DeCure for Spinal muscular atrophy-progressive myoclonic epilepsy syndrome
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinal muscular atrophy-progressive myoclonic epilepsy syndrome — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSpinal muscular atrophy-progressive myoclonic epilepsy syndrome maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for spinal muscular atrophy-progressive myoclonic epilepsy syndrome is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
N-acylsphingosine amidohydrolase 1 (ASAH1) — ASAH1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet jrydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6MHM · 2.743 Å · ligand hexylcarbamic acid (JRY). Experimental structure, not a prediction.
What the evidence adds up to
Spinal muscular atrophy with progressive myoclonic epilepsy is a rare syndrome linked to mutations in non-SMN genes, most notably ASAH1. A 2015 report describes a 14-year-old boy with non-5q SMA who later developed severe and drug-resistant myoclonic epilepsy. A 2024 article reports a novel ASAH1 gene mutation, c.118G>C, in a patient presenting with progressive muscle weakness and myoclonic convulsions; electrophysiological investigations confirmed motor neuron disease and generalised epileptic discharge, and a significant time gap was noted between the initial SMA diagnosis and the later appearance of myoclonic seizures. The 2024 authors state that despite therapies aimed at restoring acid ceramidase function, reducing ceramide accumulation, or using gene therapy, the underlying molecular mechanisms remain unknown.
A 1993 article on progressive myoclonus epilepsy notes that there is no cure for patients with this condition. It mentions two drugs available through clinical-research protocols: 5-hydroxy-L-tryptophan and piracetam. The focus of the drug trials described is to control myoclonus and improve quality of life, not to alter the underlying disease. A 2021 report describes a case of SMN gene-unrelated SMA with myoclonic epilepsy supported by electrophysiological and neuropathological evidence, but provides no treatment data.
No controlled trial has tested any drug specifically for the SMA-PME syndrome. The 1993 drug trials were for progressive myoclonus epilepsy generally, not for this ASAH1-linked form. The 2024 authors call for further diagnostic testing and management to determine severity and progression. What is missing is any dedicated clinical trial for this specific syndrome, funding for such trials, and a clear patient stratification strategy given the rarity of the condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Child Neurology · 2002 · 14 citations
Progressive Myoclonic Epilepsies
AbstractThe progressive myoclonic epilepsies are a rare but extremely debilitating group of disorders that are difficult to diagnose and even harder to treat. They represent a heterogeneous subgroup of those with secondary generalized epilepsy. Efficacy of treatment is often measured in terms of slowing a patient's inevitable decline. Reviewed here are the classification of progressive myoclonic epilepsies, features of myoclonic seizures, the five most prevalent progressive myoclonic epilepsy syndromes-Unverricht-Lundborg disease, myoclonus epilepsy with ragged red fibers (MERRF) mitochondrial disease, Lafora's disease, neuronal ceroid lipofuscinoses, and sialidoses-and current treatment options.
Journal of Neurosciences in Rural Practice · 2021 · 5 citations · open access
Spinal Muscular Atrophy and Progressive Myoclonic Epilepsy: A Rare Association
AbstractThe association of spinal muscular atrophy (SMA) with progressive myoclonic epilepsy, also known as "SMA plus," is a unique syndrome linked to non-survival motor neuron (non-SMN) genes. The disease starts in childhood with progressive weakness and atrophy of muscles; myoclonic epilepsy develops during later childhood, after the onset of motor symptoms. In this report, we describe a case of SMN gene unrelated SMA and myoclonic epilepsy, supported by electrophysiological and neuropathological evidences.
The Clinical Challenge pf Progressive Myoclonus Epilepsy
AbstractHealth care providers who care for patients with seizure disorders should be able to recognize progressive myoclonus epilepsy. Progressive myoclonus epilepsy is a syndrome confused with myoclonic seizures and other epilepsies. The main symptom is myoclonus, a brief involuntary muscle jerk of varying intensity that can throw a patient against a wall or to the ground. This article describes major types of progressive myoclonus epilepsy, a typical case presentation and two clinical drug trials available for these patients. The focus of clinical drug trials is to identify a drug that controls the myoclonus and improves the quality of life for the affected individual. There is no cure for patients with progressive myoclonus epilepsy. 5-hydroxy-L-tryptophan and piracetam are two drugs available through clinical-research protocols to patients with progressive myoclonus epilepsy.
ASAH1 Mutation in a Boy with Non-5q SMA and Progressive Myoclonic Epilepsy
AbstractIntroduction: Spinal muscular atrophies (SMA) represent a clinically and genetically heterogeneous group of lower motor neuron diseases, most frequently caused by mutations in the SMN1 gene (5q SMA). Recently, mutations in ASAH1 were found to be responsible for a rare and distinct phenotype of SMA associated with progressive myoclonic epilepsy (PME). Here, we report on the case of a 14-year-old boy with non 5q-SMA who later suffered from severe and drug-resistant myoclonic epilepsy.
Identification of a Novel <i>ASAH1</i> Gene Mutation in Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy.
AbstractSpinal muscular atrophy (SMA) with progressive myoclonic epilepsy (PME) affects the nervous system. Symptoms appear in early childhood and include muscle weakness, difficulty walking, seizures, and cognitive decline. Despite introducing various therapies to restore acid ceramidase function or reduce ceramide accumulation and gene therapy to correct genetic mutations, there are still unknown underlying molecular mechanisms related to this disorder. This article reports a novel variant c.118G>C in the ASAH1 gene. The patient presented with clinical manifestations such as progressive muscle weakness and myoclonic convulsions. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epileptic discharge. A significant temporal interval was observed between the initial diagnosis of SMA and the subsequent manifestation of myoclonic seizures. The proband was genetically assessed through whole exome sequencing (WES) followed by variant confirmation and bioinformatics analysis. According to this article's findings and previous research, further diagnostic testing and management are needed to determine the severity and progression of the patient's condition.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
