DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for optic atrophy 9 — 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 moduleOptic atrophy 9 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 optic atrophy 9 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.
What the evidence adds up to
Optic nerve atrophy accounts for 60–68% of blindness and low vision cases worldwide, with causes including inflammatory and vascular diseases, glaucoma, atherosclerosis, intoxication, and congenital or hereditary conditions. A 2021 review summarises drug and non-drug treatment combined with physiotherapy but provides no specific efficacy data, survival rates, or response rates for any intervention.
Dominant optic atrophy (DOA), the commonest inherited form, maps to a 1.4-cM region at chromosome 3q28–q29. A 2001 study constructed a BAC contig covering roughly 3.3 Mb around the OPA1 critical region and corrected errors in marker order. Reassessment of the previously claimed founder haplotype, said to account for 95% of linked families, suggested the founder effect may not be as significant as originally thought. One known gene (KIAA0567) and 15 ESTs were found within the minimal disease region.
In 2023, two families of Jewish Ashkenazi descent with early-onset isolated bilateral optic atrophy were reported. Male siblings (three in one family, two in the other) had the condition; their mothers and one healthy sister showed mild signs, consistent with X-linked inheritance. Whole-exome sequencing identified two novel pathogenic variants in the WDR45 gene at the OPA2 locus (Xp11.23): a missense variant (c.107C>A, p.Pro36His) and a splice-site variant (c.236-1G>T). Both variants segregated fully with disease in all affected males and carrier females and were absent in unaffected participants. Two siblings also had mild learning disabilities and autism spectrum disorder. Variants in known optic atrophy genes had been excluded.
A 2022 review notes that optic neuropathy can accompany systemic neurodegenerative syndromes and that mutated genes disrupt encoded protein structure, affecting intracellular chemical reactions. It lists rare syndromes causing genetically inherited optic atrophy but provides no treatment outcomes or quantitative clinical data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Russian Annals of Ophthalmology · 2021 · 7 citations
Modern treatment of different forms of optic nerve atrophy
AbstractOptic nerve atrophy (ONA) is one of the most common causes of blindness and low vision in the world. The disease occurs in 60-68% of cases. The causes of optic nerve atrophy are diverse: inflammatory and vascular diseases of the optic nerve and retina, glaucoma, atherosclerosis of the main vessels of head and neck, diseases of central nervous system, intoxication of various etiologies, as well as congenital and hereditary diseases. The literature review presents data on the diagnosis and classification of optic nerve atrophy, as well as on drug and non-drug treatment in combination with physiotherapy.
Cytogenetic and Genome Research · 2001 · 4 citations
A high-density transcript map of the human dominant optic atrophy OPA1 gene locus and re-evaluation of evidence for a founder haplotype
AbstractDominant optic atrophy (DOA, gene OPA1) is the commonest form of inherited optic atrophy. Linkage studies have shown that a locus for this disease lies in a 1.4-cM region at chromosome 3q28-->q29 and have suggested a founder haplotype for as many as 95% of the linked families. To aid the identification of candidate genes for this disease, we have constructed a Bacterial Artificial Chromosome (BAC) contig covering approximately 3.3 Mb and encompassing the OPA1 critical region (flanking markers D3S3669 and D3S3562). This physical map corrects errors in the marker order reported in the literature, allowing the OPA1 critical region to be precisely defined. A reassessment of the founder effect in the light of the revised marker order suggests that it may not be as significant as had previously been suggested. A high-density transcript map was created by precisely mapping genes and expressed sequence tags (ESTs) from GeneMap'99, that have been loosely assigned to the region by radiation hybrid mapping. One known gene (KIAA0567 protein) and 15 ESTs were found to lie within the minimal disease region. Analysis of the sequence data already available from within the OPA1 critical region allowed the identification and mapping of a further 31 ESTs. The work presented in this study provides the basis for the characterisation of candidate genes and the ultimate identification of the gene mutated in DOA.
Variants in the <i>WDR45</i> Gene Within the OPA-2 Locus Associate With Isolated X-Linked Optic Atrophy
AbstractPurpose: To describe clinical and molecular findings of two families with X-linked optic atrophy and present two new pathogenic variants in the WDR45 gene. Methods: Case series and molecular analysis of two families of Jewish Ashkenazi descent with early onset bilateral optic atrophy. Whole-exome sequencing (WES) and bioinformatic analysis were performed, followed by Sanger sequencing and segregation analysis. Results: In both families, male siblings (three in family 1, two in family 2) had early-onset isolated bilateral optic atrophy. The sibling's healthy mother (and in the second family also one healthy sister) had a mild presentation, suggesting a carrier state and an X-linked inheritance pattern. All participants were otherwise healthy, apart from mild learning disabilities and autism spectrum disorder in two siblings of the second family. Variants in known optic atrophy genes were excluded. Analysis revealed a point variant in the WDR45 gene-a missense variant in the first family, NM_001029896.2:c.107C>A; NP_001025067.1:p.Pro36His (variant ID: 1704205), and a splice site variant in the second family, NM_001029896.2:c.236-1G>T; NP_009006.2:p.Val80Leu (variant ID: 1704204), located on Xp11.23 (OPA2 locus). Both variants are novel and predicted as pathogenic. In both families, the variant was seen with full segregation with the disease, occurring in all affected male participants and in one allele of the carrier females, as well as none of the healthy participants. Conclusions: Among two families with isolated X-linked optic atrophy, molecular analysis revealed novel variants in the WDR45 gene in full segregation with the disease. This gene resides within the OPA2 locus, previously described to associate with X-linked optic atrophy. Taken together, these findings suggest that certain pathogenic variants in the WDR45 gene are associated with isolated X-linked optic atrophy.
Güncel Retina Dergisi (Current Retina Journal) · 2022 · 0 citations · open access
Other Hereditary Syndromes Associated with Secondary Optic Atrophy
AbstractOptic neuropathy is a cause that seriously impairs vision loss, which we frequently encounter in ophthalmology practice. Although it is frequently seen with eye diseases such as glaucoma, it can also be seen together with systemic neurodegenerative syndromes. In this review, we have included some rare syndromes that cause genetically inherited optic atrophy. In these syndromes, the structure of the encoded proteins is disrupted as a result of mutated genes. The cellular disorder is reflected in the phenotype by affecting the related intracellular chemical reaction.
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.
