RARE DISEASE
Distal spinal muscular atrophy type 3
Distal spinal muscular atrophy type 3
Distal spinal muscular atrophy type 3
Synonyms: Autosomal recessive distal spinal muscular atrophy type 3, Distal hereditary motor neuropathy type 3 and type 4, dHMN3 and dHMN4, dSMA3
Synonyms: Autosomal recessive distal spinal muscular atrophy type 3, Distal hereditary motor neuropathy type 3 and type 4, dHMN3 and dHMN4, dSMA3
Synonyms: Autosomal recessive distal spinal muscular atrophy type 3, Distal hereditary motor neuropathy type 3 and type 4, dHMN3 and dHMN4, dSMA3
Drug discovery
0
drugs
With orphan designations
Overview
Distal spinal muscular atrophy type 3 (dSMA3) is a rare genetic neuromuscular disorder characterized by progressive distal limb weakness and atrophy, later involving proximal muscles and respiratory function. It encompasses two distinct subtypes: autosomal recessive dSMA3 (linked to variants in genes like BSCL2 or GARS1) and X-linked dSMA3 (caused by ATP7A mutations). Onset ranges from infancy to adulthood, with symptoms including gait impairment, tremors, and diaphragmatic dysfunction in advanced stages [1][6][17].
Therapies
Supportive care: Physical/occupational therapy, orthotics, and respiratory support to preserve mobility and function [3][10][18].
Symptom management: Bracing for contractures, assistive devices (wheelchairs, ventilators) [4][17].
Research focus: Neuroprotective agents and neuromuscular junction-targeting therapies in preclinical trials [13].
Categories: rare genetic diseases, rare neurological diseases
Research Papers
160 drug discovery papers about Distal spinal muscular atrophy type 3, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
160 drug discovery papers about Distal spinal muscular atrophy type 3, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2025-01-21 | Difficulty of administration of nusinersen in complex-column spinal muscular atrophy: New alternative technique by means of cervical intrathecal access through an Ommaya reservoir.
The study aimed to describe a new Ommaya reservoir implantation method in late-onset SMA patients, assessing its safety and effectiveness under standard clinical conditions. Prospective observational study. Lumbar intrathecal access was unfeasible due to significant scoliosis and prior spinal surgeries with instrumentation. Patients were infused with Nusinersen through the Ommaya reservoir at Hospital Universitario La Paz (Spain) following the standard dosing protocol. The cohort was composed of 6 patients, 5 individuals with type 2 SMA (83.3 %), and 1 patient presenting with type 3 SMA. 4 of the patients were functionally sitters (66.7 %) and 2 had lost this ability prior to initiating treatment (non-sitters). Mean treatment was 34.7 months. Patient discharge was done in all the cases within 48 h post-admission; no significant postoperative complications or during administration of nusinersen were reported. Functional progress was observed in all patients. Hammersmith Functional Motor Scale Expanded (HFMSE) showed a low average increase (1.0), attributed to the severity of baseline functional impairments. Improvements in upper extremity motor function, measured by the Revised Upper Limb Module (RULM), were more pronounced, with an average improvement of 3.3. Disability levels as measured by the Egen Klassifikation 2 (EK2) scale, declined by 4.4. the current study broadens knowledge regarding the efficacy and safety of using an Ommaya reservoir to administer nusinersen in patients with SMA Types 2 and 3. The technique demonstrated rapid, straightforward drug delivery through a subcutaneous needle, maintaining optimal sterility without radiation or the need for a multidisciplinary team.
2025-01-21 | Effect of nusinersen on pulmonary function in children with spinal muscular atrophy in the plateau region: A pilot study.
The drug nusinersen is applied to improve motor function in patients with spinal muscle atrophy (SMA). However, research on the effects of this treatment on lung function is lacking. To investigate the effect of nusinersen on lung function in children with SMA in the Plateau. A total of 20 patients with SMA (types 1, 2, or 3) who started nusinersen treatment at the Department of Pediatrics at Yunnan First People's Hospital from March 2022 and February 2024 were studied. A retrospective study was conducted to investigate changes in lung function parameters (including forced vital capacity, forced expiratory volume at 1 s, forced expiratory volume at 1 s/forced vital capacity, and peak expiratory flow) in patients with SMA treated with nusinersen. 20 patients (13 male, 7 female; aged 5-16 years) were enrolled, including 2, 9, and 9 with SMA types 1, 2, and 3, respectively. The mean value of FVC % and FEV1/FVC % did not decrease further following nusinersen treatment in any patients. The mean value of FEV1% was 4.4 % and 5.0 % higher than before treatment in all patients (P = 0.03), and those with type 2 SMA (P = 0.04), respectively. The overall mean PEF % did not decrease any further after treatment. However, the average level in the type 2 group increased by 2.9 % (P = 0.03). Patients with SMA, particularly those classified as type 2, showed a trend of improvement in lung function following nusinersen treatment.
