DeCure for Spinal muscular atrophy, distal, autosomal recessive, 6
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinal muscular atrophy, distal, autosomal recessive, 6 — 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, distal, autosomal recessive, 6 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, distal, autosomal recessive, 6 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.
What the evidence adds up to
Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by mutations in the SMN1 gene, with disease severity modified by the number of SMN2 copies and the quantity of survival motor neuron protein. Histone deacetylase inhibitors have been tested because they appear to increase SMN2 expression and SMN protein in various cell types. Phenylbutyrate showed promise in a mouse model and an open-label pilot study, but was not effective in a phase 2 trial. Valproate may enhance transcription and reverse SMN2 splicing pattern, and has induced promising motor-function improvement in patients. Hydroxyurea may enhance splice function and increase the number of nuclear gems where SMN protein concentrates.
A 2024 review lists repurposed drugs that have shown some improvement in treating SMA, including branaplam, riluzole, olesoxime, harmine, and prednisolone. The same review states that effective treatments or interventions remain elusive despite comprehensive investigations, and that the current strategy for medication repurposing lacks systematicity and frequently depends more on serendipitous discoveries than on organised approaches. The RESTORE registry was established to integrate real-world data on SMA patients and overcome limitations of existing single-product registries, but no results from that registry are reported in the provided abstracts.
Two 2025 clinical practice guidelines from China note that survival and quality of life have significantly improved with multidisciplinary care and disease-modifying therapies, but state that no clinical practice guidelines previously existed for adult and adolescent SMA patients. A 2022 review covering 100 years of SMA history describes the progression from clinical description to gene cloning, animal models, and novel therapies, but identifies the future as lying in breakthroughs in pathophysiological mechanism, carrier screening, and new therapies.
What is still missing is a systematic, mechanism-targeted approach to drug repurposing rather than reliance on serendipity. No large randomised controlled trial data are reported for any of the repurposed drugs mentioned. Patient stratification by SMN2 copy number or other biomarkers is not addressed in the repurposing studies. Funding for systematic screening and for trials that can confirm or refute the preliminary signals from valproate, hydroxyurea, and the other repurposed candidates remains absent from the evidence provided.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Pediatrics · 2007 · 35 citations
Clinical trials in spinal muscular atrophy
AbstractPURPOSE OF REVIEW: Spinal muscular atrophy is a neuromuscular disorder manifesting as weakness and hypotonia across a broad spectrum of severity. Mutations in the telomeric copy of the survival motor neuron gene (SMN1) cause the autosomal recessive form. Disease severity is modified by the number of centromeric copies of the gene (SMN2) and the quantity of survival motor neuron protein. This has given rise to a number of treatment strategies. RECENT FINDINGS: Histone deacetylase inhibitors appear to increase the expression of SMN2, with an increase in survival motor neuron protein in various cell types. Clinical trials have been performed with three histone deacetylase inhibitors which are already licensed in the USA. Phenylbutyrate showed promise in a mouse model and an open-label pilot study, but was not effective in a phase 2 trial. Valproate may enhance transcription and reverse SMN2 splicing pattern, and has induced promising motor-function improvement in patients. Hydroxyurea may enhance splice function and increase the number of nuclear 'gems', small nuclear organelles in which survival motor neuron protein concentrates. SUMMARY: Discoveries regarding the genetics and pathogenesis of spinal muscular atrophy have identified potential targets for pharmacotherapy, raising hope that better treatments will eventually be developed.
Revista médica de Chile · 2011 · 11 citations · open access
Atrofia muscular espinal: Caracterización clínica, electrofisiológica y molecular de 26 pacientes
AbstractBACKGROUND: Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder affecting the anterior horn cells of the spinal cord resulting in muscle weakness and atrophy, linked to the homozygous disruption of the survival motor neuron 1 (SMN1) gene. It is the leading genetic cause of infant death. It has been classified into three types based on the severity of symptoms. Type I SMA is the most severe form with death within the first 2 years of life. Type II and III SMA patients show intermediate and mild forms of the disorder. AIM: To describe the clinical and electrophysiological findings of 26 Chilean patients with SMA with molecular confirmation. PATIENTS AND METHODS: Retrospective multicenter analysis of patients with SMA assessed between 2003 and 2010. The diagnosis was suspected on clinical and electrophysiological criteria. Since 2006 molecular genetics confirmation was implemented in one of our centers. RESULTS: Twenty-six patients between 2 months and 18 years of age at presentation were analyzed; 15 (58%) were males. SMA I, II and III clinical criteria were observed in 4 (15.4 %), 11 (42.3%) and 11 (42.3%)patients, respectively. All had proximal muscle weakness and atrophy. Electromyography showed features of acute denervation or re-innervation with normal motor and sensory nerve conduction. Nine patients required a muscle biopsy. The genetic confirmation of the disease by PCR technique followed by restriction fragment length polymorphism method disclosed the SMN1 gene deletion in all 26 cases. All patients died secondary to respiratory failure, between eight and 14 months of life. CONCLUSIONS: An adequate clinical and molecular diagnosis of spinal muscular atrophy will help for a better management of these patients.
