understanding of pathophysiology and new developments in non-invasive treatment options have substantially improved long-term durability and outlook for these patients. Future research should aim to identify patient and family goals to better manage expectations and quality of life for this lifelong condition.
2026-02-05 | Cerebrospinal fluid matrix-remodeling biomarkers in neonates with myelomeningocele: MMP-9, TIMP-1, and TGF-β1 expression.
Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases, regulate extracellular matrix remodeling and neural tissue homeostasis. Transforming growth factor β1 modulates inflammation, ECM deposition, and tissue repair. Dysregulation of these pathways may contribute to congenital spinal dysraphism. This study quantified cerebrospinal fluid MMP-9, TIMP-1, and TGF-β1 in neonates with myelomeningocele and evaluated their potential as pathogenic mediators or biomarkers. Preoperative CSF samples were collected from 48 neonates with isolated myelomeningocele (Group 1) and 24 age-matched controls with sterile CSF (Group 2). MMP-9, TIMP-1, and TGF-β1 concentrations were measured via ELISA. Intergroup differences were analyzed, and Pearson correlation assessed relationships among biomarkers. CSF MMP-9 levels were significantly elevated in neonates with myelomeningocele compared to controls (57.12 ± 64.19 ng/mL vs. 11.29 ± 6.79 ng/mL; p < 0.05). TIMP-1 (368.78 ± 220.08 ng/mL vs. 450.04 ± 390.22 ng/mL) and TGF-β1 (2.32 ± 1.44 ng/mL vs. 2.524 ± 1.07 ng/mL) did not differ significantly. MMP-9 correlated positively with TIMP-1 across all subjects (p < 0.05) and with TGF-β1 within the myelomeningocele group (p < 0.05), indicating coordinated regulation of ECM degradation and fibrogenic signaling. Elevated CSF MMP-9 in neonates with myelomeningocele suggests dysregulated ECM remodeling may be associated with neural tube malformation. MMP-9 may serve as a biomarker of ECM dysregulation, providing insights into the pathogenesis of congenital spinal dysraphism and identifying possible targets for future therapeutic interventions.
2025-11-13 | Blood Pressure Optimization During Fetoscopic Repair of Open Spinal Dysraphism: Insights from Advanced Hemodynamic Monitoring
Background/Objectives: Fetoscopic repair of open spinal dysraphism (OSD) is a rare intrauterine procedure performed in specialized fetal surgery centers. Conducted under restrictive fluid management and continuous tocolysis, it poses substantial challenges to maternal hemodynamic stability. Blood pressure optimization with vasopressor boluses is often required, yet intraoperative hemodynamic data remain limited. Methods: This prospective observational study was conducted between December 2023 and January 2025 during fetoscopic repair of OSD at Marburg University Hospital, Germany. Maternal hemodynamics were continuously monitored using pulse contour analysis with the Acumen IQ sensor and HemoSphere platform (Edwards Lifesciences, Irvine, CA, USA). To stabilize arterial pressure, cafedrine/theodrenaline (Akrinor, Ratiopharm, Ulm, Germany) was administered as intravenous boluses. Hemodynamic parameters were analyzed immediately before and after each bolus. Fetal heart rate was assessed as a secondary parameter at predefined intraoperative time points when available. Results: A total of 13 patients and 110 vasopressor boluses were analyzed. Reported values reflect median percent changes; parentheses indicate the total range. Following maternal blood pressure optimization, mean arterial pressure increased by 13.7% (5.9–21.6), systemic vascular resistance index by 23.1% (8.3–36.7), and dP/dtmax by 21.7% (6.3–29.9): p < 0.001 for all. Cardiac index and stroke volume index decreased by −6.7% (−11.8 to −0.6), p < 0.001, and −4.3% (−9.8 to 1.8), p = 0.048, respectively. Fetal heart rate remained stable (+0.4% (−0.8 to 1.5); p = 0.470). A total of 38 HPI alerts were followed by hypotension, with a median latency of 120 s (80–235); 73 alerts were not followed by hypotension during the observation period. Conclusions: Intermittent cafedrine/theodrenaline boluses significantly increased arterial pressure, dP/dtmax, and systemic vascular resistance under conditions of fluid restriction and tocolysis-induced vasodilation. Maternal heart rate remained stable, and cardiac output showed only minor reductions. Fetal heart rate was unchanged following maternal blood pressure treatment, indicating no adverse fetal response to C/T within the observed intraoperative period.
proteins
2026-06-30 | Healthcare utilization in patients with spina bifida and bone fractures.
To compare bone fractures and fracture-related healthcare costs in individuals with and without spina bifida (SB). This is a retrospective observational trial. California's Healthcare Access and Information database was utilized to identify all individuals with SB who sought care in California emergency departments, inpatient hospitals, or ambulatory surgery centres between 2005 and 2017. Bone fracture encounters and associated healthcare utilization factors were compared among individuals with spina bifida vs individuals without spina bifida, matched 5:1 by birth year. Between 2005 and 2017, 20,290 individuals with spina bifida sought care in California emergency departments, inpatient hospitals, or ambulatory surgery centres. Compared with 101,450 individuals in the comparison group, those with spina bifida were more likely to seek care for a bone fracture (OR 1.64, p < 0.001) and more likely to sustain repeat fractures (36% vs 26%, p < 0.001). Individuals with spina bifida sustained more bone fractures per capita at each body location studied, with more than double the fractures per capita at the chest (2.0x), foot (2.1x), pelvis (2.4x), leg (2.5x), and vertebrae (2.5x). Individuals with spina bifida spent more cumulative days hospitalized for bone fractures (mean 9.4 vs 7.6, p < 0.001). Individuals with spina bifida were diagnosed with more bone fractures per capita than age-matched persons without spina bifida.
2025-11-17 | Neuroprotective properties of erythropoietin (Epo) and its receptor (EpoR) in open spinal dysraphism (OSD): an investigation of EpoR expression in a rat OSD model, along with in vitro studies on the neuroprotective effects of Epo on rat spinal cord-derived neural progenitor cells.
Research into treatment options that complement surgery for open spinal dysraphism (OSD) is necessary to further improve outcomes following prenatal or postnatal surgery. We investigated erythropoietin (Epo) and its receptor (EpoR) as a potential neuroprotective agent and target in OSD. Epo- and EpoR-expression was examined on mRNA and immunohistochemical level in neuroplacodes obtained from a rat retinoic acid-induced OSD model at E16, E18, E22. Neural progenitor cells (NPCs) derived from spinal cords of adult Long Evans rats were exposed to varying concentrations of human artificial amniotic fluid (aAF). Cytotoxicity assays were conducted to assess the impact of aAF exposure, with and without Epo. The influence of Epo on NPC's cellular marker expression was analyzed using qRT-PCR. EpoR mRNA expression was elevated significantly on E18 and E22 in OSD- compared to control tissue. EpoR immunoreactivity exhibited consistent expression in ventral and dorsal horns, central canal, and ganglia. It co-stained with Hif-2α, β-III-tubulin, NeuN, and Musashi1. Exposure of NPCs to aAF reduced proliferation and increased death rates dose-dependently. Adding Epo significantly counteracted antiproliferative and cytotoxic aAF effects on NPCs, resulting in similar or lower death rates than those observed in untreated controls. Exposure of NPCs to aAF reduced their expression of neuronal markers. Adding Epo restored their differentiation capacities. Induction of EpoR in neuroplacodes, its co-staining with neuronal and NPC markers, and the neuroprotective effects of Epo on aAF-treated NPCs in vitro establish Epo as a promising candidate for neuroprotective therapies that can supplement surgical measures for OSD.
2024-12-04 | Advanced Tissue-Engineering Approaches for Prenatal Neurosurgical Management of Spinal Dysraphism
Spinal dysraphism arises from neural tube closure defects occurring between 2 and 6 weeks of gestation, leading to severe complications after birth. It is typically classified as either open or closed, depending on whether the defect is covered by skin. Despite advances in diagnosis, current methods for detecting spinal dysraphism still lack the necessary sensitivity and specificity, driving the pursuit of more effective treatments. The complications, often arising from incomplete spine and brain formation or the exposure of the spinal cord to neurotoxic amniotic fluid, underscore the critical need for prenatal intervention. Current therapeutic approaches remain inadequate, underscoring the urgent need for novel strategies. Tissue engineering, a promising field of medical innovation, holds significant potential for enhancing neural regeneration and repair. Integrating advanced tissue engineering techniques with existing prenatal neurosurgical treatments offers a transformative opportunity to improve outcomes for patients affected by spinal dysraphism.
2024-10-07 | Role of Amniotic Fluid Toxicity in the Pathophysiology of Myelomeningocele: A Narrative Literature Review.
