DeCure for Autosomal dominant optic atrophy, classic form
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant optic atrophy, classic form — 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 moduleAutosomal dominant optic atrophy, classic form 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 autosomal dominant optic atrophy, classic form 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
dynamin 1L (DNM1L) — DNM1L 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 8T1H · 5.97 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 755 unrelated probands with bilateral optic atrophy, genetic screening of the OPA1 gene found putatively pathogenic variants in 278 individuals, or 36.8% of the cohort. 156 unique variants were identified, 78% of which were null alleles. One variant, c.2708_2711del/p.(V903Gfs*3), accounted for 14% of all disease-causing alleles. 48 variants were novel; of these, nine were classified as pathogenic, 34 as likely pathogenic, and five as variants of uncertain significance. Splicing analysis of patient blood samples and minigene assays revealed exon skipping, activation of cryptic splice sites, and inclusion of pseudoexons.
One family with 20 affected members across three generations showed autosomal dominant transmission of optic atrophy with a clear bimodal distribution of severity. Four male patients had severe impairment of vision since childhood, while 16 other subjects (seven males and nine females) were completely asymptomatic. This suggests a sex-influenced severity in some pedigrees. In another family spanning three generations, two of three patients with dominant optic atrophy also had mild sensorineural hearing loss, an association that has been rarely reported.
No drug treatment was studied in any of these reports. The abstracts describe genetic characterisation and natural history, not intervention. There is no evidence from these papers that any drug can alter the course of autosomal dominant optic atrophy.
What is still missing is any clinical trial testing a drug in this condition, any funding for such a trial, and any stratification of patients by specific OPA1 variant type or by sex to account for the variable severity seen in some families.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2021 · 37 citations · open access
Mutation spectrum of the OPA1 gene in a large cohort of patients with suspected dominant optic atrophy: Identification and classification of 48 novel variants
AbstractAutosomal dominant optic atrophy is one of the most common inherited optic neuropathies. This disease is genetically heterogeneous, but most cases are due to pathogenic variants in the OPA1 gene: depending on the population studied, 32-90% of cases harbor pathogenic variants in this gene. The aim of this study was to provide a comprehensive overview of the entire spectrum of likely pathogenic variants in the OPA1 gene in a large cohort of patients. Over a period of 20 years, 755 unrelated probands with a diagnosis of bilateral optic atrophy were referred to our laboratory for molecular genetic investigation. Genetic testing of the OPA1 gene was initially performed by a combined analysis using either single-strand conformation polymorphism or denaturing high performance liquid chromatography followed by Sanger sequencing to validate aberrant bands or melting profiles. The presence of copy number variations was assessed using multiplex ligation-dependent probe amplification. Since 2012, genetic testing was based on next-generation sequencing platforms. Genetic screening of the OPA1 gene revealed putatively pathogenic variants in 278 unrelated probands which represent 36.8% of the entire cohort. A total of 156 unique variants were identified, 78% of which can be considered null alleles. Variant c.2708_2711del/p.(V903Gfs*3) was found to constitute 14% of all disease-causing alleles. Special emphasis was placed on the validation of splice variants either by analyzing cDNA derived from patients´ blood samples or by heterologous splice assays using minigenes. Splicing analysis revealed different aberrant splicing events, including exon skipping, activation of exonic or intronic cryptic splice sites, and the inclusion of pseudoexons. Forty-eight variants that we identified were novel. Nine of them were classified as pathogenic, 34 as likely pathogenic and five as variant of uncertain significance. Our study adds a significant number of novel variants to the mutation spectrum of the OPA1 gene and will thereby facilitate genetic diagnostics of patients with suspected dominant optic atrophy.
Familial Optic Atrophy with Sex-Influenced Severity
AbstractA family is described with 20 members in three successive generations affected by optic atrophy without other ocular or extraocular manifestations. The anomaly was transmitted as an autosomal-dominant character. There was a clearly bimodal distribution of severity: 4 male patients complained of severe impairment of vision since childhood while 16 other subjects (7 males and 9 females) were completely asymptomatic. This family could be an example of a new variety of autosomal dominant optic atrophy characterized by sex-influenced severity.
Dominant optic atrophy and sensorineural hearing loss
AbstractThe authors report three patients belonging to three generations of the same family presenting with a dominant optic atrophy; two of these patients (grandfather, mother) also suffered from a mild hearing loss. This association has been rarely reported and suggests to perform a systematic otologic screening in every patient presenting with an hereditary optic atrophy.
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.
