DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for amyotrophic lateral sclerosis type 18 — 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 18 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 18 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
profilin 1 (PFN1) — PFN1 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6NBE · 2.0 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
Riluzole remains the only approved therapy for amyotrophic lateral sclerosis as of 2005, with only marginal effects on survival. A 2005 review notes that established agents including beta-lactam antibiotics and minocycline have been re-investigated for neuroprotective potential, and progress has been made in exploiting growth factors partly due to advances in delivery systems to the central nervous system. A novel class of compounds, heat-shock protein co-inducers, has been identified that upregulate cell stress responses. Non-drug therapies such as gene-silencing and stem cell therapies are also under development. The same review cautions that significant advances in understanding pathogenesis and developing new approaches have been accompanied by a long-standing failure to successfully transfer therapeutic compounds to the clinic.
A 2007 review states that no effective therapies other than riluzole existed ten years after its approval for amyotrophic lateral sclerosis. That review provides a systematic evaluation of drugs in Phase I, II and III clinical trials, with emphasis on the scientific evidence supporting each drug’s selection and on trial design. A separate 2005 review notes that the past decade of research contributed to a greater understanding of the disease process, development of relevant animal models, and identification of several therapeutic approaches that may delay disease progression.
A 2023 paper highlights that accurately tracking disease progression remains an ongoing challenge for research studies and in the clinic. The need for more reliable and responsive outcome measures is particularly important in ALS clinical trials, where modest treatment effects are evaluated in patient populations with heterogeneous phenotypes and rates of decline. The paper states that flawed outcome measures can miss real treatment effects or falsely suggest positive effects for ineffective therapies, potentially exposing patients to unnecessary costs and risks. The underlying causes of the disease are still not understood.
What is still missing is a clinically effective disease-modifying treatment that has successfully transferred from preclinical studies to the clinic, reliable outcome measures capable of detecting modest treatment effects in heterogeneous patient populations, and a full understanding of the underlying causes of the disease. The research community has identified a need for clinically relevant preclinical studies and better clinical trial design for amyotrophic lateral sclerosis, but these remain unmet requirements.
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.
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.
AJN American Journal of Nursing · 2022 · 22 citations
New Drug Approved For ALS
AbstractSodium phenylbutyrate-taurursodiol (Relyvrio) has been approved to treat amyotrophic lateral sclerosis.The drug was approved despite the absence of phase 3 clinical trial data. Data from a small phase 2 trial indicated that patients receiving Relyvrio had a slower loss of functioning than those taking placebo.Relyvrio poses a risk to patients who are sensitive to salt intake and to those with pancreatic, intestinal, and enterohepatic circulation disorders.
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.
AIMing for Better Tools to Track Disease Progression
AbstractDespite recent progress in amyotrophic lateral sclerosis (ALS) therapeutic development, accurately tracking disease progression remains an ongoing challenge for research studies and in the clinic. The need for more reliable and responsive outcome measures is particularly important in the setting of ALS clinical trials, where modest treatment effects are evaluated in patient populations with heterogenous phenotypes and rates of decline. At a time where underlying causes of disease are still not understood, yet stepwise progress toward new treatments is expected, flawed outcome measures have the ability to miss real treatment effects when they are actually present or can falsely suggest the presence of positive treatment effects for ineffective therapies, potentially exposing patients to unnecessary costs and risks.
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.