Myelomeningocele is a birth defect whose clinical manifestations are due both to incomplete neural tube closure and the progressive destruction of exposed neuroepithelium during pregnancy. Two hypotheses have been formulated to explain the spinal cord damage in utero: mechanical trauma and chemical factors. The objective of this review was to summarize the current insights about the potential role of amniotic fluid in spinal cord damage in myelomeningocele. Numerous histological and clinical data on animals and humans strongly suggest a progressive degeneration of neural tissue including loss of neural cells, astrogliosis, inflammation, and loss of normal architecture. However, few data have been published about the direct toxicity of amniotic fluid in this neural degeneration, including the potentially toxic effect of meconium. Finally, the chemical and cellular modifications of amniotic fluid composition in myelomeningocele could reflect both the process (toxic effect of meconium) and the consequences of neuroepithelium destruction (release of neural cells). Fetal surgery not only stops the leakage of the cerebrospinal fluid but also reduces the toxic effect of amniotic fluid by restoring the intrauterine environment. Identification of amniotic fluid neurotoxic factors could lead to the development of therapeutic agents designed to protect spinal tissue and improve fetal myelomeningocele outcomes.
2024-06-16 | Intradetrusor botox injection and augmentation cystoplasty trends among spina bifida patients at US freestanding children's hospitals.
Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida. Furthermore, there are little data regarding its use relative to bladder augmentation and patient volume on a national scale. We sought to investigate the contemporary trends of intra-detrusor Botox injection and augment cystoplasty in free-standing children's hospitals. We queried the Pediatric Health Information System database to identify spina bifida patients from 2016 to 2019 who underwent intra-detrusor Botox injection and augment cystoplasty based on CPT and ICD-10 codes. Total spina bifida population under care in the free-standing children's hospitals was estimated by all inpatient and ambulatory surgery encounters as denominators to calculate frequency by time for both intra-detrusor Botox injections and augmentation cystoplasty. In total, we included 1924 intra-detrusor Botox injections and 842 augmentation cystoplasties. 1413 (51.1%) patients were female. Median age at surgery was 10.0 (interquartile range 6.98-13.5) years. There was a significant increase in intra-detrusor Botox injection frequency (p < 0.001). While there was an overall decreasing, but not significant, trend for augmentation cystoplasty, there was a significant increase in this procedure during the summer months compared to the rest of the year (p < 0.001, Figure 1). Sensitivity analysis using only first intra-detrusor Botox injection per patient demonstrated similarly significant increasing trend. Use of intra-detrusor Botox injection for the management of neurogenic bladder has significantly increased among patients with spina bifida while augmentation cystoplasty has slightly decreased, but not significantly. Over time, practice patterns for the treatments of neurogenic bladder among spina bifida children have favored minimally invasive Botox injections while augmentation cystoplasty use has not significantly changed.
gene therapies
2025-12-26 | Congenital Neonatal Synchronous Triple and Dual Neural Tube Defects with Thoracolumbar, Lumbar and Sacral Myelomeningoceles: Two Case Reports
Abstract This manuscript describes two exceptionally rare neonatal presentations of synchronous multiple neural tube defects (NTDs), involving separate thoracolumbar, lumbar, and sacral myelomeningoceles. We report two neonates presenting with synchronous dual and triple, open and closed spinal dysraphisms—distributed across thoracolumbar, lumbar, and sacral regions— without associated cranial defects. Both infants underwent early surgical repair. Case 1 demonstrated favorable early neurological outcomes, while Case 2 exhibited persistent lower‑limb weakness and neurogenic bladder.
2025-10-27 | Adult Type II diastematomyelia with tethered cord and associated spinal anomalies: A case report.
Spinal dysraphism consists a group of congenital anomalies due to defective neural tube closure, among which diastematomyelia or split cord malformation is rare. Split cord malformation is classified into Type I and Type II, with Type II being less common and often asymptomatic. These anomalies may coexist with various spinal anomalies, as tethered cord, neural lipoma, hemimyelocele, and dorsal dermal sinus, forming a complex spectrum. Adult presentations are particularly uncommon and usually incidental. We herein report a 23-year-old male with chronic low back pain and a congenital midline lumbar swelling. Neurological examination and routine investigations were unremarkable. Magnetic resonance imaging revealed Type II diastematomyelia with two hemicords within a single dural sac from L4 to L5, low-lying conus medullaris, hemimyelocele with neural lipoma at L5-S1, tethered cord with filum terminale lipoma extending to S3-S4, and a dorsal dermal sinus tract. Despite the radiological complexity, the patient remained neurologically intact. Neurosurgical intervention was advised; however, the patient chose conservative management with close follow-up. This case highlights a rare adult presentation of complex spinal dysraphism with minimal symptoms. While diastematomyelia Type II is typically diagnosed in childhood, adult cases are infrequent and often delayed. Magnetic resonance imaging is crucial for diagnosis, particularly in asymptomatic individuals with cutaneous markers. Though surgery is generally recommended to prevent neurological decline, conservative management may be appropriate in selected stable cases. This case emphasizes the need to consider spinal anomalies in adults with chronic back pain and the importance of multidisciplinary evaluation.
2025-10-21 | Segmental spinal dysgenesis - a rare type of spinal dysraphism.
Segmental spinal dysgenesis is a rare and complex congenital anomaly that affects the spinal cord. It is hypothesized to be a notochord malformation. Patients generally present with spastic paraparesis and a neurogenic bladder. It is characterized by focal spinal cord dysgenesis and kyphoscoliotic deformity. We present the case of a 2-year-old boy who presented to the outpatient department of our hospital with complaints of recurrent urinary tract infection and fever. On examination, he had bilateral clubfoot, kyphoscoliotic deformity, and paraparesis. Further examination by micturating cystourethrogram revealed bilateral grade V vesico-ureteric reflux. Cystoscopy ruled out a posterior urethral valve. Magnetic resonance imaging of the spine was conducted to evaluate any neurological cause, which revealed a high blunt ending of the spinal cord at the dorsal level 10, with the absence of spinal cord tissue between dorsal 10 and sacral 2 level. Bulky cord-like tissue was noted from the sacral 2-4 level. These findings were associated with a syrinx formation and multiple vertebral malformations. The patient was managed conservatively.
2025-04-24 | A Case Report on Sacral Lipomyelomeningocele
Published on: January 2025 Indian Journal of Pharmacy Practice, 2025; 18(3):333-336. Review Article| doi: 10.5530/ijopp.20250190Authors and affiliation (s): Smitha Sarah Thambi, Angelin Grace Thomas*, Kaushika Saravanan Department of Pharmacy Practice, Swamy Vivekanandha College of Pharmacy, Elayampalayam, Tiruchengode, Namakkal, Tamil Nadu, INDIA. ASTRACT Lipomyelomeningocele (LMMC) is a neural tube defect characterized by the presence of a spinal lipoma that incorporates neural elements, leading to various symptoms like skin lesions, musculoskeletal issues, sensory deficits, and urinary dysfunction. It typically occurs in the lumbosacral region with a prevalence of 0.3-2.5 per 10,000 live births. A 1.4-year-old boy presented with a gradually enlarging swelling on the left lower back since birth, without any skin changes or discharge. Developmentally, he showed delays in mobility and increased urinary frequency compared to his sibling. Neurological examination revealed limb length discrepancy and absent anal wink reflex, suggesting potential tethered cord syndrome. Imaging confirmed a large subcutaneous lipoma with intradural extension at the S1-2 level. The patient underwent L5 to S3 laminectomy and subtotal excision of the lipoma. Postoperative management included dexamethasone and antibiotics. At discharge, he was afebrile, ambulant, and voiding normally, with stable neurological status. LMMC is a significant form of closed spinal dysraphism, often presenting with skin and musculoskeletal signs. Early surgical intervention is crucial for alleviating neurological deficits and preventing complications. This case underscores the importance of awareness and timely treatment in managing spinal dysraphism to optimize long-term outcomes. Keywords: Lipomyelomeningocele, Case report, Neural tube defects, 1.4-year-old boy.
