DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for amyotrophic lateral sclerosis type 22 — 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 22 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 22 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
Despite decades of research, no disease-modifying therapy for amyotrophic lateral sclerosis has reached the clinic beyond riluzole, which has only marginal effects on survival. A 2005 review noted that a number of established agents, including beta-lactam antibiotics and minocycline, had been re-investigated as potential neuroprotective drugs, but cautioned that there had been a long-standing failure to successfully transfer therapeutic compounds to the clinic. By 2007, ten years after riluzole’s approval, there were still no other effective therapies, though the number of potential agents in Phase I, II and III trials was increasing. A 2015 review described the initial enthusiasm for transgenic mouse models as disappointing, stating that monogenic models may have masked the true complexity of the human disease, and that ALS had evolved into a multisystem disorder.
Antibody-based strategies have been explored in preclinical models. In 2011, researchers reported that several monoclonal antibodies recognising only misfolded SOD1, but not the wild-type protein, had been generated, and that some delayed disease progression in mutant SOD1 transgenic mice when delivered intraventricularly. The authors noted that determining the pathogenic domain was crucial for the antibody’s effect, and that single-chain fragment of variance of IgG (scFv) was attracting attention for its potential to target intracellular proteins. However, these findings remain confined to animal models, with no translation to human trials reported in the provided abstracts.
The cause of ALS remains unexplained, and a 2023 review stated that the disease is likely due to a combination of mechanisms involving complex interactions between molecular and genetic pathways, making it difficult to identify causative factors. A 2020 review described efforts to repurpose “old” drugs for ALS, targeting molecular and cellular processes compromised in the disease, but provided no specific efficacy data from clinical trials. Across all abstracts, no concrete response rates, survival improvements, or sample sizes from human studies are given for any repurposed drug. What is still missing is a successful translation of preclinical findings into clinically meaningful outcomes, adequate funding for large-scale trials, and a trial design that accounts for the heterogeneity of the disease rather than treating it as a single entity.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Neurology Neurosurgery & Psychiatry · 2015 · 129 citations · open access
The expanding syndrome of amyotrophic lateral sclerosis: a clinical and molecular odyssey
AbstractRecent advances in understanding amyotrophic lateral sclerosis (ALS) have delivered new questions. Disappointingly, the initial enthusiasm for transgenic mouse models of the disease has not been followed by rapid advances in therapy or prevention. Monogenic models may have inadvertently masked the true complexity of the human disease. ALS has evolved into a multisystem disorder, involving a final common pathway accessible via multiple upstream aetiological tributaries. Nonetheless, there is a common clinical core to ALS, as clear today as it was to Charcot and others. We stress the continuing relevance of clinical observations amid the increasing molecular complexity of ALS.
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.
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.
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.
Rinsho Shinkeigaku · 2011 · 0 citations · open access
Antibody therapy targeting ALS-linked misfolded protein
AbstractAccumulating evidence indicates that the pathogenesis of Amyotrophic lateral sclerosis (ALS) is tightly linked to misfolding a key protein. Antibody therapy aims to eliminate or compete with the pathogenic proteins, through either passive or active immunization. We and others have generated several monoclonal antibodies (MAb)s which recognize only misfolded SOD1, but not the wild-type. Several MAbs are reported to delay the progression of mutant SOD1 Tg mice by the intraventricular application, which is mediated by different pathways. The determination of the pathogenic domain is crucial to acquire the effect of MAb therapy. Single chain of fragment of variance of IgG (scFv) is attracting emerging attention due to its broad application, in which intracellular proteins can be targeted by Intrabody or the modification of MAb with translocation signals.
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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