DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for amyotrophic lateral sclerosis type 5 — 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 moduleAmyotrophic lateral sclerosis type 5 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 amyotrophic lateral sclerosis type 5 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
SPG11 vesicle trafficking associated, spatacsin (SPG11) — SPG11 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 8YAH · 3.3 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Amyotrophic lateral sclerosis is a fatal motor neuron progressive disorder for which no treatment exists to date. Riluzole, a drug that has only modest benefit in extending survival, is still the only medication approved by the FDA for the treatment of ALS. Edaravone was recently approved in Japan and is pending in the USA. Despite multiple obstacles that explain the absence of effective drugs, joint efforts among patient's associations, public and private sectors have resulted in several compounds that are in the late stages of clinical trials. Drug repositioning is playing an important role, having achieved the approval of some orphan drug applications in late phases of clinical development.
Numerous theories of cause and pathogenesis have been advanced but specific mechanisms have not yet been established. The disease 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 involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors. Recent progress has revealed a number of molecular and cellular processes that can potentially be used as therapeutic targets, and a repertoire of drugs able to restore, at least partially, their functionality has been developed for other diseases.
Based on the available data, combination drug therapies should be considered for future clinical trials. The journey to understanding or treating amyotrophic lateral sclerosis is still a long one. Studying the emergence of new therapies may help to further understanding of the pathogenic mechanisms of the disease.
What is still missing is a clear understanding of the causative factors in ALS, which prevents rational targeting of therapies. The disease's heterogeneity means that patient stratification is not yet possible, and no trial design has been able to demonstrate a drug that slows, arrests, or reverses disease progression beyond riluzole's modest survival extension. Adequate funding for late-stage trials of repurposed drugs remains a barrier.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2005 · 62 citations
Amyotrophic lateral sclerosis: recent advances and future therapies
AbstractPURPOSE OF REVIEW: Amyotrophic lateral sclerosis is a rare but fatal motoneuron disorder. Despite intensive research riluzole remains the only available therapy, with only marginal effects on survival. Here we review some of the recent advances in the search for a disease-modifying therapy for amyotrophic lateral sclerosis. RECENT FINDINGS: A number of established agents have recently been re-investigated for their potential as neuroprotective agents, including beta-lactam antibiotics and minocycline. Progress has also been made in exploiting growth factors for the treatment of amyotrophic lateral sclerosis, partly due to advances in developing effective delivery systems to the central nervous system. A number of new therapies have also been identified, including a novel class of compounds, heat-shock protein co-inducers, which upregulate cell stress responses thereby mediating neuroprotection. Non-drug-based therapies are also under development, with progress in gene-silencing and stem cell therapies. SUMMARY: In the past few years, significant advances have been made in both our understanding of amyotrophic lateral sclerosis pathogenesis and the development of new therapeutic approaches. However, caution must be exercised in view of the long-standing failure to successfully transfer therapeutic compounds to the clinic. A deeper awareness in the research community of the need for clinically relevant preclinical studies, coupled with a better understanding of the issues surrounding clinical trial design for amyotrophic lateral sclerosis, offers hope that the growing list of validated preclinical therapeutics can finally yield an effective disease-modifying treatment.
Encyclopedia of Life Sciences · 2001 · 51 citations
Amyotrophic Lateral Sclerosis
AbstractAbstract Amyotrophic lateral sclerosis is a heterogeneous neurodegenerative syndrome that has been described in the medical literature for 150 years. Numerous theories of cause and pathogenesis have been advanced but specific mechanisms have not yet been established. What is highly likely is that numerous injurious agents can precipitate the cascade of events that results in this well‐known syndrome. In the absence of knowing specific cause(s), understanding this pathogenetic mechanism may be a target for novel drug discovery efforts.
Expert Opinion on Investigational Drugs · 2017 · 33 citations
Drugs in clinical development for the treatment of amyotrophic lateral sclerosis
AbstractINTRODUCTION: Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron progressive disorder for which no treatment exists to date. However, there are other investigational drugs and therapies currently under clinical development may offer hope in the near future. Areas covered: We have reviewed all the ALS ongoing clinical trials (until November 2016) and collected in Clinicaltrials.gov or EudraCT. We have described them in a comprehensive way and have grouped them in the following sections: biomarkers, biological therapies, cell therapy, drug repurposing and new drugs. Expert opinion: Despite multiple obstacles that explain the absence of effective drugs for the treatment of ALS, joint efforts among patient's associations, public and private sectors have fueled innovative research in this field, resulting in several compounds that are in the late stages of clinical trials. Drug repositioning is also playing an important role, having achieved the approval of some orphan drug applications, in late phases of clinical development. Endaravone has been recently approved in Japan and is pending in USA.
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.
Expert Opinion on Pharmacotherapy · 2004 · 23 citations
Current pharmacological management of amyotropic lateral sclerosis and a role for rational polypharmacy
AbstractAmyotrophic [corrected] lateral sclerosis (ALS) is a progressive degenerative condition of motor neurons that is ultimately fatal. Even though scientific discovery over the past few decades has led to a greater understanding of the pathogenic mechanisms of ALS, effective pharmacotherapy intended to slow, arrest or reverse the disease progression remains difficult to obtain. Riluzole, a drug that has only modest benefit in extending survival, is still the only medication approved by the FDA for the treatment of ALS. However, a number of pharmacological agents are currently being investigated as potential therapy for ALS. This paper will review the pathophysiology of ALS and current pharmacological management of the disease and recent directions in research and clinical trials. Based on the available data, it is our opinion that combination drug therapies should be considered for future clinical trials.
In a search for efficient treatment for amyotrophic lateral sclerosis: Old drugs for new approaches
AbstractRecent progress in understanding the pathological changes in the nervous system and in certain other body systems (e.g., immune system) that lead to the development and progression of amyotrophic lateral sclerosis (ALS) revealed a number of molecular and cellular processes that can potentially be used as therapeutic targets. Many of these processes are compromised not only in ALS but also in other diseases and a repertoire of drugs able to restore, at least partially, their functionality has been developed. In this review, we briefly describe current approaches to the repurposing of such "old" drugs for treatment of patients with ALS.
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.
