DeCure for Frontotemporal dementia and/or amyotrophic lateral sclerosis 1
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for frontotemporal dementia and/or amyotrophic lateral sclerosis 1 — screening already-approved drugs against its 3-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 1 maps to a 3-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 1 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
transmembrane protein 106B (TMEM106B) — TMEM106B 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 8OTD · 2.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The C9orf72 repeat expansion is the most common genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Two competing disease mechanisms have been proposed: a gain of function from toxic repeat RNA and dipeptide repeat proteins, and a loss of function from reduced C9orf72 protein levels. Patient brain tissue shows both RNA foci and protein aggregates, supporting gain of function, while reduced C9orf72 levels and its role in endocytic and autophagic pathways support loss of function. As of 2014, the weight of evidence favoured gain of function as the primary mechanism, and antisense oligonucleotides targeting C9orf72 had shown promise in preclinical models for reducing gain-of-function toxicity.
A 2019 review noted that multiple ALS-associated genes and cellular processes also appear in FTD, suggesting shared molecular origins. Researchers have identified genetic suppressors of ALS/FTD neurodegeneration that act on conserved pathways from invertebrates to vertebrates, but no specific drug or compound was tested in that review. A 2021 case report described a single patient with behavioural variant FTD who developed progressive upper limb weakness, impaired memory, dysphagia, and prosopagnosia, illustrating the clinical overlap between the two conditions but providing no treatment data.
No clinical trial has tested any drug specifically for C9orf72-associated ALS/FTD in a randomised, controlled setting. The antisense oligonucleotide approach mentioned in 2014 has not yet produced published phase 3 results. What is missing is a completed, adequately powered trial that stratifies patients by C9orf72 repeat expansion status, and sufficient funding to move preclinical suppressors and antisense therapies through human testing.
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 · 2014 · 71 citations · open access
C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia
AbstractPURPOSE OF REVIEW: The molecular mechanisms that underlie chromosome 9 open reading frame 72 (C9orf72)-associated amyotrophic lateral sclerosis and frontotemporal dementia are rapidly emerging. Two potential disease mechanisms have been postulated - gain or loss of function. We provide an overview of recent advances that support or oppose gain-of-function and loss-of-function mechanisms. RECENT FINDINGS: Since the discovery that a noncoding repeat expansion in C9orf72 was responsible for chromosome 9-linked amyotrophic lateral sclerosis and frontotemporal dementia in 2011, a plethora of studies have investigated clinical, pathological and mechanistic aspects of the disease. Loss of function is supported by reduced levels of C9orf72 in patient brain and functional work, revealing a role of the C9orf72 protein in endocytic and autophagic pathways and motor function. Gain of function is supported by the presence in patient brain of both repeat RNA and protein aggregates. Repeat RNA aggregates termed RNA foci, a hallmark of noncoding repeat expansion diseases, have been shown to sequester proteins involved in RNA splicing, editing, nuclear export and nucleolar function. Repeat-associated non-ATG dependent translation gives rise to toxic dipeptide repeat proteins that form inclusions in patient tissue. Antisense oligonucleotides targeting C9orf72 have shown promise for combating gain-of-function toxicity. SUMMARY: Rapid progress is being made towards understanding this common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Overall, the weight of data currently sits in favour of gain of function as the most important disease mechanism, which has important implications for the development of effective and targeted therapies.
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.
Archives of Mental Health · 2021 · 0 citations · open access
A rare case of frontotemporal dementia with amyotrophic lateral sclerosis
AbstractFrontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive degeneration of the frontal and temporal lobes which typically presents with cognitive symptoms. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons, leading to symptoms of motor weakness. We present a case of behavioral variant of FTD with ALS. The patient presented with changes in his behavior followed by impaired memory and progressive weakness of bilateral upper limbs. Patient eventually developed difficulty swallowing and recognizing faces too. The case highlights the association between FTD and ALS.
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.
