DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for amyotrophic lateral sclerosis — screening already-approved drugs against its 45-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 maps to a 45-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 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
angiogenin (ANG) — ANG 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 -drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AOH · 1.041 Å · ligand D(-)-TARTARIC ACID (TAR). Experimental structure, not a prediction.
What the evidence adds up to
A 1991 study of 23 families with familial amyotrophic lateral sclerosis found linkage of a causative gene to DNA markers on the long arm of chromosome 21, with a maximum lod score of 5.03. The same study reported a significant probability (P less than 0.0001) of genetic-locus heterogeneity among the families, meaning different families carried different genetic defects. A 2023 review states that despite years of research, the cause of amyotrophic lateral sclerosis remains unexplained, and the disease is likely due to a combination of mechanisms involving complex interactions between molecular and genetic pathways.
By 2007, ten years after the approval of riluzole, no other effective therapies had emerged. A 2017 review noted that no treatment existed for amyotrophic lateral sclerosis at that time, though edaravone had recently been approved in Japan and was pending approval in the USA. The same review described drug repurposing as playing an important role, with some repurposed compounds in late-stage clinical trials. A 2020 review discussed the rationale for repurposing older drugs developed for other diseases to target molecular and cellular processes compromised in amyotrophic lateral sclerosis, but did not report results from any such repurposed drug in patients.
What remains missing is a clear understanding of the disease mechanisms sufficient to identify reliable therapeutic targets, as the 2023 review emphasises that the interaction between multiple cellular processes makes it difficult to identify causative factors. No repurposed drug has yet demonstrated efficacy in a definitive phase III trial for amyotrophic lateral sclerosis, and the field still lacks a validated biomarker to stratify patients or to serve as a surrogate endpoint. Adequate funding for large, well-designed trials that account for genetic heterogeneity is also absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 1991 · 380 citations · open access
Linkage of a Gene Causing Familial Amyotrophic Lateral Sclerosis to Chromosome 21 and Evidence of Genetic-Locus Heterogeneity
AbstractBACKGROUND: Amyotrophic lateral sclerosis is a progressive neurologic disorder that commonly results in paralysis and death. Despite more than a century of research, no cause of, cure for, or means of preventing this disorder has been found. In a minority of cases, it is familial and inherited as an autosomal dominant trait with age-dependent penetrance. In contrast to the sporadic form of amyotrophic lateral sclerosis, the familial form provides the opportunity to use molecular genetic techniques to localize an inherited defect. Furthermore, such studies have the potential to discover the basic molecular defect causing motor-neuron degeneration. METHODS AND RESULTS: We evaluated 23 families with familial amyotrophic lateral sclerosis for linkage of the gene causing this disease to four DNA markers on the long arm of chromosome 21. Multipoint linkage analyses demonstrated linkage between the gene and these markers. The maximum lod score--5.03--was obtained 10 centimorgans distal (telomeric) to the DNA marker D21S58. There was a significant probability (P less than 0.0001) of genetic-locus heterogeneity in the families. CONCLUSIONS: The localization of a gene causing familial amyotrophic lateral sclerosis provides a means of isolating this gene and studying its function. Insight gained from understanding the function of this gene may be applicable to the design of rational therapy for both the familial and sporadic forms of the disease.
Intrathecal administration of natural human nterferon alpha in amyotrophic lateral sclerosis
AbstractTen patients with amyotrophic lateral sclerosis were given intrathecal injections of natural interferon alpha, 1 million units weekly for 7 to 24 weeks. Six patients completed the trial. Four voluntarily withdrew after 7 to 13 injections. The slopes of deterioration for 40 quantitative tests of neuromuscular function for the control and treatment periods were compared by paired t test in the six patients who completed the trial and in the patient who withdrew after 13 injections. No significant differences were found. The patients tolerated treatment well. The CSF reaction was modest and spontaneously reversible. Indomethacin and ibuprofen blocked interferon side effects.
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.
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.
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.
International Journal of Frontiers in Medicine · 2022 · 0 citations · open access
Sporadic amyotrophic lateral sclerosis: a case report and literature review
AbstractTo summarize the clinical features of a case of sporadic amyotrophic lateral sclerosis (SALS), improve the ability of early diagnosis and differential diagnosis, and summarize the treatment experience. [Methods] The clinical data of a case of sporadic amyotrophic lateral sclerosis (SALS) in our hospital were analyzed, and the diagnosis and treatment experience was summarized according to its history, clinical manifestations, and imaging and electromyogram manifestations, combined with relevant literature reports at home and abroad. [Results] After comprehensive treatment, the patient was in stable condition and discharged without any progress. After discharge, the patient continued to follow up. Although the systemic symptoms progressed, the degree was slight. [Conclusion] The etiology and pathogenesis of SALS are very complex, and the disease continues to progress. At present, there is no particularly effective treatment for this kind of disease. Comprehensive treatment can be adopted to control the development of the disease, so as to better improve the quality of life and survival rate of 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.
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