RARE DISEASE
Alpers-Huttenlocher syndrome
Alpers-Huttenlocher syndrome
Alpers-Huttenlocher syndrome
Synonyms: Alpers progressive sclerosing poliodystrophy, Alpers syndrome, Progressive neuronal degeneration of childhood with liver disease
Synonyms: Alpers progressive sclerosing poliodystrophy, Alpers syndrome, Progressive neuronal degeneration of childhood with liver disease
Synonyms: Alpers progressive sclerosing poliodystrophy, Alpers syndrome, Progressive neuronal degeneration of childhood with liver disease
Drug discovery
1
drug
With orphan designation
Overview
Alpers-Huttenlocher syndrome (AHS) is a rare, autosomal recessive mitochondrial disorder caused by POLG gene mutations, leading to mitochondrial DNA depletion. It is characterized by a triad of intractable epilepsy, psychomotor regression, and hepatopathy, with episodic exacerbations triggered by infections or medications like valproic acid. Onset is typically in early childhood (2–4 years) or adolescence, progressing to fatal liver failure or neurologic decline. Diagnosis involves clinical criteria, neuroimaging (occipital lobe atrophy), and POLG confirmation. No cure exists; management focuses on seizure control and palliative care [1][5][9][16].
Burden
Fatal progression: Median survival 3 months–12 years post-diagnosis [1][6][15][17].
Multisystem involvement: Seizures, liver failure, GI dysmotility, and optic atrophy necessitate intensive care [1][6][9].
High care demands: 24/7 monitoring, frequent hospitalizations, and complex end-of-life decisions [9][14][17].
Therapies
Antiseizure agents: Avoid valproic acid (hepatotoxic); use levetiracetam, lamotrigine, or benzodiazepines [1][3][15].
Palliative care: Nutritional support (gastrostomy tubes), respiratory interventions, and physical/occupational therapy [3][14][15].
Adjunctive measures: Ketogenic diet (reduces refractory seizures) [7][15], antioxidants, and infection prevention [3][9].
Categories: rare genetic diseases, rare hepatic diseases, rare inborn errors of metabolism, rare neurological diseases
Research Papers
43 drug discovery papers about Alpers-Huttenlocher syndrome, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
43 drug discovery papers about Alpers-Huttenlocher syndrome, with 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2024-08-02 | Safety and efficacy of deoxycytidine/deoxythymidine combination therapy in POLG-related disorders: 6-month interim results of an open-label, single arm, phase 2 trial.
DNA polymerase gamma (POLG)-related disorders are a group of rare neurodegenerative mitochondrial diseases caused by pathogenic variants in POLG, the gene encoding POLG. Patients may experience a range of signs and symptoms, including seizures, vision loss, myopathy, neuropathy, developmental impairment or regression, and liver failure. The diseases follow a progressive, degenerative course, with most affected individuals dying within 3 months-12 years of diagnosis. At present, there are no effective treatments for POLG-related disorders. In this study we report the interim 6-month data from a long term open-label, single arm phase 2 trial, in which we assessed the safety and efficacy of combination therapy with deoxycytidine and deoxythymidine (dC/dT) in children with POLG-related disorders. dC/dT was given enterally in powder form, dissolved in water. The primary outcome measures included Newcastle Mitochondrial Disease Scale (NMDS) score, serum growth differentiation factor 15 (GDF-15; a biomarker of mitochondrial dysfunction), electroencephalography (EEG), seizure diary, and blood and urine tests to assess end organ and mitochondrial function. Secondary outcome measures included recording of all adverse events to evaluate the safety of the intervention. The trial is registered with ClinicalTrials.gov, NCT04802707 (https://clinicaltrials.gov/ct2/show/NCT04802707). Data were collected from 14 October, 2021 to 13 December, 2023. We present 6-month interim data from the first ten people with POLG-related disorders enrolled in the trial, six with Alpers-Huttenlocher syndrome, two with ataxia-neuropathy spectrum, and two who do not fit into a classical POLG-related phenotype. During the 6 months of treatment, NMDS score improved from a mean of 27.3 at baseline to 20.7 at 6 months (estimated difference 6.0; 95% CI 2.5-∞). GDF-15 values remained stable or decreased in all patients; the mean decreased from 1031 pg/ml to 729 pg/ml (estimated difference 200; 95% CI 12-∞). 8/10 patients had abnormal baseline EEG; improvement in EEG was seen in 5 of these 8. There were no significant changes in other blood and urine testing. Regarding adverse events, two patients experienced diarrhea that spontaneously resolved. dC/dT is a promising treatment option for people with POLG-related disorders. Further research is needed to assess the long-term safety and efficacy in POLG-related disorders, as well as safety and efficacy in other mitochondrial DNA depletion disorders. This study was primarily funded by the Liam Foundation, with additional funding from the Savoy Foundation, Grand Défi Pierre Lavoie Foundation, and Fonds de Recherche du Québec - Santé.