Cellular and Molecular Neurobiology · 2024 · 5 citations · open access
Spinal Muscular Atrophy: Current Medications and Re-purposed Drugs
AbstractSpinal muscular atrophy (SMA) is an autosomal recessive genetic neuromuscular disorder that is characterized by gradual muscle weakness and atrophy due to the degeneration of alpha motor neurons that are present on the anterior horn of the spinal cord. Despite the comprehensive investigations conducted by global scientists, effective treatments or interventions remain elusive. The time- and resource-intensive nature of the initial stages of drug research underscores the need for alternate strategies like drug repurposing. This review explores the repurposed drugs that have shown some improvement in treating SMA, including branaplam, riluzole, olesoxime, harmine, and prednisolone. The current strategy for medication repurposing, however, lacks systematicity and frequently depends more on serendipitous discoveries than on organized approaches. To speed up the development of successful therapeutic interventions, it is apparent that a methodical approach targeting the molecular origins of SMA is strictly required.
Recent research on the treatment of spinal muscular atrophy.
AbstractSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscular weakness and atrophy. SMA, as an inherited disease, is the leading cause of death in infants and young children. Rapid progress has been made in the research field of SMA in recent years, and some related treatment drugs have been successfully approved for marketing. This article reviews the recent research advances in the treatment of SMA.
Real-World Treatment Patterns and Outcomes in Patients with Spinal Muscular Atrophy Collected from the RESTORE Registry (2470)
AbstractTo integrate and significantly expand available real-world data on patients with spinal muscular atrophy (SMA) by establishing RESTORE – a comprehensive registry of patients with SMA specifically designed to overcome the recognized limitations of existing single-product registries (eg, dissimilarities in data collection, lack of cross-registry patient continuity, and limited access by researchers).
Clinical Practice Guideline for Adolescent and Adult Patients with Spinal Muscular Atrophy – Part 3
AbstractIn recent years, the field of spinal muscular atrophy (SMA) has made progress in multidisciplinary care and disease-modifying therapies. Survival and the quality of life of patients have significantly improved. However, no clinical practice guidelines exist for the management of SMA in adult and adolescent patients. Multidisciplinary experts from a number of tertiary medical centers in China, specializing in the diagnosis and treatment of SMA, came together to remedy this using evidence-based medicine. This guideline serves as an instrumental reference for the standardized care of Chinese SMA patients.
Clinical Practice Guideline for Adolescent and Adult Patients with Spinal Muscular Atrophy – Part 2
AbstractIn recent years, the field of spinal muscular atrophy (SMA) has made progress in multidisciplinary care and disease-modifying therapies. Survival and the quality of life of patients have significantly improved. However, no clinical practice guidelines exist for the management of SMA in adult and adolescent patients. Multidisciplinary experts from a number of tertiary medical centers in China, specializing in the diagnosis and treatment of SMA, came together to remedy this using evidence-based medicine. This guideline serves as an instrumental reference for the standardized care of Chinese SMA patients.
DOAJ (DOAJ: Directory of Open Access Journals) · 2022 · 0 citations
Spinal Muscular Atrophy: History, Current Status and Future
AbstractIt has been a hundred years since the first case of spinal muscular atrophy(SMA) was reported in the medical literature. In its 100 years of history, medical development for the cure of SMA has gone through many stages, from clinical manifestation description, accumulation of cases, disease classification exploration to pathogenic gene mapping and cloning, clinical application of gene diagnosis, animal model establishment then to R&D of disease modifying drugs and clinical use of novel therapies. The future of the development lies in breakthrough in pathophysiological mechanism, carrier screening and precise prevention, as well as new therapies. As a representative of monogenic rare diseases, review the history of the progress in diagnosis and treatment and R&D in medications and discuss the prospect of further development in the future is instrumental in leading the continued advancement of the whole cause of rare disease.
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.