2025-01-13 | Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.
Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.5-21 kg. SMART was an open-label, multicenter, phase 3b study conducted across 13 sites in 9 countries (NCT04851873). Symptomatic pediatric participants with SMA (any type; treatment-naïve or had discontinued prior treatment) were stratified into 3 weight cohorts (≥8.5-13, >13-17, and >17-21 kg), administered onasemnogene abeparvovec, and followed for 52 weeks. Corticosteroids were initiated 24 hours before infusion with dose increases in response to adverse events (AEs) and subsequent tapering at investigator discretion. The primary objective was safety. Secondary objective was efficacy (motor function/motor milestones). Twenty-four participants were enrolled; the majority had SMA type 2 (n = 11), 3 SMN2 copies (n = 18), and prior treatment (n = 21). All participants completed the study; no deaths occurred. All participants had ≥1 treatment-related AE(s), 7 of 24 (29%) had serious treatment-related AEs, and 23 of 24 (96%) had ≥1 AE of special interest. Twenty of 24 participants (83%) had asymptomatic hepatotoxicity events, which were primarily transaminase elevations. No participant had bilirubin elevations >2× upper limit of normal, developed symptomatic hepatotoxicity, or met Hy law criteria. Transient asymptomatic thrombocytopenia events were reported in 17 of 24 participants (71%); all resolved spontaneously with no related bleeding events reported. Three of 24 participants (13%) had cardiac AEs (all unrelated to treatment). No thrombotic microangiopathy or dorsal root ganglionopathy-related AEs were reported. AE frequency and severity were similar across weight groups, although corticosteroid exposure was greater for the 2 heavier cohorts (median 135.0, 201.0, and 194.0 days, respectively) with 37% and 33% still on corticosteroids at the study end. By week 52, most participants maintained or improved motor function (Hammersmith Functional Motor Scale-Expanded 16/18; Revised Upper Limb Module 15/17); 4 participants (all 3 SMN2 copies) achieved new motor milestones. Onasemnogene abeparvovec safety profile was similar across weight groups in this heterogenous participant population. Frequency and duration of asymptomatic aminotransferase elevations and thrombocytopenia are notable findings. Most participants demonstrated maintenance or improvement of motor function, suggesting clinical benefit for patients with SMA weighing up to 21 kg. ClinicalTrials.gov identifier (NCT04851873, clinicaltrials.gov/study/NCT04851873) submitted April 19, 2021. First participant enrolled on September 8, 2021. This study provides Class IV evidence that intravenous onasemnogene abeparvovec is safe in pediatric patients with SMA who weigh 8.5-21 kg.
2025-01-21 | Difficulty of administration of nusinersen in complex-column spinal muscular atrophy: New alternative technique by means of cervical intrathecal access through an Ommaya reservoir.
The study aimed to describe a new Ommaya reservoir implantation method in late-onset SMA patients, assessing its safety and effectiveness under standard clinical conditions. Prospective observational study. Lumbar intrathecal access was unfeasible due to significant scoliosis and prior spinal surgeries with instrumentation. Patients were infused with Nusinersen through the Ommaya reservoir at Hospital Universitario La Paz (Spain) following the standard dosing protocol. The cohort was composed of 6 patients, 5 individuals with type 2 SMA (83.3 %), and 1 patient presenting with type 3 SMA. 4 of the patients were functionally sitters (66.7 %) and 2 had lost this ability prior to initiating treatment (non-sitters). Mean treatment was 34.7 months. Patient discharge was done in all the cases within 48 h post-admission; no significant postoperative complications or during administration of nusinersen were reported. Functional progress was observed in all patients. Hammersmith Functional Motor Scale Expanded (HFMSE) showed a low average increase (1.0), attributed to the severity of baseline functional impairments. Improvements in upper extremity motor function, measured by the Revised Upper Limb Module (RULM), were more pronounced, with an average improvement of 3.3. Disability levels as measured by the Egen Klassifikation 2 (EK2) scale, declined by 4.4. the current study broadens knowledge regarding the efficacy and safety of using an Ommaya reservoir to administer nusinersen in patients with SMA Types 2 and 3. The technique demonstrated rapid, straightforward drug delivery through a subcutaneous needle, maintaining optimal sterility without radiation or the need for a multidisciplinary team.
