DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for neurodegenerative disease — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNeurodegenerative disease maps to a 46-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
approvedBosutinibApproved drug
Structures already discussed alongside neurodegenerative disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
human Src kinase — Bosutinib has a real, experimentally solved structure in complex with this target (PDB 4MXO, 2.105 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet db8drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4MXO · 2.105 Å · ligand Bosutinib (DB8). Experimental structure, not a prediction.
What the evidence adds up to
No neurodegenerative disease is currently curable, and available treatments only manage symptoms or slow progression. Drug repurposing is one strategy for finding new therapies, since the safety profiles of existing drugs are already known and the investment is lower than for de novo drug development. Several studies have examined old drugs for Alzheimer’s, Parkinson’s, Huntington’s, multiple sclerosis, and amyotrophic lateral sclerosis (ALS), but the abstracts provide no efficacy data from those studies.
Brain banking remains essential for studying neurodegenerative diseases. Postmortem tissue confirms clinical diagnoses and reveals pathological hallmarks such as protein aggregates. Genetic discoveries have redefined disease classifications, with overlapping pathologies now grouped as synucleinopathies or tauopathies. Banking methods must accommodate molecular experiments, and DNA screening raises new ethical issues. Characterisation in the post-genomic era requires genotype, phenotype, clinical data, and brain bank records.
A phase 2 protocol for bosutinib in ALS has been published. The drug is a Src/c-Abl inhibitor identified by induced pluripotent stem cell-based repurposing. A phase 1 study confirmed safety and tolerability over 12 weeks. The phase 2 study is open-label and multicentre, with a 12-week observation period, a 1-week transition, 24 weeks of treatment, and 4 weeks of follow-up. Only patients whose ALSFRS-R score declined by 1 to 4 points during observation will receive bosutinib. Twenty-five patients will be enrolled: 12 in the 200 mg once-daily group and 13 in the 300 mg once-daily group. Efficacy will be assessed by comparing ALSFRS-R scores with external published data from an edaravone study and registry data from a Japanese ALS cohort. The study is registered but results are not yet reported.
What is still missing is any evidence that bosutinib slows disease progression in ALS. The phase 2 results have not been published, so efficacy remains unknown. The trial uses external historical controls rather than a placebo arm, which may limit the reliability of comparisons. No repurposed drug has yet shown efficacy in a randomised controlled trial for any neurodegenerative disease in these abstracts. Funding for larger trials, better patient stratification, and placebo-controlled designs are still needed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pharmaceuticals · 2018 · 351 citations · open access
Old Drugs as New Treatments for Neurodegenerative Diseases
AbstractNeurodegenerative diseases are increasing in number, given that the general global population is becoming older. They manifest themselves through mechanisms that are not fully understood, in many cases, and impair memory, cognition and movement. Currently, no neurodegenerative disease is curable, and the treatments available only manage the symptoms or halt the progression of the disease. Therefore, there is an urgent need for new treatments for this kind of disease, since the World Health Organization has predicted that neurodegenerative diseases affecting motor function will become the second-most prevalent cause of death in the next 20 years. New therapies can come from three main sources: synthesis, natural products, and existing drugs. This last source is known as drug repurposing, which is the most advantageous, since the drug’s pharmacokinetic and pharmacodynamic profiles are already established, and the investment put into this strategy is not as significant as for the classic development of new drugs. There have been several studies on the potential of old drugs for the most relevant neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Multiple Sclerosis and Amyotrophic Lateral Sclerosis.
Current Opinion in Neurology · 2003 · 22 citations
Brain banking for neurodegenerative diseases
AbstractPURPOSE OF REVIEW: Brain banking remains a necessity for the study of neurodegenerative diseases. While the characterization of pathology observed at autopsy confirms clinical diagnosis, the structure and contents of pathological hallmarks are the starting point from which disease pathogenesis may be elucidated. Traditional neuropathology has served to define, characterize, and diagnose neurodegenerative diseases, accompanied by clinical presentation. The pathological substrates are then studied for their role in how they cause dysfunction in disease, or how their accumulation is presumably damaging. RECENT FINDINGS: New genetic findings have revolutionized these studies and have prompted a reexamination of traditional pathological definitions of disease. Many familial genetic mutations have been found, encoding proteins such as synuclein, parkin, tau, and others, creating genetic ways to define neurodegenerative diseases. Many of these proteins are components of aggregates, thus the ability to label these proteins has revealed new pathological characteristics that must be standardized. More complicating is that many proteins genetically linked to clinically distinct diseases are involved in overlapping neuropathology of what now appears to be a spectrum of diseases: 'synucleinopathies', 'tauopathies', and so on. Moreover, as genetic discoveries fuel molecular experiments on brain tissue, banking methods must now accommodate these techniques. Lastly, DNA screening involves ethical issues beyond those which were previously considered with postmortem tissue banking. SUMMARY: As more proteins are linked to disease, more is revealed about the underlying causative mechanisms, exposing points for interventions. To achieve this end, characterization for neurodegenerative disease in the post genomic era must include genotype, phenotype and clinical characterization, and postmortem brain banking data which includes these.
Protocol for a phase 2 study of bosutinib for amyotrophic lateral sclerosis using real-world data: induced pluripotent stem cell-based drug repurposing for amyotrophic lateral sclerosis medicine (iDReAM) study
AbstractINTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive, severe neurodegenerative disease caused by motor neuron death. Development of a medicine for ALS is urgently needed, and induced pluripotent cell-based drug repurposing identified a Src/c-Abl inhibitor, bosutinib, as a candidate for molecular targeted therapy of ALS. A phase 1 study confirmed the safety and tolerability of bosutinib in a 12-week treatment of ALS patients. The objectives of this study are to evaluate the efficacy and longer-term safety of bosutinib in ALS patients. METHODS AND ANALYSIS: An open-label, multicentre phase 2 study was designed. The study consisted of a 12-week observation period, a 1-week transitional period, a 24-week study treatment period and a 4-week follow-up period. Following the transitional period, patients whose total Revised ALS Functional Rating Scale (ALSFRS-R) score declined by 1 to 4 points during the 12-week observation period were to receive bosutinib for 24 weeks. In this study, 25 ALS patients will be enrolled; patients will be randomly assigned to the following groups: 12 patients in the 200 mg quaque die (QD) group and 13 patients in the 300 mg QD group of bosutinib. The safety and exploratory efficacy of bosutinib in ALS patients for 24 weeks will be assessed. Efficacy using the ALSFRS-R score will be compared with the external published data from an edaravone study (MCI186-19) and registry data from a multicentre ALS cohort study, the Japanese Consortium for Amyotrophic Lateral Sclerosis Research. ETHICS AND DISSEMINATION: This study was approved by the ethics committees of Kyoto University, Tokushima University, Kitasato University, Tottori University, Nara Medical University School of Medicine, Toho University and Hiroshima University. The findings will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: jRCT2051220002; Pre-results, NCT04744532; Pre-results.
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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