DeCure for Autosomal dominant optic atrophy plus syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant optic atrophy plus syndrome — 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 moduleAutosomal dominant optic atrophy plus syndrome 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 autosomal dominant optic atrophy plus syndrome 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
A 2019 review notes that up to 20% of patients with autosomal dominant optic atrophy develop additional deficits including sensorineural hearing loss, ataxia, myopathy, peripheral neuropathy, spastic paraparesis, and chronic progressive external ophthalmoplegia. A 2013 review describes these as "plus" symptoms that may follow decades after vision loss and stresses that clinicians should recognise the potential link. The condition is inherited as an autosomal dominant trait with high penetrance, and the responsible gene was mapped to chromosome 3q27-3q28 in 1994, with later refinement to a 4 to 7 centimorgan region.
A 1985 paper reviewing three affected members of one family (a father and two daughters) and comparing them with 17 additional cases argues that patients with early or congenital onset are at the more severe end of a distribution curve. The less severely affected patients were older and often had passed many years with little or no visual difficulties. The paper suggests there is probably only one genetic locus for autosomal dominant optic atrophy, with variation being a recognised feature of autosomal dominant inheritance.
A 2010 report describes a single family with 20 affected members across three generations who had optic atrophy without any other ocular or extraocular manifestations. In that family, severity was bimodal: 4 male patients complained of severe impairment of vision since childhood, while 16 other subjects (7 males and 9 females) were completely asymptomatic. The authors propose this could be a variety of autosomal dominant optic atrophy characterised by sex-influenced severity.
No clinical trial data for any drug treatment of autosomal dominant optic atrophy plus syndrome appear in these abstracts. What is missing is any funded trial designed to test a repurposed drug in a defined patient population, with stratification by genetic subtype, age of onset, or presence of plus symptoms.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Seminars in Ophthalmology · 2013 · 33 citations
Autosomal Dominant Hereditary Optic Neuropathy (ADOA): A Review of the Genetics and Clinical Manifestations of ADOA and ADOA+
AbstractAutosomal dominant hereditary optic atrophy (ADOA), also known as Kjer's syndrome, is a common hereditary cause of progressive bilateral vision loss. Recent advancements in the understanding of the genetics of this condition have revealed that a single gene may account for a large portion of the clinical manifestations in these patients. It has long been recognized that in a not-insignificant number of ADOA patients, a number of "plus" symptoms may follow decades after vision loss. It is important that clinicians recognize the potential link to "plus" manifestations. The goal of this manuscript is to provide for the general ophthalmologist a practical outline of the genetics and clinical manifestations of ADOA and the ADOA+.
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.
Ophthalmic Paediatrics and Genetics · 1985 · 4 citations
Variable severity in autosomal dominant optic atrophy
AbstractThere are some indications in the literature on autosomal dominant optic atrophy that there are two genetic types - a congenital and a post-natal. This paper reviews the ocular findings of three affected members of a family with autosomal dominant optic atrophy - a father and two daughters - which appear to fit the criteria for a 'congenital' type of optic atrophy. Comparison with an additional 17 cases indicates that those with an early or congenital onset are at the more severe end of a distribution curve of involvement. The less severely affected patients were older and often had passed many years with little or no visual difficulties. Such variation is a recognized feature of autosomal dominant inheritance and is the basis for suggesting that there is probably only one genetic locus for autosomal dominant optic atrophy.
AbstractKjer DOMINANToptic atrophy (DOA) is a rare primary degeneration of the retinal ganglion cell. In this issue of theArchives, 2 articles describing the genetic analysis of single, large, affected families confirm the initial genomic mapping of this disease to chromosome 3q27-3q28 and refine the localization of the gene to a 4 to 7 centimorgan region.<sup>1,2</sup>These mapping studies are important steps toward the cloning and characterization of the actual gene. Although this disorder is a rare cause of blindness, the genetic analysis of this disease will provide an opportunity to investigate one mechanism of optic nerve degeneration and to determine what role this gene may play in other degenerative disorders of the retinal ganglion cell and optic nerve. See also pages 95 and 100 Kjer DOA is inherited as an autosomal dominant trait with high penetrance. The responsible gene was initially mapped to chromosome 3q27-3q28 in 1994.
AbstractThere is a broad differential diagnosis for bilateral optic neuropathies, including inflammatory, ischemic, compressive, traumatic, nutritional, toxic, and inherited causes. In this chapter, we begin by discussing the approach to the patient who has bilateral symmetric optic neuropathies. We next review the genetic basis, clinical features, and natural history of autosomal dominant optic atrophy. We list other deficits that can occur in up to 20% of patients with this condition, which can include sensorineural hearing loss, ataxia, myopathy, peripheral neuropathy, spastic paraparesis, and chronic progressive external ophthalmoplegia. Lastly, we discuss the evaluation and management approach for autosomal dominant 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.