2025-03-07 | Spectrum of neuropathic skeletal injuries in children: a pictorial essay
Neuropathic skeletal injuries in children are common manifestations of conditions associated with sensory impairment. The underlying aetiologies may be rare entities such as congenital insensitivity to pain or more prevalent disorders such as spinal dysraphisms. While the imaging manifestations of such injuries have been described in adults, the paediatric literature is sparse, primarily comprising case reports and case series with insufficient imaging data. Characteristic imaging findings in patients with neuropathic skeletal injuries include neuropathic arthropathy, avascular necrosis, joint dislocation, repeated fractures with exuberant callus formation, epiphyseal separation, and acro-osteolysis. Conventional radiography, MRI, and CT all contribute to the comprehensive assessment of paediatric neuropathic lesions. This pictorial essay illustrates the spectrum of imaging findings in children with neuropathic skeletal injuries of varying aetiologies as well as their natural evolution and treatment. CRITICAL RELEVANCE STATEMENT: This essay addresses a critical gap in the literature on paediatric neuropathic skeletal injuries, providing a detailed overview of their imaging manifestations, natural progression, and relevant treatment strategies, through contemporary imaging techniques such as radiography, MRI, and CT. KEY POINTS: Unrecognised neuropathic skeletal injuries cause progressive permanent deformities, impacting quality of life. Suspect neuropathic arthropathy in children with sensory loss presenting with painless inflamed joints. Neuropathic injuries may be mistaken for osteomyelitis, septic arthritis, or other disorders.
cell therapies
2026-09-11 | Amniotic fluid stem cells alleviate neuronal injury-related changes in spina bifida by inducing autophagy via regulating the FOXO1/STAT3 axis.
Spina bifida (SB) is associated with progressive spinal cord injury and limited therapeutic options for neural protection. Amniotic fluid stem cells (AFSCs) have shown regenerative potential, but their effects on SB-related neuronal injury and the underlying mechanisms remain unclear. In this study, we investigated whether AFSCs alleviate neuronal injury-related changes in SB rats through the modulation of autophagy via the FOXO1/STAT3 pathway. SB-like lesions were induced in neonatal rats, followed by the intramedullary injection of AFSCs or vehicle on postnatal day 1. Behavioral assessment was performed using Basso, Beattie, and Bresnahan locomotor scoring on days 2, 7, and 14 after injection, and lesion-centered lumbosacral spinal cord tissues were collected on day 15. AFSC treatment partially improved hindlimb locomotor scores and reduced neuronal injury-related alterations in SB rats. AFSCs also increased autophagy-associated markers, including LC3II/I and Beclin1, and reduced p62 mRNA expression in vivo and in neural stem cells isolated from SB rats. Mechanistically, AFSC treatment was associated with reduced FOXO1 and enhanced STAT3 signaling. FOXO1 overexpression or STAT3 inhibition attenuated AFSC-mediated effects, whereas siRNA-mediated FOXO1 knockdown enhanced these effects; combined STAT3 knockdown partially reversed the effects of FOXO1 silencing. These findings suggest that AFSCs alleviate SB-related neuronal injury-associated changes by regulating autophagy through the FOXO1/STAT3 axis. This study provides preclinical evidence for an experimental neuroprotective mechanism of AFSCs, although further validation is required before translational applicability can be considered.
2026-07-30 | Transamniotic stem cell therapy (TRASCET).
Transamniotic stem cell therapy (TRASCET) constitutes the least invasive approach to prenatal stem cell delivery described to date. This strategy is largely based on the recently discovered active transport of donor cells from the amniotic fluid to the placenta directly through the amnio-placental interface. From a simple amniocentesis, via the placenta, donor cells of different phenotypes can reach the fetal circulation and virtually any fetal anatomical site, including, and particularly, the fetal bone marrow. As a result, TRASCET has shown broad therapeutic potential in an assortment of animal models. First reported experimentally only a little over a decade ago, it has yet to be attempted clinically, though clinical translation may be imminent. Much of TRASCET's appeal lies in the fact that, in large part, it constitutes a form of replenishment therapy based on the magnification of naturally occurring processes in the distinctive environment of the maternal-fetal unit. Despite significant experimental advances, much promise and perhaps excessive publicity, most cell-based therapies have yet to deliver meaningful large-scale impact to patient care. The few exceptions have been therapies based on the amplification of the normal biological role played by donor cells in their natural environment. TRASCET falls in that category. Further, while fetal stem cells possess unique characteristics when compared with postnatal stem cells, so does the fetus when compared with any other age group, converging into a scenario that enables therapeutic paradigms exclusive to prenatal life. This review summarizes the biological basis, diversity of applications and operability of the TRASCET principle.
2025-10-20 | Urological Congenitalism, Reconstruction and Neuro-Urological Male Patients: Reproductive Health and Fertility Challenges and Their Contemporary Management
Male patients with congenital urogenital anomalies and neuro-urological conditions represent a unique and underrecognized population at risk for infertility and sexual dysfunction. This chapter aims to review the embryological and developmental basis of these conditions and to clarify their direct effects on spermatogenesis, hormonal regulation, and sperm transport. We provide a detailed discussion of common anomalies—including bladder exstrophy, prune belly syndrome, cryptorchidism, and spinal dysraphism—as well as acquired neuro-urological disorders, such as multiple sclerosis, spinal cord injury, and cerebrovascular accident, highlighting their impact on reproductive health and quality of life. Key findings demonstrate that both congenital and neurogenic conditions disrupt male fertility through structural anomalies, impaired testicular development, endocrine dysfunction, and ejaculatory disorders. Contemporary management strategies—ranging from early orchiopexy, reconstructive and substitution phalloplasty, penile prostheses, and urinary tract reconstruction, to assisted reproductive technologies (ART) and sperm retrieval—can mitigate these challenges. Multidisciplinary care, involving functional and reproductive urology, endocrinology, neurology, and psychology, is shown to optimize fertility outcomes. Additionally, models of transitional urology illustrate how proactive fertility counseling and early intervention improve long-term reproductive prospects. In conclusion, congenitalism and neuro-urological disease exert profound effects on male reproductive health that extend beyond childhood survival into adulthood and family planning. Advances in surgical reconstruction, ART, and multidisciplinary care are improving outcomes; yet, long-term follow-up and fertility-preservation strategies remain critical. Future directions—including stem-cell therapy, neuromodulation, and AI-supported management—offer promise in addressing the unmet needs of this vulnerable population.
2025-06-19 | First-In-Human Application of Human Umbilical Cord-Derived Extracellular Vesicles in Tethered Spinal Cord Release Surgery.
Spina bifida is a congenital neural tube defect that has a high risk of secondary neurological deterioration due to tethering of the spinal cord. We present the first application of human umbilical cord-derived mesenchymal stromal cell-derived extracellular vesicle (UC-MSC-EV) therapy in humans during spina bifida surgery. We discuss the application, post-operative outcome and highlight the potential of extracellular vesicle therapy in the management of spina bifida. Administration of extracellular vesicles containing therapeutically active agents has emerged as a potential new treatment modality for neurological disorders. By direct intrathecal application during surgery, UC-MSC-EVs can deliver therapeutic payloads to target cells and the extracellular environment, offering a novel approach to neuroprotection and tissue repair. A 2-year-old girl diagnosed with spina bifida presented with progressive syringomyelia as sign of secondary tethered cord syndrome with intramedullary dermoid inclusion tumour after postnatal spina bifida repair. After pre-operative assessment and multidisciplinary consultation, it was decided to proceed with spinal cord release surgery with the use of EV. During the surgical procedure, the tethered cord was released, dermoid and lipoma tissue were resected. Concurrently, UC-MSC-EVs were administered directly onto the released placode and spinal cord. Post-operative MRI demonstrated a good de-tethering effect and no medullary oedema. No adverse events were reported. The neurological deficit remained unchanged at 6 months follow-up examination. Intraoperative application of UC-MSC-EVs might be an option to ameliorate intrathecal scarring following spina bifida surgery. Whether EVs will result in significant effects for the long-term neurological outcome needs to be studied in randomised clinical trials.
2025-06-07 | Isolation and characterization of human cKIT positive amniotic fluid stem cells obtained from pregnancies with spina bifida.
Myelomeningocele (MMC) and myeloschisis (MS) are considered as the most severe forms of spina bifida aperta characterized by incomplete closure of the neural tube during the first trimester of pregnancy. Open maternal-fetal surgery has been identified as a promising alternative for the repair of MMC/MS. The main goal of this study was the isolation and characterization of stem cells derived from MMC/MS amniotic fluid samples. Human amniotic fluid samples were obtained from pregnant women who underwent surgery for fetal spina bifida repair. We applied fluorescence activated-cell sorting (FACS) to immunoselect stem cells from heterogeneous populations of amniocytes based on cKIT (CD117) expression. The cKIT+ amniocytes were then contrasted with cKIT- and unselected amniocytes in order to characterize the phenotype of these cells. cKIT-expressing amniocytes exhibited spindle-shape morphology, while amniocytes negative for cKIT were round-shaped. qRT-PCR analysis revealed significant upregulation of mean mRNA levels of KIT and CD90 genes and downregulation of CK8 gene in cKIT-expressing amniocytes, compared to the negative and unsorted cells. The expression of pluripotency antigens was comparable in sorted cKIT+ and cKIT- amniocytes and in unselected cells. Our results are of pivotal importance for the future application of amniotic fluid derived stem cells in spina bidfida repair.
other
2024-11-20 | Day-to-day variations and effects of urinary and fecal incontinence among adults with spina bifida: An ecological momentary assessment diary pilot study.