2024-04-02 | Nucleoside supplements as treatments for mitochondrial DNA depletion syndrome
Introduction: In mitochondrial DNA (mtDNA) depletion syndrome (MDS), patients cannot maintain sufficient mtDNA for their energy needs. MDS presentations range from infantile encephalopathy with hepatopathy (Alpers syndrome) to adult chronic progressive external ophthalmoplegia. Most are caused by nucleotide imbalance or by defects in the mtDNA replisome. There is currently no curative treatment available. Nucleoside therapy is a promising experimental treatment for TK2 deficiency, where patients are supplemented with exogenous deoxypyrimidines. We aimed to explore the benefits of nucleoside supplementation in POLG and TWNK deficient fibroblasts. Methods: We used high-content fluorescence microscopy with software-based image analysis to assay mtDNA content and membrane potential quantitatively, using vital dyes PicoGreen and MitoTracker Red CMXRos respectively. We tested the effect of 15 combinations (A, T, G, C, AT, AC, AG, CT, CG, GT, ATC, ATG, AGC, TGC, ATGC) of deoxynucleoside supplements on mtDNA content of fibroblasts derived from four patients with MDS (POLG1, POLG2, DGUOK, TWNK) in both a replicating (10% dialysed FCS) and quiescent (0.1% dialysed FCS) state. We used qPCR to measure mtDNA content of supplemented and non-supplemented fibroblasts following mtDNA depletion using 20 µM ddC and after 14- and 21-day recovery in a quiescent state. Results: Nucleoside treatments at 200 µM that significantly increased mtDNA content also significantly reduced the number of cells remaining in culture after 7 days of treatment, as well as mitochondrial membrane potential. These toxic effects were abolished by reducing the concentration of nucleosides to 50 µM. In POLG1 and TWNK cells the combination of ATGC treatment increased mtDNA content the most after 7 days in non-replicating cells. ATGC nucleoside combination significantly increased the rate of mtDNA recovery in quiescent POLG1 cells following mtDNA depletion by ddC. Conclusion: High-content imaging enabled us to link mtDNA copy number with key read-outs linked to patient wellbeing. Elevated G increased mtDNA copy number but severely impaired fibroblast growth, potentially by inhibiting purine synthesis and/or causing replication stress. Combinations of nucleosides ATGC, T, or TC, benefited growth of cells harbouring POLG mutations. These combinations, one of which reflects a commercially available preparation, could be explored further for treatment of POLG patients.
2018-03-05 | Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy.
Mitochondrial dysfunction manifests as different neurological diseases, but the mechanisms underlying the clinical variability remain poorly understood. To clarify whether different brain cells have differential sensitivity to mitochondrial dysfunction, we induced mitochondrial DNA (mtDNA) depletion in either neurons or astrocytes of mice, by inactivating Twinkle (TwKO), the replicative mtDNA helicase. Here we show that astrocytes, the most abundant cerebral cell type, are chronically activated upon mtDNA loss, leading to early-onset spongiotic degeneration of brain parenchyma, microgliosis and secondary neurodegeneration. Neuronal mtDNA loss does not, however, cause symptoms until 8 months of age. Findings in astrocyte-TwKO mimic neuropathology of Alpers syndrome, infantile-onset mitochondrial spongiotic encephalopathy caused by mtDNA maintenance defects. Our evidence indicates that (1) astrocytes are dependent on mtDNA integrity; (2) mitochondrial metabolism contributes to their activation; (3) chronic astrocyte activation has devastating consequences, underlying spongiotic encephalopathy; and that (4) astrocytes are a potential target for interventions.
