DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lateral sclerosis — 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 moduleLateral sclerosis 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 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.
What the evidence adds up to
Ten years after riluzole was approved for amyotrophic lateral sclerosis, no other effective therapies had emerged, according to a 2007 review of then-current phase I, II and III trials. That review emphasised the scientific evidence behind each drug being tested and the importance of trial design. For primary lateral sclerosis, a 2020 review noted that the disease is extremely rare, not necessarily life-shortening, but causes substantial disability; improved symptomatic treatments, particularly for refractory spasticity, were described as a major unmet need, and progress in clinical trials for both symptomatic and disease-modifying therapy was reported.
A 2024 systematic review with meta-analysis examined 18 randomised clinical trials conducted between 2016 and 2021 that lasted six months or longer and used the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised as the outcome measure. The review included 4,214 participants: 1,880 received a drug and 1,933 received placebo, with about 30% discontinuing. Mean age was 57 years, 65% were male, 21.4% had bulbar onset and 77.0% had spinal onset. Of 15 drugs tested, edaravone, Relyvrio and masitinib showed positive effects if administered before severe functional impairment. However, a recent study failed to achieve Relyvrio’s primary goal of slowing the decline in ALSFRS-R scores compared with placebo. Two studies raised concerns about blinding, including only patients and investigators, and had high discontinuation rates. The funnel plot and Egger’s test showed no publication bias, but subgroup analysis found that substantial heterogeneity was significantly greater in published articles than in unpublished studies.
What is still missing is a clear understanding of which patients might benefit from which drug, given the great clinical variability between patients noted in the meta-analysis. The high discontinuation rate and the failure of Relyvrio to meet its primary endpoint in a recent study underscore the difficulty of translating early positive signals into robust trial results. Adequate funding for trials that can stratify patients by disease stage and onset type, and that maintain blinding and low dropout rates, remains a prerequisite for any future progress.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · 2020 · 8 citations · open access
Clinical care and therapeutic trials in PLS
AbstractPrimary lateral sclerosis (PLS) is an extremely rare central nervous system degenerative disorder characterized by slowly progressive upper motor neuron loss leading to severe limb and bulbar dysfunction and disability. Although not necessarily life-shortening, PLS disease burden is substantial and improved symptomatic treatments are a major unmet need, especially for the often refractory spasticity that is a core feature of the syndrome. In Section 1, we describe clinical care needs and emphasize a highly personalized approach that can be best attained through multidisciplinary management. In Section 2, we describe progress in clinical trials in PLS that includes advances in symptomatic treatment, disease-modifying therapy, and emerging innovative trials.
A SYSTEMATIC REVIEW WITH META-ANALYSIS ON THE EFFICACY OF RANDOMIZED CLINICAL TRIALS IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS USING THE FINAL SCORE ON THE AMYOTROPHIC LATERAL SCLEROSIS FUNCTIONAL RATING SCALE-REVISED AS THE OUTCOME MEASURE.
AbstractIn recent years there has been a significant increase in clinical trials to discover new medications that can slow the progression of Amyotrophic Lateral Sclerosis. The objective of this study was to carry out a systematic review with meta-analysis of randomized clinical trials lasting six or more months to evaluate the efficacy of treatments in patients with Amyotrophic Lateral Sclerosis carried out between 2016 and 2021, using the final score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. The search for articles covered the main databases in addition to the ClinialTrials.gov website and in the end, 18 studies were selected for analysis. In total, 4.214 participants were enrolled, 1.880 received the drug and 1.933 received the placebo, and about 30,0% discontinued over the course of the studies. The average age was 57 years old, with a predominance of males (65,0%) and 21,4% of participants had the onset of symptoms in the bulbar region and 77,0% in the spinal region. Reading the articles also revealed great clinical variability between patients. Of the 15 drugs that were tested, Edaravone, Relyvrio and Masitinib showed positive effects if they were administered before severe functional impairment. However, a recent study failed to achieve Relyvrio's primary goal of slowing the decline in ALSFRS-R scores compared with placebo. In the methodological analysis, two studies presented some concerns due to blinding, including only patients and investigators, and had high discontinuation rates. The funnel plot and Egger's regression test showed no publication bias. Subgroup analysis showed that substantial heterogeneity of the studies included in the analysis was significantly greater in the group of published articles as opposed to the unpublished studies.
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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