DeCure for Frontotemporal dementia and/or amyotrophic lateral sclerosis 4
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for frontotemporal dementia and/or amyotrophic lateral sclerosis 4 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFrontotemporal dementia and/or amyotrophic lateral sclerosis 4 maps to a 2-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 frontotemporal dementia and/or amyotrophic lateral sclerosis 4 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
TANK binding kinase 1 (TBK1) — TBK1 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 5-cyclopropyl-2-{[3-(morpholin-4-ylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4IM0 · 2.4001 Å · ligand N-{3-[(5-cyclopropyl-2-{[3-(morpholin-4-ylmethyl)phenyl]amino}pyrimidin-4-yl)amino]propyl}cyclobutanecarboxamide (1FV). Experimental structure, not a prediction.
What the evidence adds up to
Frontotemporal dementia is described as the third most common cause of dementia across all ages and the most common cause of early onset dementia before age 65. Up to 40% of patients have a family history, with autosomal dominant inheritance seen in a quarter of those familial cases. A 1999 case report describes a patient with rapidly progressive dementia alongside clinical features of amyotrophic lateral sclerosis. Magnetic resonance imaging showed frontal and left temporal atrophy, and single photon emission computed tomography revealed reduced tracer uptake in the frontotemporal lobes. Neuropathological examination found mild frontotemporal atrophy with spongiform changes and neuronal loss mainly in layers II and III of the frontotemporal cortices, atrophy of the hypoglossal nuclei, and spinal cord changes consistent with motor neuron disease. The patient’s course was irreversible and progressive.
A 2019 review notes that several genes and cellular processes implicated in amyotrophic lateral sclerosis have also been linked to frontotemporal dementia, suggesting shared origins with varied clinical presentations. The review states that scientists are rapidly identifying ALS/FTD suppressors that act on conserved pathways from invertebrates to vertebrates to alleviate degeneration. These genetic modifiers are said to provide insight into molecular pathways and reveal new targets for therapeutic development. The 2020 review describes key genes whose mutations can result in frontotemporal dementia, the possible pathogenic mechanisms, and clinical features for different genetic variants, with emphasis on the frontotemporal dementia phenotype associated with amyotrophic lateral sclerosis.
No drug is mentioned in any of the three abstracts. No concrete numbers for survival, response rates, or sample sizes are given. The 1999 case report documents an irreversible and progressive course in a single patient. The 2019 review describes the identification of genetic suppressors in model organisms but provides no human trial data. What is still missing is any clinical trial testing a specific compound in patients, any evidence of disease modification in humans, and any stratification of patients by the genetic variants described in the reviews.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Molecular Biology · 2020 · 40 citations
Genetic Diversity in Frontotemporal Dementia
AbstractFrontotemporal dementia is a progressive neurodegenerative disorder with high clinical, genetic, and pathomorphological diversity It is the third most common cause of dementia in all ages and the most common cause of early onset dementia (below 65). Despite its multifactorial nature, up to 40% of patients have a family history where the autosomal dominant inheritance type is seen in a quarter of cases. In this review, we describe key genes whose mutations can result in the development of frontotemporal dementia, the possible pathogenic mechanisms of the degenerative process, and provide information on the clinical features of the disease for different genetic variants. Special emphasis is placed on the frontotemporal dementia phenotype that is associated with amyotrophic lateral sclerosis.
Journal of Neuroscience · 2019 · 16 citations · open access
Phenotypic Suppression of ALS/FTD-Associated Neurodegeneration Highlights Mechanisms of Dysfunction
AbstractA fundamental question regarding the etiology of amyotrophic lateral sclerosis (ALS) is whether the various gene mutations associated with the disease converge on a single molecular pathway or act through multiple pathways to trigger neurodegeneration. Notably, several of the genes and cellular processes implicated in ALS have also been linked to frontotemporal dementia (FTD), suggesting these two diseases share common origins with varied clinical presentations. Scientists are rapidly identifying ALS/FTD suppressors that act on conserved pathways from invertebrates to vertebrates to alleviate degeneration. The elucidation of such genetic modifiers provides insight into the molecular pathways underlying this rapidly progressing neurodegenerative disease, while also revealing new targets for therapeutic development.
Arquivos de Neuro-Psiquiatria · 1999 · 5 citations · open access
Amyotrophic lateral sclerosis with dementia: case report
AbstractA patient is described in whom a profound and rapidly progressive dementia occurred in association with clinical features of amyotrophic lateral sclerosis. A magnetic resonance imaging showed signs of frontal and especially left temporal atrophy. The pattern of dementia indicated impaired frontotemporal lobe functions, evidenced by reduced tracer uptake in the frontotemporal lobes on brain single photon emission computed tomography. Neuropathological examination in this patient revealed mild frontotemporal atrophy with spongiform changes and neuronal loss affecting mainly layers II and III of the frontotemporal cortices. There was atrophy of the hypoglossal nuclei. The spinal cord changes were consistent with motor neuron disease. The patient showed an irreversible and progressive course. A review of the relevant literature was made.
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.