2015-10-01 | An approach to epilepsy in mitochondrial disorders of childhood
Mitochondrial epilepsy is commonly seen in certain mtDNA mutations such as mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) and myoclonic epilepsy with ragged red fibres (MERRF) syndromes. They are also seen with mutations in the mtDNA maintenance gene polymerase gamma (POLG) which may manifest with Alpers or Alpers-Huttenlocher syndrome, mitochondrial recessive ataxia syndrome (MIRAS), spinocerebellar ataxia with epilepsy (SCAE), and myoclonus, epilepsy, myopathy, sensory ataxia (MEMSA) syndromes. They are also seen in disorders of Coenzyme Q10 biosynthesis, Complex 1 deficiency and disorders of mitochondrial translation such as with RARS2 gene mutations. The mechanisms for the epileptogenesis may relate to impaired mitochondrial sequestration of calcium, decreased intracellular ATP generation, increased glutamate release into synaptic clefts, increased reactive oxygen species arising from defects in Complex I and Complex III of the respiratory chain, and "stroke-like episodes" as seen in MELAS syndrome. Mitochondrial epilepsy may be characterized by generalized, focal, multifocal or myoclonic seizures in semiology and is critical to control given the further exacerbation of the bioenergetic insufficiency by the heightened energy requirement of seizing neurons. Treatment often consists of a combination of multiple standard anticonvulsants along with vitamins, cofactors, antioxidants and electron donors to enhance mitochondrial function which may be only partially successful. The ketogenic diet is promising but warrants prospective clinical trials. It is important to try to avoid use of mitochondrial toxins such as valproic acid which also exacerbates cellular carnitine deficiency requiring supplementation and which has been associated with rapid neurodegeneration and liver failure in Alpers-Huttenlocher disease.
2012-04-09 | The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders
Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.
cell therapies
2026-03-01 | 1399: SUCCESSFUL MANAGEMENT OF ADULT ALPERS-HUTTENLOCHER SYNDROME WITH MANAGEMENT VIA OLT
Introduction: Alpers-Huttenlocher syndrome (AHS) is a rare congenital mitochondrial disease caused by deletions in polymerase gamma (POLG) gene. It typically presents in childhood with seizures and liver failure, but adult-onset cases are exceedingly rare and diagnostically challenging. Liver transplantation has historically been avoided due to concerns over continued neurologic deterioration. We present a critically ill adult with known AHS and acute liver failure managed successfully with orthotopic liver transplantation (OLT) in the ICU. Description: A 21-year-old woman with genetically confirmed AHS due to biallelic pathogenic POLG variants presented to the ICU with new-onset refractory status epilepticus, persistent hypoglycemia, coagulopathy, and acute liver failure. She required vasopressor support and continuous renal replacement therapy for hepatorenal syndrome. Valproate had been recently initiated, and liver biopsy suggested both drug-induced liver injury and underlying disease progression. Her MELD-Na was 31 on admission. Despite her critical state, she was evaluated and approved by a multidisciplinary transplant team. She underwent deceased donor OLT on ICU day three. Her postoperative course was notable for resolution of hepatic dysfunction and resolution of her status epilepticus, although she continued to experience residual seizures and psychomotor symptoms. Discussion: AHS in adults is exceptionally rare, with estimates suggesting fewer than one case per two million individuals. This case highlights the complexity of managing acute liver failure in a critically ill patient with underlying AHS. Valproate can unmask or accelerate hepatic failure in POLG-related disease, typically recognized only once critical decompensation has occurred. While OLT has been considered contraindicated in AHS due to ongoing neurologic decline, this case illustrates that in selected patients, transplant during active multiorgan failure may be lifesaving. Although conclusions cannot be drawn from a single case, this report underscores the need for early recognition, multidisciplinary coordination, and individualized decision-making in the ICU when managing rare mitochondrial syndromes.
small molecules
2024-08-02 | Safety and efficacy of deoxycytidine/deoxythymidine combination therapy in POLG-related disorders: 6-month interim results of an open-label, single arm, phase 2 trial.
