DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for amyotrophic lateral sclerosis 28 — 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 28 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 28 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.
What the evidence adds up to
Riluzole remains the only approved therapy for amyotrophic lateral sclerosis, and its effect on survival is only marginal. A 2007 review notes that no other effective therapies had emerged in the ten years after riluzole’s approval. A 2005 review states that a number of established agents, including beta-lactam antibiotics and minocycline, had been re-investigated as potential neuroprotective agents, but it does not report positive results from those investigations. The same review also mentions progress in exploiting growth factors, partly due to advances in delivery systems to the central nervous system, and the identification of heat-shock protein co-inducers as a novel class of compounds that upregulate cell stress responses.
A 2001 review states that specific mechanisms of ALS pathogenesis had not yet been established, and that numerous injurious agents could precipitate the syndrome. A 2020 review notes that recent progress in understanding pathological changes in the nervous system and immune system has revealed molecular and cellular processes that could serve as therapeutic targets, and that a repertoire of drugs developed for other diseases is being investigated for repurposing in ALS. The 2005 review on clinical trials presents completed and ongoing trials and the process of selecting drugs, but does not report any positive efficacy data from those trials.
The 2005 review on recent advances explicitly cautions that there has been a long-standing failure to successfully transfer therapeutic compounds to the clinic. It calls for clinically relevant preclinical studies and a better understanding of clinical trial design for ALS. The 2007 review emphasises the need for scientific evidence supporting the selection of each drug being tested, as well as attention to trial design. What is still missing is a validated preclinical therapeutic that has successfully translated into an effective disease-modifying treatment in the clinic, along with trial designs that can reliably detect such an effect and patient stratification to account for the heterogeneity of the syndrome.
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 · 2007 · 33 citations
Current clinical trials in amyotrophic lateral sclerosis
AbstractAmyotrophic lateral sclerosis is caused by selective degeneration of motor neurons in the brain and spinal cord. There are still no other effective therapies 10 years after the approval of riluzole for the treatment of amyotrophic lateral sclerosis, but advances in drug development and screening are substantially increasing the number of potential therapeutic agents. This review provides an overview of clinical trial methodology in amyotrophic lateral sclerosis followed by a systematic evaluation of drugs that are presently in Phase I, II and III clinical trials. There is an emphasis on the scientific evidence supporting the selection of each drug being tested, as well as on trial design.
Current Opinion in Neurology · 1999 · 26 citations
Pathogenesis of amyotrophic lateral sclerosis: a critical review
AbstractAmyotrophic lateral sclerosis is a neurodegenerative disease with unknown pathogenesis. It is a relatively common disorder of adults (2-4 per 100,000 incidence) and leads to death from respiratory failure. There is no cure at this time, and available treatment and management can at best extend survival to a modest degree. Increasing our understanding of the pathogenesis of this disease is essential to the development of more effective treatments. The level of research interest is very high, and yearly reviews of the literature are helpful in assessing progress.
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.
Symptomatic care of patients with amyotrophic lateral sclerosis
AbstractUntil a definitive treatment is found for amyotrophic lateral sclerosis, there will continue to be a need to provide symptomatic care. Experience with caring for a large number of patients has proved that symptomatic therapy can be based on rational principles. Treatment should be limited to procedures that are simple and low-cost, with low risk of serious morbidity. When all remedies fail, the physician can still provide a comforting presence and foster a dignified death. (<i>JAMA</i>234:715-717, 1975)
Journal of Clinical Neuromuscular Disease · 2022 · 0 citations
What Is in the Literature
AbstractABSTRACT: This issue of What Is in the Literature focuses on articles on amyotrophic lateral sclerosis over the past year. Amyotrophic lateral sclerosis remains a challenging disorder with progression to death. Within the past year, a phase 2 trial of a drug combination showed slowing in the rate of progression. While awaiting a phase 3 trial or approval by the Food and Drug Administration, selected articles that aid the diagnosis, contribute to care, or add to general knowledge about the disease are reviewed.
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.
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