DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for Alzheimer disease 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 moduleAlzheimer disease 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 alzheimer disease 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
ADAM metallopeptidase domain 10 (ADAM10) — ADAM10 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 n-hydroxyaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ESV · 3.3 Å · ligand 4-(N-HYDROXYAMINO)-2R-ISOBUTYL-2S-(2-THIENYLTHIOMETHYL)SUCCINYL-L-PHENYLALANINE-N-METHYLAMIDE (BAT). Experimental structure, not a prediction.
What the evidence adds up to
Existing treatments for Alzheimer’s disease slow symptom progression for an average of only six months, and their efficacy does not extend to all patients. As of 2012, only three therapies were being investigated in Phase III clinical trials, a situation the authors describe as reflecting substantial caution and underinvestment in treatment development. The disease has a long preclinical period of roughly 20 years and is characterised neuropathologically by amyloid-beta plaques and aggregated tau tangles.
Drug repurposing has been proposed as a strategy to address the high rate of clinical trial failures. A 2021 literature review identified allopurinol, bromocriptine, bupropion, raloxifene, thalidomide, and zidovudine as drugs that may have potential to treat Alzheimer’s disease, but the authors state these drugs need to be studied further. By 2016, the Alzheimer’s Drug Discovery Foundation was supporting 18 approved drugs in repurposing trials, and the total number of approved drugs being studied in repurposing trials for Alzheimer’s had reached at least 127. Drugs discussed at a 2016 press briefing included tadalafil and levetiracetam.
Evaluating treatment effectiveness in Alzheimer’s disease is often surprisingly difficult. Biomarkers might offer a quantifiable objective measure, but a 2011 paper argues they must meet criteria including biological plausibility, statistical significance, dose dependence, convergence across measures, and replicability. If biomarkers cannot meet these criteria, their usefulness may be limited to supplementing, not supplanting, clinical profiles of treatment effects. What remains missing is not a list of candidate drugs, but adequately powered, biomarker-informed clinical trials that can distinguish true disease modification from symptomatic effects, and the funding to conduct them.
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 Review of Neurotherapeutics · 2012 · 61 citations
New and emerging treatments for Alzheimer’s disease
AbstractAlzheimer's disease (AD) and other dementias represent a significant and increasing clinical challenge. This review highlights current treatment options for AD and the main focusses of therapies currently being evaluated in clinical trials and for future therapeutic development. Existing treatments slow the progression of symptoms of the disease, but their efficacy does not extend to all people with AD, and benefits are not conveyed beyond an average of 6 months. Despite the substantial economic cost and healthcare burden of AD, which is increasing as populations age, there are currently only three therapies being investigated in Phase III clinical trials. This emphasises the substantial caution and underinvestment in treatment development in this area and why it is critical to address the current lack of effective treatments to target the underlying pathology and disease process in Alzheimer's disease.
International Journal of Alzheimer s Disease · 2011 · 12 citations · open access
Biomarkers to Measure Treatment Effects in Alzheimer′s Disease: What Should We Look for?
AbstractIt is often surprisingly difficult to tell whether a treatment for Alzheimer's disease is effective. Biomarkers might offer the potential of a quantifiable objective measure of treatment effectiveness. This paper suggests several criteria by which biomarkers might be evaluated as outcomes measures. These include biological plausibility, statistical significance, dose dependence, convergence across measures, and replicability. If biomarkers can meet these criteria, then, pending regulatory approval, they may have a role in the evaluation of treatment effectiveness in Alzheimer's disease. If not, their usefulness may be in supplementing, but not supplanting, clinical profiles of treatment effects.
Drug repurposing strategy for treating Alzheimer’s disease
AbstractAbstract Background Alzheimer’s disease with a long preclinical period of ∼20 years is a chronic, insidious, and progressive neurodegenerative disease of old age. Neuropathologically AD is characterized by the presence of accumulated Amyloid‐beta in plaques (in extracellular spaces, and walls of blood vessels) and aggregated tau protein in neurofibrillary tangles. Drug repurposing is the search for new indications or molecular targets distinct from a drug’s acknowledged activity, pharmacological effect or binding specificities. With the ever‐increasing rates of termination of drugs in clinical trials, drug repositioning has risen as one of the effective solutions against the risk of drug failures. Method A comprehensive literature search was performed in the Pub Med/Science direct/Google scholar/Plos one databases and connected papers to review relevant articles in English, using keywords ‘‘Drug repurposing and neurological disorder, drug repurposing and dementia, drug repurposing and Alzheimer 'disease. The research papers were scrutinized and studied thoroughly. Result According to literature it has been found that some repurposed drugs i.e, Allopurinol, Bromocriptine, Bupropion, Raloxifene, Thalidomide, Zidovudine may have a potential to treat Alzheimer’s disease. Conclusion The repurposing drug approach may be used to treat Alzheimer’s and these drugs are needed to studied further.