DNA polymerase gamma (POLG)-related disorders are a group of rare neurodegenerative mitochondrial diseases caused by pathogenic variants in POLG, the gene encoding POLG. Patients may experience a range of signs and symptoms, including seizures, vision loss, myopathy, neuropathy, developmental impairment or regression, and liver failure. The diseases follow a progressive, degenerative course, with most affected individuals dying within 3 months-12 years of diagnosis. At present, there are no effective treatments for POLG-related disorders. In this study we report the interim 6-month data from a long term open-label, single arm phase 2 trial, in which we assessed the safety and efficacy of combination therapy with deoxycytidine and deoxythymidine (dC/dT) in children with POLG-related disorders. dC/dT was given enterally in powder form, dissolved in water. The primary outcome measures included Newcastle Mitochondrial Disease Scale (NMDS) score, serum growth differentiation factor 15 (GDF-15; a biomarker of mitochondrial dysfunction), electroencephalography (EEG), seizure diary, and blood and urine tests to assess end organ and mitochondrial function. Secondary outcome measures included recording of all adverse events to evaluate the safety of the intervention. The trial is registered with ClinicalTrials.gov, NCT04802707 (https://clinicaltrials.gov/ct2/show/NCT04802707). Data were collected from 14 October, 2021 to 13 December, 2023. We present 6-month interim data from the first ten people with POLG-related disorders enrolled in the trial, six with Alpers-Huttenlocher syndrome, two with ataxia-neuropathy spectrum, and two who do not fit into a classical POLG-related phenotype. During the 6 months of treatment, NMDS score improved from a mean of 27.3 at baseline to 20.7 at 6 months (estimated difference 6.0; 95% CI 2.5-∞). GDF-15 values remained stable or decreased in all patients; the mean decreased from 1031 pg/ml to 729 pg/ml (estimated difference 200; 95% CI 12-∞). 8/10 patients had abnormal baseline EEG; improvement in EEG was seen in 5 of these 8. There were no significant changes in other blood and urine testing. Regarding adverse events, two patients experienced diarrhea that spontaneously resolved. dC/dT is a promising treatment option for people with POLG-related disorders. Further research is needed to assess the long-term safety and efficacy in POLG-related disorders, as well as safety and efficacy in other mitochondrial DNA depletion disorders. This study was primarily funded by the Liam Foundation, with additional funding from the Savoy Foundation, Grand Défi Pierre Lavoie Foundation, and Fonds de Recherche du Québec - Santé.
2024-04-02 | Nucleoside supplements as treatments for mitochondrial DNA depletion syndrome
Introduction: In mitochondrial DNA (mtDNA) depletion syndrome (MDS), patients cannot maintain sufficient mtDNA for their energy needs. MDS presentations range from infantile encephalopathy with hepatopathy (Alpers syndrome) to adult chronic progressive external ophthalmoplegia. Most are caused by nucleotide imbalance or by defects in the mtDNA replisome. There is currently no curative treatment available. Nucleoside therapy is a promising experimental treatment for TK2 deficiency, where patients are supplemented with exogenous deoxypyrimidines. We aimed to explore the benefits of nucleoside supplementation in POLG and TWNK deficient fibroblasts. Methods: We used high-content fluorescence microscopy with software-based image analysis to assay mtDNA content and membrane potential quantitatively, using vital dyes PicoGreen and MitoTracker Red CMXRos respectively. We tested the effect of 15 combinations (A, T, G, C, AT, AC, AG, CT, CG, GT, ATC, ATG, AGC, TGC, ATGC) of deoxynucleoside supplements on mtDNA content of fibroblasts derived from four patients with MDS (POLG1, POLG2, DGUOK, TWNK) in both a replicating (10% dialysed FCS) and quiescent (0.1% dialysed FCS) state. We used qPCR to measure mtDNA content of supplemented and non-supplemented fibroblasts following mtDNA depletion using 20 µM ddC and after 14- and 21-day recovery in a quiescent state. Results: Nucleoside treatments at 200 µM that significantly increased mtDNA content also significantly reduced the number of cells remaining in culture after 7 days of treatment, as well as mitochondrial membrane potential. These toxic effects were abolished by reducing the concentration of nucleosides to 50 µM. In POLG1 and TWNK cells the combination of ATGC treatment increased mtDNA content the most after 7 days in non-replicating cells. ATGC nucleoside combination significantly increased the rate of mtDNA recovery in quiescent POLG1 cells following mtDNA depletion by ddC. Conclusion: High-content imaging enabled us to link mtDNA copy number with key read-outs linked to patient wellbeing. Elevated G increased mtDNA copy number but severely impaired fibroblast growth, potentially by inhibiting purine synthesis and/or causing replication stress. Combinations of nucleosides ATGC, T, or TC, benefited growth of cells harbouring POLG mutations. These combinations, one of which reflects a commercially available preparation, could be explored further for treatment of POLG patients.
2018-03-05 | Loss of mtDNA activates astrocytes and leads to spongiotic encephalopathy.
Mitochondrial dysfunction manifests as different neurological diseases, but the mechanisms underlying the clinical variability remain poorly understood. To clarify whether different brain cells have differential sensitivity to mitochondrial dysfunction, we induced mitochondrial DNA (mtDNA) depletion in either neurons or astrocytes of mice, by inactivating Twinkle (TwKO), the replicative mtDNA helicase. Here we show that astrocytes, the most abundant cerebral cell type, are chronically activated upon mtDNA loss, leading to early-onset spongiotic degeneration of brain parenchyma, microgliosis and secondary neurodegeneration. Neuronal mtDNA loss does not, however, cause symptoms until 8 months of age. Findings in astrocyte-TwKO mimic neuropathology of Alpers syndrome, infantile-onset mitochondrial spongiotic encephalopathy caused by mtDNA maintenance defects. Our evidence indicates that (1) astrocytes are dependent on mtDNA integrity; (2) mitochondrial metabolism contributes to their activation; (3) chronic astrocyte activation has devastating consequences, underlying spongiotic encephalopathy; and that (4) astrocytes are a potential target for interventions.
