DeCure for Scapuloperoneal spinal muscular atrophy
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Scapuloperoneal spinal muscular atrophy — 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 moduleScapuloperoneal spinal muscular atrophy 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 scapuloperoneal spinal muscular atrophy 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
transient receptor potential cation channel subfamily V member 4 (TRPV4) — TRPV4 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 2~{r}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8T1E · 2.77 Å · ligand [(2~{R})-2-[(~{Z})-hexadec-9-enoyl]oxy-3-[oxidanyl-[2-(trimethyl-$l^{4}-azanyl)ethoxy]phosphoryl]oxy-propyl] (~{Z})-docos-13-enoate (9ZR). Experimental structure, not a prediction.
What the evidence adds up to
Spinal muscular atrophy is an autosomal recessive neuromuscular disorder caused by loss of the SMN1 gene, with disease severity modified by SMN2 copy number and survival motor neuron protein quantity. SMA type 1, the most severe form with earliest onset, has shifted from a rapidly lethal disease to one where long-term event-free survival and acquisition of motor milestones are now likely, and SMA type 2 prognosis has shifted from progressive deterioration to long-term stability. However, clinical response to currently available treatments shows large heterogeneity, ranging from absence of response to impressive improvement, and the only identified predictor of treatment success is the patient's age at treatment initiation, closely related to disease duration.
Histone deacetylase inhibitors have been tested in clinical trials for SMA. 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 induced promising motor-function improvement in patients. Hydroxyurea may enhance splice function and increase the number of nuclear gems where survival motor neuron protein concentrates. A 2024 review lists branaplam, riluzole, olesoxime, harmine, and prednisolone as repurposed drugs that have shown some improvement in treating SMA, but notes that effective treatments or interventions remain elusive overall.
The first SMN genetic therapy was recently approved and other SMN-dependent treatments are not far behind, but not all SMA patients will reap maximal benefit due to limited accessibility, high costs, and differential effects depending on timing of administration and disease severity. Repurposing commercially available drugs is proposed as a strategy for more rapid and less expensive access to new treatments, but the current repurposing approach lacks systematicity and frequently depends more on serendipitous discoveries than on organised methods. What is still missing is a methodical approach targeting the molecular origins of SMA, as well as systematic trial designs and patient stratification that could account for the wide heterogeneity in clinical response.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Therapeutics and Clinical Risk Management · 2019 · 200 citations · open access
<p>Clinical Evidence Supporting Early Treatment Of Patients With Spinal Muscular Atrophy: Current Perspectives</p>
AbstractRecent advances in the treatment of spinal muscular atrophy (SMA) have dramatically altered prognosis. Rather than a rapidly lethal disease, SMA type 1, the most severe form with the earliest onset of SMA, has become a disease in which long-term event-free survival with the acquisition of important motor milestones is likely. Prognosis for patients with SMA type 2 has shifted from slow and progressive deterioration to long-term stability. Nevertheless, there is a large heterogeneity in terms of clinical response to currently available treatments, ranging from absence of response to impressive improvement. The only factor identified that is predictive of treatment success is the age of the patient at the initiation of treatment, which is closely related to disease duration. The aim of this paper is to review available evidence that support early intervention using currently available treatment approaches.
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.
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.
The Biochemistry of Survival Motor Neuron Protein Is Paving the Way to Novel Therapies for Spinal Muscle Atrophy
AbstractSpinal muscle atrophy (SMA) is the leading genetic cause of infant mortality. SMA originates from the loss of functional survival motor neuron (SMN) protein. In most SMA cases, the SMN1 gene is deleted. However, in some cases, SMN is mutated, impairing its biological functions. SMN mutants could provide clues about the biological functions of SMN and the specific impact on SMA, potentially leading to the identification of new pathways and thus providing novel treatment alternatives, and even personalized care. Here, we discuss the biochemistry of SMN and the most recent SMA treatment strategies.
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 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.
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.