No studies have evaluated the day-to-day variations in urinary incontinence (UI) and fecal incontinence (FI) among adults with spina bifida (SB). We aimed to 1) describe variations in UI/FI over 30 days, 2) assess factors associated with anxiety about incontinence, and 3) correlate anxiety about incontinence and health-related quality of life (HRQOL) among adults with SB (exploratory). Adults with SB participated in a larger 30-day smartphone-based ecological momentary assessment (EMA) study of well-being and incontinence. We analyzed baseline demographics, temporal variables (baseline UI/FI, incontinence, and anxiety on days prior), and incontinence episode-specific variables (number of daily episodes, incontinence interval, quantity). Urinary and fecal incontinence-related anxiety (UIA/FIA) was measured on a 5-point Likert scale ("How anxious were you because of urine/stool leaks today?"), HRQOL with QUALAS-A (scores range 0-100, 0 = lowest HRQOL). Mixed-effects, random intercept ordinal and linear regression was used. Eighty-nine adults participated at a median age of 33 years old (71 % female, 53 % shunted, 49 % community ambulators). Participants contributed 2578 total diary days: 61 % were associated with any incontinence (41 % UI only, 6 % FI only, 13 % both). Eighty-two (92 %) adults reported UI on a median of 16 days, but experiences varied: 6 % had a single episode, while 33 % had UI on 28-30 days (Summary Figure). Seventy adults (79 %) reported FI on a median of 5 days, less frequently than UI (p < 0.001), but experiences varied: 11 % had a single FI episode, while 31 % had FI on 10 or more days. Fewer participants reported any UIA than FIA (50 % vs. 72 %, respectively, p < 0.001). On multivariate regression, (1) higher UIA was reported by individuals with higher baseline UIA, higher UIA on days prior, multiple daily episodes and higher UI quantity (p ≤ 0.02), while (2) higher FIA was reported by those with lower baseline HRQOL, fewer FI episodes on days prior, higher FIA on days prior, and higher UI quantity (p ≤ 0.02). FIA was correlated with lower end-of-study HRQOL (p = 0.03). Instances of incontinence are not uniform experiences. Their effects vary with factors beyond the actual episode. This suggests novel potential points of intervention to improving long-term HRQOL among people with incontinence. Day-to-day experiences of UI and FI vary among adults with SB across multiple dimensions. Anxiety about incontinence when it occurs varies not only based on individual- and episode-specific characteristics, but also on incontinence in the preceding days. Operationalizing these insights into potential clinical interventions warrants further investigation.
2022-03-23 | Fetal and Perinatal Expression Profiles of Proinflammatory Cytokines in the Neuroplacodes of Rats with Myelomeningoceles: A Contribution to the Understanding of Secondary Spinal Cord Injury in Open Spinal Dysraphism.
The cellular and molecular mechanisms that presumably underlie the progressive functional decline of the myelomeningocele (MMC) placode are not well understood. We previously identified key players in post-traumatic spinal cord injury cascades in human MMC tissues obtained during postnatal repair. In this study, we conducted experiments to further investigate these mediators in the prenatal time course under standardized conditions in a retinoic acid-induced MMC rat model. A retinoic acid MMC model was established using time-dated Sprague-Dawley rats, which were gavage-fed with all-trans retinoic acid (RA; 60 mg/kg) dissolved in olive oil at E10. Control animals received olive oil only. Fetuses from both groups were obtained at E16, E18, and E22. The spinal cords (SCs) of both groups were formalin-fixed or snap-frozen. Tissues were screened by real-time reverse transcription polymerase chain reaction for the expression of cytokines and chemokines known to play a role in the lesion cascades of the central nervous system after trauma. MMC placodes exhibited inflammatory cells and glial activation in the later gestational stages. At the messenger RNA (mRNA) level, interleukin-1 beta, tumor necrosis factor alpha, and tumor necrosis factor receptor type 1 exhibited significant induction at E22. interleukin-1 beta receptor type 1 mRNA was induced significantly at E16 and E22. Double labeling experiments confirmed the co-staining of these cytokines and their receptors with ionized calcium-binding adapter molecule 1 (i.e., inflammatory cells), vimentin, and nestin in different anatomical SC areas and neuronal nuclear protein in ventral horn neurons. C-X-C motif chemokine 12 mRNA was elevated in control and MMC animals at E16 compared with E18 and E22. C-X3-C motif ligand 1 mRNA was lower in MMC tissues than in control tissues on E16. The presented findings contribute to the concept that pathophysiological mechanisms, such as cytokine induction in the neuroplacode, in addition to the "first hit," promote secondary spinal cord injury with functional loss in the late fetal time course. Further, these mediators should be taken into consideration in the development of new therapeutic approaches for open spinal dysraphism.
2018-06-15 | A trauma-informed approach supports health and development in children and youth with spina bifida.
Children with developmental disabilities may be at greater risk for experiencing maltreatment and traumatic events, threats to their physical and psychological safety and well-being. Young children and youth with spina bifida benefit from being considered in light of this risk, and may be especially vulnerable given the complexity of their neurodevelopmental condition. A trauma-informed approach brings together evidence from the neurosciences, epidemiology and psychology to promote improved developmental, behavioral, physical and mental health status. Incorporating a trauma-informed approach strengthens a longitudinal, interdisciplinary and developmentally-oriented care model for children and youth with spina bifida. A case example further illustrates how using a trauma-informed approach and evidence-based interventions can foster the development and well-being of youth with spina bifida who have been impacted by a traumatic event.
2009-05-14 | Latex allergy: two educational cases.
Natural rubber latex (NRL) allergy is a significant problem both for health care workers and for children with complex medical and surgical conditions that require multiple surgical interventions. Primary and secondary prophylaxis are effective measures in identified high risk groups, such as spina bifida (SB). It is therefore likely that with proper attention to prevention and secondary prophylaxis in the highest risk groups that the numbers of paediatric SB patients with NRL allergy will continue to decrease. In contrast medical awareness of established latex allergy needs to be maintained. The issue of latex sensitisation via fruit and food allergy will also remain, so some of the attention that SB patients have received in the past may need to be refocussed onto other emerging high risk groups. Innovative immunomodulatory approaches may soon translate to the clinic for latex sensitised or allergic subjects.
small molecules
2026-07-01 | Bioinformatics-based prediction and in vitro validation of quercetin’s potential targets in congenital spinal deformity: An exploratory study on its role in osteogenic differentiation
Background Congenital spinal deformities (CSDs) are a class of complex spinal malformations arising from abnormal vertebral development, often associated with aberrant osteogenic differentiation. Quercetin (QUE), a natural flavonoid compound, possesses potent osteogenic properties; however, its specific therapeutic targets and molecular mechanisms in CSDs remain unclear. Objective This study aimed to identify the potential targets of QUE in CSDs treatment and elucidate its regulatory role in osteogenic differentiation. Methods Differentially expressed genes (DEGs) between placental tissues from fetuses with isolated spina bifida and normal controls were identified using the GSE252552 dataset. QUE-associated targets were retrieved from the SwissTargetPrediction database. Intersecting targets were analyzed via protein-protein interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Key modules and genes were systematically screened using weighted gene co-expression network analysis (WGCNA). Machine learning algorithms were employed to identify hub genes. Molecular docking was performed to verify binding affinity. In vitro experiments using human mesenchymal stem cells (hMSCs) were conducted to validate the regulatory effects of QUE on the identified target and osteogenic differentiation. Results A total of 5835 DEGs were identified, and 31 intersecting targets with QUE were obtained. Functional enrichment analyses indicated that these targets were primarily involved in the PI3K-Akt and FoxO signaling pathways. WGCNA identified 1485 module genes significantly correlated with CSDs, yielding 10 intersecting hub genes. Through machine learning screening, Aurora kinase B (AURKB) was identified as the pivotal target. Bioinformatics analysis revealed that AURKB was upregulated in CSD tissues and progressively increased during the osteogenic differentiation of hMSCs. Molecular docking confirmed a strong binding affinity between QUE and AURKB. In vitro experiments demonstrated that QUE treatment promoted hMSC viability and upregulated AURKB protein expression in a dose-dependent manner. Mechanistically, QUE enhanced alkaline phosphatase (ALP) activity, increased mineralized nodule formation, and upregulated osteogenic markers (BMP2 and RUNX2). However, these osteogenic-promoting effects were significantly attenuated by AURKB knockdown. Conclusion This study identified AURKB as a critical target of QUE in CSDs. QUE promoted osteogenic differentiation in hMSCs by upregulating AURKB expression.
