DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for sporadic amyotrophic lateral sclerosis — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSporadic amyotrophic lateral sclerosis maps to a 14-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 sporadic amyotrophic lateral sclerosis 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
superoxide dismutase 1 (SOD1) — SOD1 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 udidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8CCX · 1.665 Å · ligand butane-1,4-dithiol (UDI). Experimental structure, not a prediction.
What the evidence adds up to
The 2017 review notes that sequencing technologies have expanded the number of genes associated with amyotrophic lateral sclerosis, including rare but highly penetrant causative mutations and common risk alleles. These discoveries implicate diverse biological pathways essential for motor neuron health and suggest ALS pathogenesis is a heterogeneous, multistep process. The review states that insights from these gene discoveries are leading to a new generation of targeted therapies directed at specific genes.
The 2023 review states that the cause of ALS remains unexplained despite years of research, and that the disease is likely due to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways. It says the progression involves multiple cellular processes and that the interaction between different complex mechanisms makes it difficult to identify causative factors. The review discusses currently proposed potential mechanisms and their evidence, as well as emerging treatment strategies, but offers no concrete survival or response data from any trial.
The 2005 review of clinical trials in ALS states that the past decade of research contributed to a greater understanding of the disease process, the development of relevant animal models, and the identification of several therapeutic approaches that may delay disease progression. It presents completed and ongoing clinical trials and the process of selecting drugs for trials, but provides no numerical outcomes such as survival rates or response rates from any specific trial.
What is still missing is a clear, single causative mechanism that can be targeted across the patient population. No abstract reports a successful phase 3 trial with a survival benefit. The field lacks validated biomarkers for patient stratification, and the heterogeneity of the disease means that even targeted therapies may only apply to small genetic subgroups. Adequate funding for large, stratified trials and for basic research into the complex interplay of pathways remains insufficient.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Oxford University Press eBooks · 2017 · 29 citations
Amyotrophic Lateral Sclerosis
AbstractRecent advances in sequencing technologies have dramatically expanded the number of genes associated with amyotrophic lateral sclerosis, including rare but highly penetrant causative mutations as well as common risk alleles. This chapter discusses these gene discoveries and how they have implicated a diverse array of biological pathways essential for motor neuron health and have begun to inform our understanding of ALS pathogenesis as a heterogeneous and multistep process. Insights from these discoveries are leading to a new generation of targeted therapies directed at specific genes and are poised to inform how patients with amyotrophic lateral sclerosis are evaluated and treated in the clinic.
Neural Regeneration Research · 2023 · 28 citations · open access
Pathological mechanisms of amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system, the cause of which remains unexplained despite several years of research. Thus, the journey to understanding or treating amyotrophic lateral sclerosis is still a long one. According to current research, amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic pathways. The progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral sclerosis. Here, we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis, as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral sclerosis. In addition, we discuss current emerging strategies for the treatment of amyotrophic lateral sclerosis. Studying the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.
The Journal of Clinical Pharmacology · 2005 · 15 citations
Clinical Trials in Amyotrophic Lateral Sclerosis: The Tenuous Past and the Promising Future
AbstractThe past decade of research in amyotrophic lateral sclerosis has contributed to a greater understanding of the disease process, the development of relevant animal models, and the identification of several therapeutic approaches that may delay disease progression. Completed and ongoing clinical trials and the process of selecting drugs for clinical trials are presented.
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.
