DeCure for X-linked distal spinal muscular atrophy type 3
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for X-linked distal spinal muscular atrophy type 3 — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleX-linked distal spinal muscular atrophy type 3 maps to a 3-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 x-linked distal spinal muscular atrophy type 3 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
phosphoglycerate kinase 1 (PGK1) — PGK1 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9FDF · 1.44 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
Ten patients with spinal muscular atrophy IIIb were followed for at least ten years. Muscle strength declined in all muscles examined, usually by no more than one MRC grade every five years, with some muscles appearing stationary for five to ten year periods. Weakness appeared first in triceps, then biceps and deltoid in the upper limbs, and first in thigh adductors, then iliopsoas, quadriceps femoris, hamstrings, thigh abductors, and gluteus maximus in the lower limbs. The pattern was remarkably uniform between patients.
A 2024 review of repurposed drugs for spinal muscular atrophy lists branaplam, riluzole, olesoxime, harmine, and prednisolone as having shown some improvement in treating SMA. The same review states that the repurposing strategy currently lacks systematicity and depends more on serendipitous discoveries than organised approaches. A 2025 clinical practice guideline for adolescent and adult SMA patients in China notes that survival and quality of life have improved with multidisciplinary care and disease-modifying therapies, but provides no data specific to distal spinal muscular atrophy type 3.
Onasemnogene abeparvovec, a gene replacement therapy for 5q SMA, is described as strikingly effective but is approved only for children under two years of age. No abstract addresses X-linked distal spinal muscular atrophy type 3 directly. What is missing for this specific form is any dedicated clinical trial, any natural history data beyond the SMA IIIb cohort, any repurposing study targeting the X-linked mechanism, and any funding or patient stratification strategy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2008 · 65 citations
Natural history of SMA IIIb
AbstractOBJECTIVE: To assess the natural progression of muscle weakness in spinal muscular atrophy (SMA) IIIb. METHODS: Ten patients with SMA IIIb were followed for at least 10 years. Age at disease onset varied between 9 and 18 years. Patients were initially seen 2 to 10 years after disease onset. They were evaluated at approximately 2, 5, 10, 15, and 20 years of disease duration depending on the timing of their initial visit after onset. Medical Research Council (MRC) scale was used with particular attention to proximal muscles. RESULTS: The MRC grade declined with years in all of the muscles. The decline was usually not more than by one MRC grade for each 5-year period. There were 5-10 year periods when some muscles appeared to remain stationary. The succession of weakness was first triceps, then biceps and deltoid for upper extremity muscles and first thigh adductors, then iliopsoas, then quadriceps femoris, then hamstrings, thigh abductors, and gluteus maximus for lower extremity muscles. There was a remarkable uniformity between patients in the MRC grade for each muscle at each stage: in the first 5 years of the disease, triceps, iliopsoas, thigh adductors, and quadriceps femoris were the muscles which had noticeable weakness. CONCLUSIONS: These findings show that strength in spinal muscular atrophy IIIb decreases over time, explaining the progressive functional loss. The sequence of weakness in the lower extremities suggests that the disease starts segmentally involving the upper lumbar segments of the medulla spinalis initially. The slowness of the deterioration may have implications for clinical trials.
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.
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.
Expert Opinion on Orphan Drugs · 2021 · 0 citations
An evaluation of onasemnogene abeparvovec for spinal muscular atrophy (<i>SMN1</i>)
AbstractIntroduction Onasemnogene abeparvovec is the first systemic gene replacement therapy approved by the FDA for any inherited condition and is the second FDA-approved genetic therapy for 5q spinal muscular atrophy.Areas covered We discuss the design and preclinical development of onasemnogene abeparvovec, along with clinical trial and real-world data focusing on efficacy and safety.Expert Opinion Although onasemnogene abeparvovec is strikingly effective for the treatment of 5q SMA, it is only approved for use under the age of 2 years and there are also two other FDA-approved molecular-based treatments. Many questions remain in terms of treatment selection, possibility of dose optimization, and combinational therapies.
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.