2026-04-27 | Anesthetic Management of a Parturient With Lipomyelomeningocele and Tethered Cord for Cesarean Section.
Lipomyelomeningocele (LMMC) presents significant anesthetic challenges due to spinal cord tethering and distorted anatomy, which make the gold-standard neuraxial anesthesia technically difficult and neurologically risky. We report the case of a 29-year-old primigravida with LMMC and prior neurosurgeries scheduled for an elective cesarean section. Given the risk of direct neural injury and unpredictable block spread, a planned general anesthesia (GA) was performed, and a multimodal analgesic strategy was employed. The procedure was uneventful, resulting in a healthy neonate and a mother with excellent pain control and no deviation from her neurological baseline. This case demonstrates that while neuraxial techniques are usually preferred, GA is a safe and necessary alternative for patients with complex spinal dysraphism. Success requires a thorough preoperative neurological assessment, neuroimaging review, and tailored multidisciplinary approach.
2026-04-14 | Advancements in the Treatment and Management of Voiding Dysfunction in Individuals with Spina Bifida.
PURPOSE OF REVIEW: This manuscript aims to provide an overview of the pathophysiology of voiding dysfunction, management goals, and treatment options for individuals with spina bifida in order to better assist providers caring for these patients and their families. RECENT FINDINGS: Recent studies have demonstrated efficacy and safety of beta-3 agonists and onabotulinum toxin A as noninvasive options for management of neurogenic lower urinary tract dysfunction. Studies focusing on patient reported outcomes and health-related quality of life have raised greater awareness of patient goals and socio-environmental factors in the counseling of different treatment options. This review highlights the latest research on the management of voiding dysfunction in patients living with spina bifida. Better understanding of pathophysiology and new developments in non-invasive treatment options have substantially improved long-term durability and outlook for these patients. Future research should aim to identify patient and family goals to better manage expectations and quality of life for this lifelong condition.
2026-02-05 | Cerebrospinal fluid matrix-remodeling biomarkers in neonates with myelomeningocele: MMP-9, TIMP-1, and TGF-β1 expression.
Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases, regulate extracellular matrix remodeling and neural tissue homeostasis. Transforming growth factor β1 modulates inflammation, ECM deposition, and tissue repair. Dysregulation of these pathways may contribute to congenital spinal dysraphism. This study quantified cerebrospinal fluid MMP-9, TIMP-1, and TGF-β1 in neonates with myelomeningocele and evaluated their potential as pathogenic mediators or biomarkers. Preoperative CSF samples were collected from 48 neonates with isolated myelomeningocele (Group 1) and 24 age-matched controls with sterile CSF (Group 2). MMP-9, TIMP-1, and TGF-β1 concentrations were measured via ELISA. Intergroup differences were analyzed, and Pearson correlation assessed relationships among biomarkers. CSF MMP-9 levels were significantly elevated in neonates with myelomeningocele compared to controls (57.12 ± 64.19 ng/mL vs. 11.29 ± 6.79 ng/mL; p < 0.05). TIMP-1 (368.78 ± 220.08 ng/mL vs. 450.04 ± 390.22 ng/mL) and TGF-β1 (2.32 ± 1.44 ng/mL vs. 2.524 ± 1.07 ng/mL) did not differ significantly. MMP-9 correlated positively with TIMP-1 across all subjects (p < 0.05) and with TGF-β1 within the myelomeningocele group (p < 0.05), indicating coordinated regulation of ECM degradation and fibrogenic signaling. Elevated CSF MMP-9 in neonates with myelomeningocele suggests dysregulated ECM remodeling may be associated with neural tube malformation. MMP-9 may serve as a biomarker of ECM dysregulation, providing insights into the pathogenesis of congenital spinal dysraphism and identifying possible targets for future therapeutic interventions.
2025-11-13 | Blood Pressure Optimization During Fetoscopic Repair of Open Spinal Dysraphism: Insights from Advanced Hemodynamic Monitoring
Background/Objectives: Fetoscopic repair of open spinal dysraphism (OSD) is a rare intrauterine procedure performed in specialized fetal surgery centers. Conducted under restrictive fluid management and continuous tocolysis, it poses substantial challenges to maternal hemodynamic stability. Blood pressure optimization with vasopressor boluses is often required, yet intraoperative hemodynamic data remain limited. Methods: This prospective observational study was conducted between December 2023 and January 2025 during fetoscopic repair of OSD at Marburg University Hospital, Germany. Maternal hemodynamics were continuously monitored using pulse contour analysis with the Acumen IQ sensor and HemoSphere platform (Edwards Lifesciences, Irvine, CA, USA). To stabilize arterial pressure, cafedrine/theodrenaline (Akrinor, Ratiopharm, Ulm, Germany) was administered as intravenous boluses. Hemodynamic parameters were analyzed immediately before and after each bolus. Fetal heart rate was assessed as a secondary parameter at predefined intraoperative time points when available. Results: A total of 13 patients and 110 vasopressor boluses were analyzed. Reported values reflect median percent changes; parentheses indicate the total range. Following maternal blood pressure optimization, mean arterial pressure increased by 13.7% (5.9–21.6), systemic vascular resistance index by 23.1% (8.3–36.7), and dP/dtmax by 21.7% (6.3–29.9): p < 0.001 for all. Cardiac index and stroke volume index decreased by −6.7% (−11.8 to −0.6), p < 0.001, and −4.3% (−9.8 to 1.8), p = 0.048, respectively. Fetal heart rate remained stable (+0.4% (−0.8 to 1.5); p = 0.470). A total of 38 HPI alerts were followed by hypotension, with a median latency of 120 s (80–235); 73 alerts were not followed by hypotension during the observation period. Conclusions: Intermittent cafedrine/theodrenaline boluses significantly increased arterial pressure, dP/dtmax, and systemic vascular resistance under conditions of fluid restriction and tocolysis-induced vasodilation. Maternal heart rate remained stable, and cardiac output showed only minor reductions. Fetal heart rate was unchanged following maternal blood pressure treatment, indicating no adverse fetal response to C/T within the observed intraoperative period.
proteins
2026-06-30 | Healthcare utilization in patients with spina bifida and bone fractures.
To compare bone fractures and fracture-related healthcare costs in individuals with and without spina bifida (SB). This is a retrospective observational trial. California's Healthcare Access and Information database was utilized to identify all individuals with SB who sought care in California emergency departments, inpatient hospitals, or ambulatory surgery centres between 2005 and 2017. Bone fracture encounters and associated healthcare utilization factors were compared among individuals with spina bifida vs individuals without spina bifida, matched 5:1 by birth year. Between 2005 and 2017, 20,290 individuals with spina bifida sought care in California emergency departments, inpatient hospitals, or ambulatory surgery centres. Compared with 101,450 individuals in the comparison group, those with spina bifida were more likely to seek care for a bone fracture (OR 1.64, p < 0.001) and more likely to sustain repeat fractures (36% vs 26%, p < 0.001). Individuals with spina bifida sustained more bone fractures per capita at each body location studied, with more than double the fractures per capita at the chest (2.0x), foot (2.1x), pelvis (2.4x), leg (2.5x), and vertebrae (2.5x). Individuals with spina bifida spent more cumulative days hospitalized for bone fractures (mean 9.4 vs 7.6, p < 0.001). Individuals with spina bifida were diagnosed with more bone fractures per capita than age-matched persons without spina bifida.
2025-11-17 | Neuroprotective properties of erythropoietin (Epo) and its receptor (EpoR) in open spinal dysraphism (OSD): an investigation of EpoR expression in a rat OSD model, along with in vitro studies on the neuroprotective effects of Epo on rat spinal cord-derived neural progenitor cells.
Research into treatment options that complement surgery for open spinal dysraphism (OSD) is necessary to further improve outcomes following prenatal or postnatal surgery. We investigated erythropoietin (Epo) and its receptor (EpoR) as a potential neuroprotective agent and target in OSD. Epo- and EpoR-expression was examined on mRNA and immunohistochemical level in neuroplacodes obtained from a rat retinoic acid-induced OSD model at E16, E18, E22. Neural progenitor cells (NPCs) derived from spinal cords of adult Long Evans rats were exposed to varying concentrations of human artificial amniotic fluid (aAF). Cytotoxicity assays were conducted to assess the impact of aAF exposure, with and without Epo. The influence of Epo on NPC's cellular marker expression was analyzed using qRT-PCR. EpoR mRNA expression was elevated significantly on E18 and E22 in OSD- compared to control tissue. EpoR immunoreactivity exhibited consistent expression in ventral and dorsal horns, central canal, and ganglia. It co-stained with Hif-2α, β-III-tubulin, NeuN, and Musashi1. Exposure of NPCs to aAF reduced proliferation and increased death rates dose-dependently. Adding Epo significantly counteracted antiproliferative and cytotoxic aAF effects on NPCs, resulting in similar or lower death rates than those observed in untreated controls. Exposure of NPCs to aAF reduced their expression of neuronal markers. Adding Epo restored their differentiation capacities. Induction of EpoR in neuroplacodes, its co-staining with neuronal and NPC markers, and the neuroprotective effects of Epo on aAF-treated NPCs in vitro establish Epo as a promising candidate for neuroprotective therapies that can supplement surgical measures for OSD.
