DeCure for Autosomal recessive distal spinal muscular atrophy 1
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal recessive distal spinal muscular atrophy 1 — 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 moduleAutosomal recessive distal spinal muscular atrophy 1 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 autosomal recessive distal spinal muscular atrophy 1 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
immunoglobulin mu DNA binding protein 2 (IGHMBP2) — IGHMBP2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4B3F · 2.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The 1975 study of chronic proximal spinal muscular atrophy, which predates the identification of the SMN1 gene, examined 38 patients and their families. Among patients with onset before age 2, the incidence of disease in siblings was 1 in 5, consistent with autosomal recessive inheritance. For patients with onset after age 2, the incidence in siblings was 1 in 15, and in their children it was 1 in 8, indicating that both autosomal recessive and dominant forms occurred in that group; the authors concluded that nearly half of patients with onset after 2 had non-genetic motor neuron disease. About a third of patients never walked, and about half were in wheelchairs by age 10.
By 2007, mutations in the telomeric copy of the survival motor neuron gene (SMN1) were known to cause the autosomal recessive form, with disease severity modified by the number of centromeric copies (SMN2). Clinical trials had been performed with three histone deacetylase inhibitors already licensed in the US. Phenylbutyrate showed promise in a mouse model and an open-label pilot study, but was not effective in a phase 2 trial. Valproate induced promising motor-function improvement in patients. Hydroxyurea enhanced splice function and increased the number of nuclear gems in cell studies.
By 2022, 5q spinal muscular atrophy was described as one of the most common paediatric recessive genetic diseases and the most common cause of hereditary infant mortality. Successful therapeutic milestones had been developed, delaying progression and increasing survival. The review noted that SMN-targeted therapies, SMN-independent therapies, and combination therapies were being investigated, with promising data from early-stage clinical trials suggesting additional options might emerge. Another 2022 review confirmed that some treatment drugs had been successfully approved for marketing.
What remains missing is long-term outcome data for the approved and experimental therapies across the full spectrum of disease severity, particularly for patients with later onset or milder forms. The 1975 study’s finding that nearly half of late-onset cases may be non-genetic highlights the need for better patient stratification in trials. Funding for combination therapy trials and for treatments that address non-SMN pathways is still limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 1975 · 52 citations
A CLINICAL AND GENETIC STUDY OF CHRONIC PROXIMAL SPINAL MUSCULAR ATROPHY
AbstractA study of chronic proximal spinal muscular atrophy was undertaken with the main aim of obtaining empirical recurrence risks for genetic counselling. Thirty-eight patients and their families were studied. Of these, 33 had similar clinical features and onset of disease in infancy or childhood. A division of these 33 patients by onset before or after 2 years (which was equivalent to whether or not they ever walked normally) gave recurrence risks for sibs which were higher with early onset. Among the sibs of patients with onset before 2 years, the incidence of disease was 1 in 5, due to most patients having an autosomal recessive disorder. A few patients, however, were thought to represent new dominant mutations. Among the families of index patients with onset after 2 years, the incidence of disease in sibs was only 1 in 15, but among their children it as 1 in 8. Both autosomal recessive and autosomal dominant forms therefore occurred in this age group, but it was concluded that nearly half the patients with onset after 2 had non-genetic motor neuron disease. The autosomal recessive form of chronic spinal muscular atrophy generally had onset before 2 years, but occasionally after 2. About a third of the patients never walked, and about half were in wheelchairs by age 10. No genetic heterogeneity within this form was demonstrated. Three remaining patients had distinctive clinical features associated with their proximal weakness, external ophthalmoplegia in one, dysarthria in another, and joint contractures in a third. Only 2 patients had onset in adult life, one of a probable recessive disorder and the other a probable dominant disorder.
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.
Molecular Pathogenesis and New Therapeutic Dimensions for Spinal Muscular Atrophy
AbstractThe condition known as 5q spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease caused by a deficiency of the ubiquitous protein survival of motor neuron (SMN), which is encoded by the SMN1 and SMN2 genes. It is one of the most common pediatric recessive genetic diseases, and it represents the most common cause of hereditary infant mortality. After decades of intensive basic and clinical research efforts, and improvements in the standard of care, successful therapeutic milestones have been developed, delaying the progression of 5q SMA and increasing patient survival. At the same time, promising data from early-stage clinical trials have indicated that additional therapeutic options are likely to emerge in the near future. Here, we provide updated information on the molecular underpinnings of SMA; we also provide an overview of the rapidly evolving therapeutic landscape for SMA, including SMN-targeted therapies, SMN-independent therapies, and combinational therapies that are likely to be key for the development of treatments that are effective across a patient’s lifespan.
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.
International Journal of Science and Research Archive · 2025 · 0 citations · open access
Combination and sequential treatments for spinal muscular atrophy: First experience with Onasemnogen abeparvovec (Zolgensma®) plus Risdiplam (Everysdi®) in a private hospital in Mexico
AbstractSpinal muscular atrophy is a hereditary neuromuscular disease characterized by the degeneration of alpha motor neurons of the anterior horn of the spinal cord, leading to progressive symmetrical muscle weakness and a high risk for respiratory complications resulting in the need for some degree of ventilatory support. Two infants are presented with hypotonic syndrome in which spinal muscular atrophy was diagnosed by a genetic study. Gene therapy with Zolgensma® with subsequent combination treatment with Risdiplam (Everysdi®) was used to evaluate the clinical improvement in motor function according to the Chop Intend Scale.
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.
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