DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinal muscular atrophy, type IV — 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, type IV 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, type iv 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
methylcrotonyl-CoA carboxylase subunit 2 (MCCC2) — MCCC2 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 btndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8XL6 · 2.29 Å · ligand BIOTIN (BTN). Experimental structure, not a prediction.
What the evidence adds up to
Three drugs are approved for spinal muscular atrophy: nusinersen, onasemnogene abeparvovec, and risdiplam. All three improved motor milestones in patients compared to the natural history of the disease, according to a systematic review of 40 publications. The same review found that hydroxyurea and valproic acid showed slight improvement, while gabapentin and phenylbutyrate had no effect. These drugs were authorised through accelerated programmes, and post-marketing studies were required as a condition of approval. As of January 2023, 69 post-marketing studies had been registered, primarily aimed at assessing risk-benefit profiles in populations not included in pivotal trials and investigating long-term safety and clinical benefit.
Drug repurposing for SMA has been explored with branaplam, riluzole, olesoxime, harmine, and prednisolone, but the review from 2024 states that the current repurposing strategy lacks systematicity and depends more on serendipitous discoveries than organised approaches. A 2019 mini-review noted that not all SMA patients will gain maximal benefit from approved SMN genetic therapies due to limited accessibility, high costs, and differential effects depending on timing of administration and disease severity. The RESTORE registry was established to integrate real-world data across single-product registries and overcome limitations in data collection and cross-registry patient continuity.
No abstract specifically addresses type IV SMA. The approved drugs and repurposed candidates are discussed for SMA generally, without stratification by subtype. The 2024 systematic review reports that hydroxyurea and valproic acid showed only slight improvement, and gabapentin and phenylbutyrate had no effect. What remains missing is systematic, mechanism-driven repurposing trials that target the molecular origins of SMA, adequate funding for such trials, and patient stratification by disease type and severity to determine whether any repurposed drug offers meaningful benefit for type IV patients specifically.
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 Sciences · 2023 · 19 citations · open access
Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical–Experimental, and Real-World Evidence
AbstractSpinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. The preclinical evidence on the drugs approved for SMA allowed a significant acceleration in the experimental phase of these drugs. However, since these drugs had been authorized through accelerated programs, the conduction of post-marketing studies was requested as a condition of their marketing approval to better understand their risk-benefit profiles in real-world settings. As of the 4 January 2023, a total of 69 post-marketing studies concerning the three orphan drugs approved for SMA were identified in clinicaltrials.gov (N = 65; 94.2%) and in the EU PAS register (N = 4; 5.8%). Currently, ongoing studies are primarily aimed at providing evidence concerning the risk-benefit profile of the three drugs in specific populations that were not included in the pivotal trials and to investigate the long-term safety and clinical benefits of these drugs. Real-world data sources collecting information regarding the natural history of the disease and post-marketing surveillance of the available therapies are increasingly becoming essential for generating real-world evidence on this rare disease and its orphan drugs.
Future Neurology · 2019 · 9 citations · open access
Teaching An Old Drug New Tricks: Repositioning Strategies for Spinal Muscular atrophy
AbstractSpinal muscular atrophy (SMA) is a childhood disorder caused by loss of the SMN gene. Pathological hallmarks are spinal cord motor neuron death, neuromuscular junction dysfunction and muscle atrophy. The first SMN genetic therapy was recently approved and other SMN-dependent treatments are not far behind. However, not all SMA patients will reap their maximal benefit due to limited accessibility, high costs and differential effects depending on timing of administration and disease severity. The repurposing of commercially available drugs is an interesting strategy to ensure more rapid and less expensive access to new treatments. In this mini-review, we will discuss the potential and relevance of repositioning drugs currently used for neurodegenerative, neuromuscular and muscle disorders for SMA.
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.
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).
Annals of the Academy of Medicine Singapore · 2024 · 1 citations · open access
A consensus survey of neurologists and clinical geneticists on spinal muscular atrophy treatment in Singapore
AbstractJust a decade ago, spinal muscular atrophy (SMA) was considered a debilitating, progressive neuromuscular disease that inevitably led to chronic disability and a shortened lifespan. Now, it is treatable with nusinersen, onasemnogene abeparvovec (OAV) and risdiplam—the 3 disease-modifying drugs approved by the US Food and Drug Administration, the European Medicines Agency and most recently, the Health Science Authority in Singapore.1 Clinical trials and real-world data have consistently shown improvement in motor milestones for all 3 drugs, especially if introduced early in the disease course.2-4 More significantly, presymptomatic treatment has enabled age-appropriate development of motor milestones, leading to improved respiratory, orthopaedic and nutritional outcomes.
Archives of Community Medicine and Public Health · 2021 · 0 citations · open access
Spinal Muscular Atrophy - The disease and its treatments
AbstractLess than a decade ago, patients diagnosed with Spinal Muscular Atrophy (SMA) had no treatments other than pulmonary, gastrointestinal, and orthopedic care. These palliative treatments were focused on managing symptoms and did not address the cause of the disease itself. Now, there are several FDA (U.S. Food and Drug Administration) approved drugs to treat SMA, which can stop or slow disease progression. In order to discuss the development of treatments for patients with SMA, the disease must first be explained in detail.
International Journal of Pharmaceutical Sciences and Drug Research · 2024 · 0 citations · open access
Spinal Muscular Atrophy: A Systematic Review of Diagnosis, Treatment and Emerging Research
AbstractThis systematic review aims at understanding the causes, consequences and therapy of spinal muscular atrophy, which is an inheritable illness which can be fatal at times. Although spinal muscular atrophy is incurable, various drugs have been developed to ameliorate the disease condition and this article aims at understanding the effect of all the available synthetic drugs on Spinal muscular atrophy (SMA). A search plan was curated using various databases like, PubMed, Google Scholar and Science Direct. Authors selected publications of Risdiplam, Onasemnogene abeparvovec and Nusinersen, and even studies comparing the drugs with one another, including studies related to drugs like hydroxyurea, phenylbutyrate and gabapentin. 40 publications were identified and finalized based on preferences. All the 3 approved drugs improved motor milestones in SMA patients as compared to natural cohort of the disease. Although Gene replacement therapy observed tremendous results, further investigations is needed to be done. Other drugs like hydroxyurea (HU), Gabapentin, Valproic acid and phenylbutyrate showed significant, little and no effect respectively. All 3 drugs showed significant outcomes and were safe and effective in the longer duration of use. Hydroxyurea and Valproic acid showed slight improvement whereas Gabapentin and Phenylbutyrate had no effect.
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.