2024-12-04 | Advanced Tissue-Engineering Approaches for Prenatal Neurosurgical Management of Spinal Dysraphism
Spinal dysraphism arises from neural tube closure defects occurring between 2 and 6 weeks of gestation, leading to severe complications after birth. It is typically classified as either open or closed, depending on whether the defect is covered by skin. Despite advances in diagnosis, current methods for detecting spinal dysraphism still lack the necessary sensitivity and specificity, driving the pursuit of more effective treatments. The complications, often arising from incomplete spine and brain formation or the exposure of the spinal cord to neurotoxic amniotic fluid, underscore the critical need for prenatal intervention. Current therapeutic approaches remain inadequate, underscoring the urgent need for novel strategies. Tissue engineering, a promising field of medical innovation, holds significant potential for enhancing neural regeneration and repair. Integrating advanced tissue engineering techniques with existing prenatal neurosurgical treatments offers a transformative opportunity to improve outcomes for patients affected by spinal dysraphism.
2024-10-07 | Role of Amniotic Fluid Toxicity in the Pathophysiology of Myelomeningocele: A Narrative Literature Review.
Myelomeningocele is a birth defect whose clinical manifestations are due both to incomplete neural tube closure and the progressive destruction of exposed neuroepithelium during pregnancy. Two hypotheses have been formulated to explain the spinal cord damage in utero: mechanical trauma and chemical factors. The objective of this review was to summarize the current insights about the potential role of amniotic fluid in spinal cord damage in myelomeningocele. Numerous histological and clinical data on animals and humans strongly suggest a progressive degeneration of neural tissue including loss of neural cells, astrogliosis, inflammation, and loss of normal architecture. However, few data have been published about the direct toxicity of amniotic fluid in this neural degeneration, including the potentially toxic effect of meconium. Finally, the chemical and cellular modifications of amniotic fluid composition in myelomeningocele could reflect both the process (toxic effect of meconium) and the consequences of neuroepithelium destruction (release of neural cells). Fetal surgery not only stops the leakage of the cerebrospinal fluid but also reduces the toxic effect of amniotic fluid by restoring the intrauterine environment. Identification of amniotic fluid neurotoxic factors could lead to the development of therapeutic agents designed to protect spinal tissue and improve fetal myelomeningocele outcomes.
2024-06-16 | Intradetrusor botox injection and augmentation cystoplasty trends among spina bifida patients at US freestanding children's hospitals.
Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida. Furthermore, there are little data regarding its use relative to bladder augmentation and patient volume on a national scale. We sought to investigate the contemporary trends of intra-detrusor Botox injection and augment cystoplasty in free-standing children's hospitals. We queried the Pediatric Health Information System database to identify spina bifida patients from 2016 to 2019 who underwent intra-detrusor Botox injection and augment cystoplasty based on CPT and ICD-10 codes. Total spina bifida population under care in the free-standing children's hospitals was estimated by all inpatient and ambulatory surgery encounters as denominators to calculate frequency by time for both intra-detrusor Botox injections and augmentation cystoplasty. In total, we included 1924 intra-detrusor Botox injections and 842 augmentation cystoplasties. 1413 (51.1%) patients were female. Median age at surgery was 10.0 (interquartile range 6.98-13.5) years. There was a significant increase in intra-detrusor Botox injection frequency (p < 0.001). While there was an overall decreasing, but not significant, trend for augmentation cystoplasty, there was a significant increase in this procedure during the summer months compared to the rest of the year (p < 0.001, Figure 1). Sensitivity analysis using only first intra-detrusor Botox injection per patient demonstrated similarly significant increasing trend. Use of intra-detrusor Botox injection for the management of neurogenic bladder has significantly increased among patients with spina bifida while augmentation cystoplasty has slightly decreased, but not significantly. Over time, practice patterns for the treatments of neurogenic bladder among spina bifida children have favored minimally invasive Botox injections while augmentation cystoplasty use has not significantly changed.
gene therapies
2025-12-26 | Congenital Neonatal Synchronous Triple and Dual Neural Tube Defects with Thoracolumbar, Lumbar and Sacral Myelomeningoceles: Two Case Reports
Abstract This manuscript describes two exceptionally rare neonatal presentations of synchronous multiple neural tube defects (NTDs), involving separate thoracolumbar, lumbar, and sacral myelomeningoceles. We report two neonates presenting with synchronous dual and triple, open and closed spinal dysraphisms—distributed across thoracolumbar, lumbar, and sacral regions— without associated cranial defects. Both infants underwent early surgical repair. Case 1 demonstrated favorable early neurological outcomes, while Case 2 exhibited persistent lower‑limb weakness and neurogenic bladder.
2025-10-27 | Adult Type II diastematomyelia with tethered cord and associated spinal anomalies: A case report.
Spinal dysraphism consists a group of congenital anomalies due to defective neural tube closure, among which diastematomyelia or split cord malformation is rare. Split cord malformation is classified into Type I and Type II, with Type II being less common and often asymptomatic. These anomalies may coexist with various spinal anomalies, as tethered cord, neural lipoma, hemimyelocele, and dorsal dermal sinus, forming a complex spectrum. Adult presentations are particularly uncommon and usually incidental. We herein report a 23-year-old male with chronic low back pain and a congenital midline lumbar swelling. Neurological examination and routine investigations were unremarkable. Magnetic resonance imaging revealed Type II diastematomyelia with two hemicords within a single dural sac from L4 to L5, low-lying conus medullaris, hemimyelocele with neural lipoma at L5-S1, tethered cord with filum terminale lipoma extending to S3-S4, and a dorsal dermal sinus tract. Despite the radiological complexity, the patient remained neurologically intact. Neurosurgical intervention was advised; however, the patient chose conservative management with close follow-up. This case highlights a rare adult presentation of complex spinal dysraphism with minimal symptoms. While diastematomyelia Type II is typically diagnosed in childhood, adult cases are infrequent and often delayed. Magnetic resonance imaging is crucial for diagnosis, particularly in asymptomatic individuals with cutaneous markers. Though surgery is generally recommended to prevent neurological decline, conservative management may be appropriate in selected stable cases. This case emphasizes the need to consider spinal anomalies in adults with chronic back pain and the importance of multidisciplinary evaluation.
2025-10-21 | Segmental spinal dysgenesis - a rare type of spinal dysraphism.
Segmental spinal dysgenesis is a rare and complex congenital anomaly that affects the spinal cord. It is hypothesized to be a notochord malformation. Patients generally present with spastic paraparesis and a neurogenic bladder. It is characterized by focal spinal cord dysgenesis and kyphoscoliotic deformity. We present the case of a 2-year-old boy who presented to the outpatient department of our hospital with complaints of recurrent urinary tract infection and fever. On examination, he had bilateral clubfoot, kyphoscoliotic deformity, and paraparesis. Further examination by micturating cystourethrogram revealed bilateral grade V vesico-ureteric reflux. Cystoscopy ruled out a posterior urethral valve. Magnetic resonance imaging of the spine was conducted to evaluate any neurological cause, which revealed a high blunt ending of the spinal cord at the dorsal level 10, with the absence of spinal cord tissue between dorsal 10 and sacral 2 level. Bulky cord-like tissue was noted from the sacral 2-4 level. These findings were associated with a syrinx formation and multiple vertebral malformations. The patient was managed conservatively.