2015-10-01 | An approach to epilepsy in mitochondrial disorders of childhood
Mitochondrial epilepsy is commonly seen in certain mtDNA mutations such as mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) and myoclonic epilepsy with ragged red fibres (MERRF) syndromes. They are also seen with mutations in the mtDNA maintenance gene polymerase gamma (POLG) which may manifest with Alpers or Alpers-Huttenlocher syndrome, mitochondrial recessive ataxia syndrome (MIRAS), spinocerebellar ataxia with epilepsy (SCAE), and myoclonus, epilepsy, myopathy, sensory ataxia (MEMSA) syndromes. They are also seen in disorders of Coenzyme Q10 biosynthesis, Complex 1 deficiency and disorders of mitochondrial translation such as with RARS2 gene mutations. The mechanisms for the epileptogenesis may relate to impaired mitochondrial sequestration of calcium, decreased intracellular ATP generation, increased glutamate release into synaptic clefts, increased reactive oxygen species arising from defects in Complex I and Complex III of the respiratory chain, and "stroke-like episodes" as seen in MELAS syndrome. Mitochondrial epilepsy may be characterized by generalized, focal, multifocal or myoclonic seizures in semiology and is critical to control given the further exacerbation of the bioenergetic insufficiency by the heightened energy requirement of seizing neurons. Treatment often consists of a combination of multiple standard anticonvulsants along with vitamins, cofactors, antioxidants and electron donors to enhance mitochondrial function which may be only partially successful. The ketogenic diet is promising but warrants prospective clinical trials. It is important to try to avoid use of mitochondrial toxins such as valproic acid which also exacerbates cellular carnitine deficiency requiring supplementation and which has been associated with rapid neurodegeneration and liver failure in Alpers-Huttenlocher disease.
2012-04-09 | The Ketogenic Diet as a Treatment Paradigm for Diverse Neurological Disorders
Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat – or at least ameliorate symptoms of – these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more “natural” treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.
cell therapies
2026-03-01 | 1399: SUCCESSFUL MANAGEMENT OF ADULT ALPERS-HUTTENLOCHER SYNDROME WITH MANAGEMENT VIA OLT
Introduction: Alpers-Huttenlocher syndrome (AHS) is a rare congenital mitochondrial disease caused by deletions in polymerase gamma (POLG) gene. It typically presents in childhood with seizures and liver failure, but adult-onset cases are exceedingly rare and diagnostically challenging. Liver transplantation has historically been avoided due to concerns over continued neurologic deterioration. We present a critically ill adult with known AHS and acute liver failure managed successfully with orthotopic liver transplantation (OLT) in the ICU. Description: A 21-year-old woman with genetically confirmed AHS due to biallelic pathogenic POLG variants presented to the ICU with new-onset refractory status epilepticus, persistent hypoglycemia, coagulopathy, and acute liver failure. She required vasopressor support and continuous renal replacement therapy for hepatorenal syndrome. Valproate had been recently initiated, and liver biopsy suggested both drug-induced liver injury and underlying disease progression. Her MELD-Na was 31 on admission. Despite her critical state, she was evaluated and approved by a multidisciplinary transplant team. She underwent deceased donor OLT on ICU day three. Her postoperative course was notable for resolution of hepatic dysfunction and resolution of her status epilepticus, although she continued to experience residual seizures and psychomotor symptoms. Discussion: AHS in adults is exceptionally rare, with estimates suggesting fewer than one case per two million individuals. This case highlights the complexity of managing acute liver failure in a critically ill patient with underlying AHS. Valproate can unmask or accelerate hepatic failure in POLG-related disease, typically recognized only once critical decompensation has occurred. While OLT has been considered contraindicated in AHS due to ongoing neurologic decline, this case illustrates that in selected patients, transplant during active multiorgan failure may be lifesaving. Although conclusions cannot be drawn from a single case, this report underscores the need for early recognition, multidisciplinary coordination, and individualized decision-making in the ICU when managing rare mitochondrial syndromes.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Alpers-Huttenlocher syndrome.
1 orphan drug designation for Alpers-Huttenlocher syndrome.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Vatiquinone | small molecules | EMA | PTC Therapeutics International 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.
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.