2025-01-21 | Effect of nusinersen on pulmonary function in children with spinal muscular atrophy in the plateau region: A pilot study.
The drug nusinersen is applied to improve motor function in patients with spinal muscle atrophy (SMA). However, research on the effects of this treatment on lung function is lacking. To investigate the effect of nusinersen on lung function in children with SMA in the Plateau. A total of 20 patients with SMA (types 1, 2, or 3) who started nusinersen treatment at the Department of Pediatrics at Yunnan First People's Hospital from March 2022 and February 2024 were studied. A retrospective study was conducted to investigate changes in lung function parameters (including forced vital capacity, forced expiratory volume at 1 s, forced expiratory volume at 1 s/forced vital capacity, and peak expiratory flow) in patients with SMA treated with nusinersen. 20 patients (13 male, 7 female; aged 5-16 years) were enrolled, including 2, 9, and 9 with SMA types 1, 2, and 3, respectively. The mean value of FVC % and FEV1/FVC % did not decrease further following nusinersen treatment in any patients. The mean value of FEV1% was 4.4 % and 5.0 % higher than before treatment in all patients (P = 0.03), and those with type 2 SMA (P = 0.04), respectively. The overall mean PEF % did not decrease any further after treatment. However, the average level in the type 2 group increased by 2.9 % (P = 0.03). Patients with SMA, particularly those classified as type 2, showed a trend of improvement in lung function following nusinersen treatment.
2025-01-13 | Safety and Efficacy of IV Onasemnogene Abeparvovec for Pediatric Patients With Spinal Muscular Atrophy: The Phase 3b SMART Study.
Safety and efficacy of IV onasemnogene abeparvovec has been demonstrated for patients with spinal muscular atrophy (SMA) weighing <8.5 kg. SMART was the first clinical trial to evaluate onasemnogene abeparvovec for participants weighing 8.5-21 kg. SMART was an open-label, multicenter, phase 3b study conducted across 13 sites in 9 countries (NCT04851873). Symptomatic pediatric participants with SMA (any type; treatment-naïve or had discontinued prior treatment) were stratified into 3 weight cohorts (≥8.5-13, >13-17, and >17-21 kg), administered onasemnogene abeparvovec, and followed for 52 weeks. Corticosteroids were initiated 24 hours before infusion with dose increases in response to adverse events (AEs) and subsequent tapering at investigator discretion. The primary objective was safety. Secondary objective was efficacy (motor function/motor milestones). Twenty-four participants were enrolled; the majority had SMA type 2 (n = 11), 3 SMN2 copies (n = 18), and prior treatment (n = 21). All participants completed the study; no deaths occurred. All participants had ≥1 treatment-related AE(s), 7 of 24 (29%) had serious treatment-related AEs, and 23 of 24 (96%) had ≥1 AE of special interest. Twenty of 24 participants (83%) had asymptomatic hepatotoxicity events, which were primarily transaminase elevations. No participant had bilirubin elevations >2× upper limit of normal, developed symptomatic hepatotoxicity, or met Hy law criteria. Transient asymptomatic thrombocytopenia events were reported in 17 of 24 participants (71%); all resolved spontaneously with no related bleeding events reported. Three of 24 participants (13%) had cardiac AEs (all unrelated to treatment). No thrombotic microangiopathy or dorsal root ganglionopathy-related AEs were reported. AE frequency and severity were similar across weight groups, although corticosteroid exposure was greater for the 2 heavier cohorts (median 135.0, 201.0, and 194.0 days, respectively) with 37% and 33% still on corticosteroids at the study end. By week 52, most participants maintained or improved motor function (Hammersmith Functional Motor Scale-Expanded 16/18; Revised Upper Limb Module 15/17); 4 participants (all 3 SMN2 copies) achieved new motor milestones. Onasemnogene abeparvovec safety profile was similar across weight groups in this heterogenous participant population. Frequency and duration of asymptomatic aminotransferase elevations and thrombocytopenia are notable findings. Most participants demonstrated maintenance or improvement of motor function, suggesting clinical benefit for patients with SMA weighing up to 21 kg. ClinicalTrials.gov identifier (NCT04851873, clinicaltrials.gov/study/NCT04851873) submitted April 19, 2021. First participant enrolled on September 8, 2021. This study provides Class IV evidence that intravenous onasemnogene abeparvovec is safe in pediatric patients with SMA who weigh 8.5-21 kg.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.