2025-04-24 | A Case Report on Sacral Lipomyelomeningocele
Published on: January 2025 Indian Journal of Pharmacy Practice, 2025; 18(3):333-336. Review Article| doi: 10.5530/ijopp.20250190Authors and affiliation (s): Smitha Sarah Thambi, Angelin Grace Thomas*, Kaushika Saravanan Department of Pharmacy Practice, Swamy Vivekanandha College of Pharmacy, Elayampalayam, Tiruchengode, Namakkal, Tamil Nadu, INDIA. ASTRACT Lipomyelomeningocele (LMMC) is a neural tube defect characterized by the presence of a spinal lipoma that incorporates neural elements, leading to various symptoms like skin lesions, musculoskeletal issues, sensory deficits, and urinary dysfunction. It typically occurs in the lumbosacral region with a prevalence of 0.3-2.5 per 10,000 live births. A 1.4-year-old boy presented with a gradually enlarging swelling on the left lower back since birth, without any skin changes or discharge. Developmentally, he showed delays in mobility and increased urinary frequency compared to his sibling. Neurological examination revealed limb length discrepancy and absent anal wink reflex, suggesting potential tethered cord syndrome. Imaging confirmed a large subcutaneous lipoma with intradural extension at the S1-2 level. The patient underwent L5 to S3 laminectomy and subtotal excision of the lipoma. Postoperative management included dexamethasone and antibiotics. At discharge, he was afebrile, ambulant, and voiding normally, with stable neurological status. LMMC is a significant form of closed spinal dysraphism, often presenting with skin and musculoskeletal signs. Early surgical intervention is crucial for alleviating neurological deficits and preventing complications. This case underscores the importance of awareness and timely treatment in managing spinal dysraphism to optimize long-term outcomes. Keywords: Lipomyelomeningocele, Case report, Neural tube defects, 1.4-year-old boy.
2025-03-07 | Spectrum of neuropathic skeletal injuries in children: a pictorial essay
Neuropathic skeletal injuries in children are common manifestations of conditions associated with sensory impairment. The underlying aetiologies may be rare entities such as congenital insensitivity to pain or more prevalent disorders such as spinal dysraphisms. While the imaging manifestations of such injuries have been described in adults, the paediatric literature is sparse, primarily comprising case reports and case series with insufficient imaging data. Characteristic imaging findings in patients with neuropathic skeletal injuries include neuropathic arthropathy, avascular necrosis, joint dislocation, repeated fractures with exuberant callus formation, epiphyseal separation, and acro-osteolysis. Conventional radiography, MRI, and CT all contribute to the comprehensive assessment of paediatric neuropathic lesions. This pictorial essay illustrates the spectrum of imaging findings in children with neuropathic skeletal injuries of varying aetiologies as well as their natural evolution and treatment. CRITICAL RELEVANCE STATEMENT: This essay addresses a critical gap in the literature on paediatric neuropathic skeletal injuries, providing a detailed overview of their imaging manifestations, natural progression, and relevant treatment strategies, through contemporary imaging techniques such as radiography, MRI, and CT. KEY POINTS: Unrecognised neuropathic skeletal injuries cause progressive permanent deformities, impacting quality of life. Suspect neuropathic arthropathy in children with sensory loss presenting with painless inflamed joints. Neuropathic injuries may be mistaken for osteomyelitis, septic arthritis, or other disorders.
cell therapies
2026-09-11 | Amniotic fluid stem cells alleviate neuronal injury-related changes in spina bifida by inducing autophagy via regulating the FOXO1/STAT3 axis.
Spina bifida (SB) is associated with progressive spinal cord injury and limited therapeutic options for neural protection. Amniotic fluid stem cells (AFSCs) have shown regenerative potential, but their effects on SB-related neuronal injury and the underlying mechanisms remain unclear. In this study, we investigated whether AFSCs alleviate neuronal injury-related changes in SB rats through the modulation of autophagy via the FOXO1/STAT3 pathway. SB-like lesions were induced in neonatal rats, followed by the intramedullary injection of AFSCs or vehicle on postnatal day 1. Behavioral assessment was performed using Basso, Beattie, and Bresnahan locomotor scoring on days 2, 7, and 14 after injection, and lesion-centered lumbosacral spinal cord tissues were collected on day 15. AFSC treatment partially improved hindlimb locomotor scores and reduced neuronal injury-related alterations in SB rats. AFSCs also increased autophagy-associated markers, including LC3II/I and Beclin1, and reduced p62 mRNA expression in vivo and in neural stem cells isolated from SB rats. Mechanistically, AFSC treatment was associated with reduced FOXO1 and enhanced STAT3 signaling. FOXO1 overexpression or STAT3 inhibition attenuated AFSC-mediated effects, whereas siRNA-mediated FOXO1 knockdown enhanced these effects; combined STAT3 knockdown partially reversed the effects of FOXO1 silencing. These findings suggest that AFSCs alleviate SB-related neuronal injury-associated changes by regulating autophagy through the FOXO1/STAT3 axis. This study provides preclinical evidence for an experimental neuroprotective mechanism of AFSCs, although further validation is required before translational applicability can be considered.
2026-07-30 | Transamniotic stem cell therapy (TRASCET).
Transamniotic stem cell therapy (TRASCET) constitutes the least invasive approach to prenatal stem cell delivery described to date. This strategy is largely based on the recently discovered active transport of donor cells from the amniotic fluid to the placenta directly through the amnio-placental interface. From a simple amniocentesis, via the placenta, donor cells of different phenotypes can reach the fetal circulation and virtually any fetal anatomical site, including, and particularly, the fetal bone marrow. As a result, TRASCET has shown broad therapeutic potential in an assortment of animal models. First reported experimentally only a little over a decade ago, it has yet to be attempted clinically, though clinical translation may be imminent. Much of TRASCET's appeal lies in the fact that, in large part, it constitutes a form of replenishment therapy based on the magnification of naturally occurring processes in the distinctive environment of the maternal-fetal unit. Despite significant experimental advances, much promise and perhaps excessive publicity, most cell-based therapies have yet to deliver meaningful large-scale impact to patient care. The few exceptions have been therapies based on the amplification of the normal biological role played by donor cells in their natural environment. TRASCET falls in that category. Further, while fetal stem cells possess unique characteristics when compared with postnatal stem cells, so does the fetus when compared with any other age group, converging into a scenario that enables therapeutic paradigms exclusive to prenatal life. This review summarizes the biological basis, diversity of applications and operability of the TRASCET principle.
2025-10-20 | Urological Congenitalism, Reconstruction and Neuro-Urological Male Patients: Reproductive Health and Fertility Challenges and Their Contemporary Management
Male patients with congenital urogenital anomalies and neuro-urological conditions represent a unique and underrecognized population at risk for infertility and sexual dysfunction. This chapter aims to review the embryological and developmental basis of these conditions and to clarify their direct effects on spermatogenesis, hormonal regulation, and sperm transport. We provide a detailed discussion of common anomalies—including bladder exstrophy, prune belly syndrome, cryptorchidism, and spinal dysraphism—as well as acquired neuro-urological disorders, such as multiple sclerosis, spinal cord injury, and cerebrovascular accident, highlighting their impact on reproductive health and quality of life. Key findings demonstrate that both congenital and neurogenic conditions disrupt male fertility through structural anomalies, impaired testicular development, endocrine dysfunction, and ejaculatory disorders. Contemporary management strategies—ranging from early orchiopexy, reconstructive and substitution phalloplasty, penile prostheses, and urinary tract reconstruction, to assisted reproductive technologies (ART) and sperm retrieval—can mitigate these challenges. Multidisciplinary care, involving functional and reproductive urology, endocrinology, neurology, and psychology, is shown to optimize fertility outcomes. Additionally, models of transitional urology illustrate how proactive fertility counseling and early intervention improve long-term reproductive prospects. In conclusion, congenitalism and neuro-urological disease exert profound effects on male reproductive health that extend beyond childhood survival into adulthood and family planning. Advances in surgical reconstruction, ART, and multidisciplinary care are improving outcomes; yet, long-term follow-up and fertility-preservation strategies remain critical. Future directions—including stem-cell therapy, neuromodulation, and AI-supported management—offer promise in addressing the unmet needs of this vulnerable population.
2025-06-19 | First-In-Human Application of Human Umbilical Cord-Derived Extracellular Vesicles in Tethered Spinal Cord Release Surgery.
Spina bifida is a congenital neural tube defect that has a high risk of secondary neurological deterioration due to tethering of the spinal cord. We present the first application of human umbilical cord-derived mesenchymal stromal cell-derived extracellular vesicle (UC-MSC-EV) therapy in humans during spina bifida surgery. We discuss the application, post-operative outcome and highlight the potential of extracellular vesicle therapy in the management of spina bifida. Administration of extracellular vesicles containing therapeutically active agents has emerged as a potential new treatment modality for neurological disorders. By direct intrathecal application during surgery, UC-MSC-EVs can deliver therapeutic payloads to target cells and the extracellular environment, offering a novel approach to neuroprotection and tissue repair. A 2-year-old girl diagnosed with spina bifida presented with progressive syringomyelia as sign of secondary tethered cord syndrome with intramedullary dermoid inclusion tumour after postnatal spina bifida repair. After pre-operative assessment and multidisciplinary consultation, it was decided to proceed with spinal cord release surgery with the use of EV. During the surgical procedure, the tethered cord was released, dermoid and lipoma tissue were resected. Concurrently, UC-MSC-EVs were administered directly onto the released placode and spinal cord. Post-operative MRI demonstrated a good de-tethering effect and no medullary oedema. No adverse events were reported. The neurological deficit remained unchanged at 6 months follow-up examination. Intraoperative application of UC-MSC-EVs might be an option to ameliorate intrathecal scarring following spina bifida surgery. Whether EVs will result in significant effects for the long-term neurological outcome needs to be studied in randomised clinical trials.