Expert Opinion on Investigational Drugs · 2013 · 8 citations · open access
Is a potential Alzheimer's therapy already in use for other conditions? Can medications for hypertension, diabetes and acne help with the symptoms?
AbstractThere is an urgent need to develop and evaluate more effective pharmacological treatments for Alzheimer's disease (AD). This editorial explores the avenue of drug repositioning and outlines a number of existing treatments that show great promise as therapies, in addition to discussing the potential for high-throughput drug discovery techniques in this important field.
Approved drugs are to be studied for use in Alzheimer’s disease
AbstractMany drugs that have been approved by the Food and Drug Administration could be repurposed or used off label to treat Alzheimer’s disease, according to reports from the Alzheimer’s Drug Discovery Foundation conference in New Jersey.
The foundation is supporting 18 approved drugs in repurposing trials. This brings the total number of approved drugs that were being studied for use in treating Alzheimer’s disease in repurposing trials to at least 127, the foundation said.
The drugs discussed at a press briefing on 13 September were tadalafil (Cialis), approved to treat erectile dysfunction, and levetiracetam (Keppra), approved to …
O1‐02‐04: BASELINE CHARACTERICS FROM A PHASE 3 TRIAL OF CRENEZUMAB IN PRODROMAL TO MILD ALZHEIMER'S DISEASE (CREAD)
AbstractCrenezumab is a humanized anti-amyloid-beta (Aβ) monoclonal IgG4 antibody in development for Alzheimer's disease (AD). Crenezumab binds to multiple forms of Aβ, with high affinity for oligomers, blocking oligomer-induced neurotoxicity, and with low risk of amyloid-related imaging abnormalities (ARIA). Although Phase 2 co-primary endpoints were not met, exploratory analyses suggested that crenezumab should be tested for clinically meaningful efficacy at a higher dose and earlier disease stage. Data from a Phase 1b study that investigated the safety/tolerability of higher doses of crenezumab supported a 4-fold higher Phase 3 dose than used in Phase 2. Two global, randomized, double-blind, placebo-controlled, parallel-group Phase 3 studies (CREAD [NCT02670083]; CREAD2 [NCT03114657]) are testing the efficacy and safety of crenezumab (60 mg/kg) in patients with prodromal to mild AD. Here we describe the study design/methodology, and baseline characteristics from CREAD. Patients aged 50–85 years with prodromal to mild AD and confirmed evidence of cerebral amyloid pathology (CSF or amyloid PET) were enrolled. At screening, patients had an MMSE score of ≥22, a CDR-global score of 0.5 or 1, Free and Cued Selective Reminding Test (FCSRT) immediate free recall ≤27 and cueing index ≤0.67 (to enrich for patients with greater likelihood of progression over 105 weeks), and were randomized 1:1 to placebo or crenezumab (60 mg/kg q4w IV). Randomization was stratified by dementia and APOE status, baseline anti-dementia medications, and geographic region. Primary and secondary endpoints include change from baseline in CDR-SB, ADAS-Cog-13, and ADCS-ADL scores over 105 weeks. Exploratory objectives are to assess treatment effects on CSF biomarkers and amyloid- and tau-PET. MRI examinations are used to monitor safety and measure volumetric changes. The CREAD study has completed recruitment, with 813 patients enrolled. Baseline data will be presented. Building on learnings from Phase 2, the CREAD and CREAD2 Phase 3 trials are investigating the clinical efficacy of a 4-fold higher dose of crenezumab (vs. Phase 2) in prodromal to mild AD, and will test whether clinically meaningful efficacy can be achieved without the associated safety findings that have been described with other passive anti-amyloid immunotherapies targeting fibrillar amyloid in AD.
Alzheimer's Disease: A Physician's Guide to Practical Management
AbstractAlzheimer's Disease: A Physician's Guide to Practical Management
edited by R.W. Richter and B.Z. Richter, 479 pp., Humana Press, 2004, $99.50
The editors of this book have assembled an impressive cast of 74 authors, most of whom are well recognized authorities in the field, while some are very promising young scientists. It has 51 chapters arranged in 11 sections. It covers the traditional aspects of scientific background, epidemiology, clinical assessment, treatment options, late stage therapy, neuropsychiatric management, and family care issues. In addition, it covers some timely topics such as outcome measurement, the transitional stage before clinical Alzheimer disease (AD), prevention …
AbstractTreatment with the cholinesterase inhibitor tacrine and lecithin does not improve the symptoms of Alzheimer'sdisease and may induce hepatitis, researchers say. Following a report of beneficialeffects they performed a multicentre double blind, placebo controlled, crossovertrial involving 67 patients given a meanof ll4mg tacrine or placebo daily plus1,200mg lecithin for four weeks. Cognitive, behavioural and overall state weremeasured using rating scales.
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.
