DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for amyotrophic lateral sclerosis type 20 — 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 20 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 20 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
heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) — HNRNPA1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9GKF · 3.21 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Amyotrophic lateral sclerosis type 20 is a fatal motor neuron disorder for which no disease-modifying treatment exists. Riluzole remains the only approved therapy, and its effect on survival is only marginal. A 2005 review noted that despite intensive research, no other effective therapy had emerged in the ten years since riluzole’s approval. A 2017 review of clinical trials up to November 2016 confirmed that no treatment existed at that time, though edaravone had recently been approved in Japan and was pending in the United States. The same review identified drug repurposing as playing an important role, with some repurposed compounds having achieved orphan drug applications and reaching late-stage clinical development.
The underlying cause of ALS remains unexplained. A 2001 review stated that specific mechanisms had not been established, and a 2023 review reiterated that the cause is still unknown after years of research. The 2023 review proposed that ALS is likely not due to a single factor but to a combination of mechanisms involving complex interactions between molecular and genetic pathways, with multiple cellular processes and interactions between different mechanisms making it difficult to identify causative factors. A 2015 review cautioned that monogenic transgenic mouse models may have masked the true complexity of the human disease, and that initial enthusiasm for these models had not been followed by rapid advances in therapy or prevention.
Several compounds have been investigated without success. A 2005 review mentioned that beta-lactam antibiotics and minocycline had been re-investigated as potential neuroprotective agents, and that growth factors were being explored with advances in delivery systems. A 2007 review provided a systematic evaluation of drugs in Phase I, II and III trials, emphasising the need for scientific evidence supporting drug selection and for better trial design. The 2017 review grouped ongoing trials into biomarkers, biological therapies, cell therapy, drug repurposing, and new drugs, but noted multiple obstacles explaining the absence of effective drugs. The 2023 review discussed emerging treatment strategies but concluded that the journey to understanding or treating ALS is still a long one.
What is still missing is a clear understanding of the specific pathogenic mechanisms that could be targeted, particularly given the heterogeneity of the syndrome. Clinically relevant preclinical studies and better clinical trial design are needed, as the field has a long-standing failure to successfully transfer therapeutic compounds to the clinic. Patient stratification by genetic or molecular subtype may be necessary, but the necessary biomarkers and validated preclinical models are not yet established. Funding for large-scale, well-designed trials and for basic research into the complex interplay of multiple disease mechanisms remains insufficient.
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.
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.
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.
Neurorehabilitation and neural repair · 1994 · 4 citations · open access
Management of Patients with Amyotrophic Lateral Sclerosis
AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease that is often viewed as untreatable. Although no specific treatment for this disease is available, there are important treatable diseases to be considered in the differential and treatable conditions that co-exist or complicate the course of the illness. In this article, we review our current management of patients with ALS.
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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