DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinal muscular atrophy, type 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 moduleSpinal muscular atrophy, type 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 spinal muscular atrophy, type 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
NLR family apoptosis inhibitory protein (NAIP) — NAIP 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 8FVU · 3.6 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 143 patients with spinal muscular atrophy type 1 born between 1980 and 2006, survival improved significantly for those born in 1995–2006 compared with those born in 1980–1994. The later-born group had a 70% reduction in the risk of death (hazard ratio 0.3, 95% CI 0.2–0.5, p < 0.001) over a mean follow-up of 49.9 months. However, when demographic and clinical care variables were controlled for, year of birth was no longer significantly associated with survival (HR 1.0, 95% CI 0.6–1.8, p = 0.9). Instead, ventilation for more than 16 hours per day, use of a mechanical insufflation-exsufflation device, and gastrostomy tube feeding each showed a significant effect in reducing the risk of death. The survival increase in recent years was attributed to a growing trend toward more proactive clinical care rather than to any specific drug.
More recent reviews describe a dramatic shift in prognosis for SMA type 1 following the introduction of gene therapy and SMN2/SMN1 modifying drugs. Long-term event-free survival and acquisition of important motor milestones are now considered likely for the most severe form of the disease, and prognosis for SMA type 2 has shifted from progressive deterioration to long-term stability. Nevertheless, the same reviews note large heterogeneity in clinical response, ranging from absence of response to impressive improvement. The only factor identified as predictive of treatment success is the age of the patient at initiation of treatment, closely related to disease duration. Many patients still do not benefit from effective treatments or show limited clinical response or impact on quality of life.
One abstract compares the rapidity of therapeutic effect of onasemnogene abeparvovec gene-replacement therapy, as measured by early changes in CHOP-INTEND score, with response to nusinersen in the pivotal phase 3 ENDEAR study, citing a threshold of ≤5-point increase at two months post-dosing. No numerical results from that comparison are given in the abstract. Another review notes that the evidence available for these novel therapies is frequently constrained to a small range of individuals in terms of age and illness stage.
What is still missing is real-world data with standardised outcome markers covering all SMA subtypes, which would be needed to build a platform for clinical decision-making. The evidence for the newer treatments remains limited to narrow age and disease-stage groups. No trial has yet demonstrated efficacy across the full spectrum of SMA type 1 patients, and the heterogeneity of response suggests that patient stratification—by age at treatment, genetic modifiers, or disease duration—has not been adequately addressed. Funding for such broad, long-term observational studies is lacking.
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 · 2007 · 320 citations
The changing natural history of spinal muscular atrophy type 1
AbstractBACKGROUND: Noninvasive ventilation has become increasingly available to spinal muscular atrophy (SMA) patients since the early 1990 s. This is expected to have improved survival for SMA type 1 patients. OBJECTIVE: To assess whether there has been a change in survival in patients with SMA type 1 between 1980 and 2006. METHODS: We used deidentified, family-reported data from participants in the International Spinal Muscular Atrophy Patient Registry and obtained additional clinical information through a mail-in questionnaire. One hundred forty-three patients with SMA type 1 were included in the analysis. Survival of patients born in 1995-2006 (n = 78) was compared with that of patients born in 1980-1994 (n = 65), using the Kaplan-Meier method and Cox proportional hazards models with age at death as the outcome. RESULTS: Patients born in 1995 though 2006 had significantly increased survival compared with those born in 1980-1994 (log-rank test, p < 0.001). In a Cox model, patients born in 1995-2006 had a 70% reduction in the risk of death compared with those born in 1980-1994 (hazard ratio [HR] 0.3, 95% CI 0.2-0.5, p < 0.001) over a mean follow-up of 49.9 months (SD 61.1, median 22.0). However, when controlling for demographic and clinical care variables, year of birth was no longer significantly associated with age at death (HR 1.0, 95% CI 0.6-1.8, p = 0.9), whereas ventilation for more than 16 h/d, use of a mechanical insufflation-exsufflation device, and gastrostomy tube feeding showed a significant effect in reducing the risk of death. CONCLUSION: Survival in spinal muscular atrophy type 1 patients has increased in recent years, in relation to the growing trend toward more proactive clinical care.
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.
Journal of Neuromuscular Diseases · 2018 · 10 citations · open access
Position Statement: Sharing of Clinical Research Data in Spinal Muscular Atrophy to Accelerate Research and Improve Outcomes for Patients
AbstractRecent years have seen increasing clinical research activities in spinal muscular atrophy (SMA), involving patients, their families, clinicians, researchers, regulators and industry This has led to unprecedented advancements in understanding of genetic determinants of severity and prognosis, the natural history, outcome measures, and most importantly first marketed therapies However, many patients with SMA do not benefit yet from effective treatments or show limited clinical response or impact on their quality of life.
Early Diagnosis and Speed to Effect in Spinal Muscular Atrophy Type 1 (SMA1) (S25.002)
AbstractExplore rapidity of therapeutic effect of onasemnogene abeparvovec (AVXS-101) gene-replacement therapy (CL-101 phase 1 study), as measured by early changes in Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score, compared with response to nusinersen in the pivotal phase 3 study (ENDEAR; ≤5-point increase at 2 months postdosing).
Future Journal of Pharmaceuticals and Health Sciences · 2023 · 0 citations · open access
An Overview of Contemporary Phenotypes, Present Challenges, and Novel Implications for Medical Services in the Diagnosis of Spinal Muscular Atrophy
AbstractSpinal muscular atrophy (SMA) is a form of muscle disease induced by SMN1 gene mutations. It can cause motor neurons and muscle strength to weaken. The intensity of the disease’s progression varies depending on the stage of development. Over the past ten years, new ways to help people with SMA have been found. These include the use of gene therapy and the modification of the SMN2 and SMN1 genes. First drugs approved for this condition were able to significantly alter the course of the disease. However, the evidence that is now available for these novel therapies is frequently constrained to a small range of individuals in terms of age and illness stage. To better unde rstand the impact of treatment on people with all SMA subtypes and to build a platform for clinical decision - making in SMA, it will be necessary to gather real - world data with standardized outcome markers.
FV 953. Parents’ Experiences during the Compassionate Use Program (Nusinersen) for Patients with Spinal Muscular Atrophy Type 1—A Qualitative Interview Study
AbstractBackground: Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by a progressive proximal muscular weakness. Children diagnosed with SMA Type 1 rarely live longer than 1 to 4 years. Since May 30, 2017, Nusinersen has been approved by the European Medicines Agency. Before the official approval, patients with SMA Type 1 had the opportunity to access treatment with Nusinersen within a Compassionate Use Program (CUP). Thus, effective treatment was within reach for the very first time.
Arquivos de Neuro-Psiquiatria · 2023 · 0 citations · open access
Intrathecal administration of Nusinersen in children and adolescent SMA type 1 and 2
AbstractBackground: Spinal muscular atrophy (SMA) is an autosomal-recessive disorder resulting in progressive muscle weakness. In August 2017, the Agência Nacional de Vigilância Sanitária (ANVISA) approved the first treatment for SMA, a drug named nusinersen that is administered intrathecally. However, many patients with SMA have neuromuscular scoliosis or spinal instrumentation resulting in challenging intrathecal access. Many centers use radiological methods to guide lumbar puncture, such as ultrasound, videofluoroscopy or tomography, but these methods are often available only in referral centers.
Clinical Practice Guideline for Adolescent and Adult Patients with Spinal Muscular Atrophy – Part 1
AbstractIn recent years, the field of spinal muscular atrophy (SMA) has made progress in multidisciplinary care and disease-modifying therapies (DMTs). 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.