2025-06-07 | Isolation and characterization of human cKIT positive amniotic fluid stem cells obtained from pregnancies with spina bifida.
Myelomeningocele (MMC) and myeloschisis (MS) are considered as the most severe forms of spina bifida aperta characterized by incomplete closure of the neural tube during the first trimester of pregnancy. Open maternal-fetal surgery has been identified as a promising alternative for the repair of MMC/MS. The main goal of this study was the isolation and characterization of stem cells derived from MMC/MS amniotic fluid samples. Human amniotic fluid samples were obtained from pregnant women who underwent surgery for fetal spina bifida repair. We applied fluorescence activated-cell sorting (FACS) to immunoselect stem cells from heterogeneous populations of amniocytes based on cKIT (CD117) expression. The cKIT+ amniocytes were then contrasted with cKIT- and unselected amniocytes in order to characterize the phenotype of these cells. cKIT-expressing amniocytes exhibited spindle-shape morphology, while amniocytes negative for cKIT were round-shaped. qRT-PCR analysis revealed significant upregulation of mean mRNA levels of KIT and CD90 genes and downregulation of CK8 gene in cKIT-expressing amniocytes, compared to the negative and unsorted cells. The expression of pluripotency antigens was comparable in sorted cKIT+ and cKIT- amniocytes and in unselected cells. Our results are of pivotal importance for the future application of amniotic fluid derived stem cells in spina bidfida repair.
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2024-11-20 | Day-to-day variations and effects of urinary and fecal incontinence among adults with spina bifida: An ecological momentary assessment diary pilot study.
No studies have evaluated the day-to-day variations in urinary incontinence (UI) and fecal incontinence (FI) among adults with spina bifida (SB). We aimed to 1) describe variations in UI/FI over 30 days, 2) assess factors associated with anxiety about incontinence, and 3) correlate anxiety about incontinence and health-related quality of life (HRQOL) among adults with SB (exploratory). Adults with SB participated in a larger 30-day smartphone-based ecological momentary assessment (EMA) study of well-being and incontinence. We analyzed baseline demographics, temporal variables (baseline UI/FI, incontinence, and anxiety on days prior), and incontinence episode-specific variables (number of daily episodes, incontinence interval, quantity). Urinary and fecal incontinence-related anxiety (UIA/FIA) was measured on a 5-point Likert scale ("How anxious were you because of urine/stool leaks today?"), HRQOL with QUALAS-A (scores range 0-100, 0 = lowest HRQOL). Mixed-effects, random intercept ordinal and linear regression was used. Eighty-nine adults participated at a median age of 33 years old (71 % female, 53 % shunted, 49 % community ambulators). Participants contributed 2578 total diary days: 61 % were associated with any incontinence (41 % UI only, 6 % FI only, 13 % both). Eighty-two (92 %) adults reported UI on a median of 16 days, but experiences varied: 6 % had a single episode, while 33 % had UI on 28-30 days (Summary Figure). Seventy adults (79 %) reported FI on a median of 5 days, less frequently than UI (p < 0.001), but experiences varied: 11 % had a single FI episode, while 31 % had FI on 10 or more days. Fewer participants reported any UIA than FIA (50 % vs. 72 %, respectively, p < 0.001). On multivariate regression, (1) higher UIA was reported by individuals with higher baseline UIA, higher UIA on days prior, multiple daily episodes and higher UI quantity (p ≤ 0.02), while (2) higher FIA was reported by those with lower baseline HRQOL, fewer FI episodes on days prior, higher FIA on days prior, and higher UI quantity (p ≤ 0.02). FIA was correlated with lower end-of-study HRQOL (p = 0.03). Instances of incontinence are not uniform experiences. Their effects vary with factors beyond the actual episode. This suggests novel potential points of intervention to improving long-term HRQOL among people with incontinence. Day-to-day experiences of UI and FI vary among adults with SB across multiple dimensions. Anxiety about incontinence when it occurs varies not only based on individual- and episode-specific characteristics, but also on incontinence in the preceding days. Operationalizing these insights into potential clinical interventions warrants further investigation.
2022-03-23 | Fetal and Perinatal Expression Profiles of Proinflammatory Cytokines in the Neuroplacodes of Rats with Myelomeningoceles: A Contribution to the Understanding of Secondary Spinal Cord Injury in Open Spinal Dysraphism.
The cellular and molecular mechanisms that presumably underlie the progressive functional decline of the myelomeningocele (MMC) placode are not well understood. We previously identified key players in post-traumatic spinal cord injury cascades in human MMC tissues obtained during postnatal repair. In this study, we conducted experiments to further investigate these mediators in the prenatal time course under standardized conditions in a retinoic acid-induced MMC rat model. A retinoic acid MMC model was established using time-dated Sprague-Dawley rats, which were gavage-fed with all-trans retinoic acid (RA; 60 mg/kg) dissolved in olive oil at E10. Control animals received olive oil only. Fetuses from both groups were obtained at E16, E18, and E22. The spinal cords (SCs) of both groups were formalin-fixed or snap-frozen. Tissues were screened by real-time reverse transcription polymerase chain reaction for the expression of cytokines and chemokines known to play a role in the lesion cascades of the central nervous system after trauma. MMC placodes exhibited inflammatory cells and glial activation in the later gestational stages. At the messenger RNA (mRNA) level, interleukin-1 beta, tumor necrosis factor alpha, and tumor necrosis factor receptor type 1 exhibited significant induction at E22. interleukin-1 beta receptor type 1 mRNA was induced significantly at E16 and E22. Double labeling experiments confirmed the co-staining of these cytokines and their receptors with ionized calcium-binding adapter molecule 1 (i.e., inflammatory cells), vimentin, and nestin in different anatomical SC areas and neuronal nuclear protein in ventral horn neurons. C-X-C motif chemokine 12 mRNA was elevated in control and MMC animals at E16 compared with E18 and E22. C-X3-C motif ligand 1 mRNA was lower in MMC tissues than in control tissues on E16. The presented findings contribute to the concept that pathophysiological mechanisms, such as cytokine induction in the neuroplacode, in addition to the "first hit," promote secondary spinal cord injury with functional loss in the late fetal time course. Further, these mediators should be taken into consideration in the development of new therapeutic approaches for open spinal dysraphism.
2018-06-15 | A trauma-informed approach supports health and development in children and youth with spina bifida.
Children with developmental disabilities may be at greater risk for experiencing maltreatment and traumatic events, threats to their physical and psychological safety and well-being. Young children and youth with spina bifida benefit from being considered in light of this risk, and may be especially vulnerable given the complexity of their neurodevelopmental condition. A trauma-informed approach brings together evidence from the neurosciences, epidemiology and psychology to promote improved developmental, behavioral, physical and mental health status. Incorporating a trauma-informed approach strengthens a longitudinal, interdisciplinary and developmentally-oriented care model for children and youth with spina bifida. A case example further illustrates how using a trauma-informed approach and evidence-based interventions can foster the development and well-being of youth with spina bifida who have been impacted by a traumatic event.
2009-05-14 | Latex allergy: two educational cases.
Natural rubber latex (NRL) allergy is a significant problem both for health care workers and for children with complex medical and surgical conditions that require multiple surgical interventions. Primary and secondary prophylaxis are effective measures in identified high risk groups, such as spina bifida (SB). It is therefore likely that with proper attention to prevention and secondary prophylaxis in the highest risk groups that the numbers of paediatric SB patients with NRL allergy will continue to decrease. In contrast medical awareness of established latex allergy needs to be maintained. The issue of latex sensitisation via fruit and food allergy will also remain, so some of the attention that SB patients have received in the past may need to be refocussed onto other emerging high risk groups. Innovative immunomodulatory approaches may soon translate to the clinic for latex sensitised or allergic subjects.
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Drug Discovery Landscape
3 orphan drug designations for Spina bifida and other spinal dysraphisms.
3 orphan drug designations for Spina bifida and other spinal dysraphisms.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Allogeneic, early gestational, placenta-derived mesenchymal stem cells (PMSC) | cell therapies | FDA | — | Diana Farmer, MD |
cryopreserved human umbilical cord | cell therapies | FDA | — | TissueTech, Inc. |
Autologous smooth muscles cells, Autologous urothelial cells | cell therapies | EMA | Emas Pharma Limited |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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