DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for retinal macular dystrophy type 2 — 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 moduleRetinal macular dystrophy type 2 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 retinal macular dystrophy type 2 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 2025 case report describes a 65-year-old man with slowly worsening central vision over several years, parafoveal pigmentary changes, and genetic testing revealing a homozygous pathogenic variant in USH2A (c.10342G>A, p. Glu3448Lys). This is the first reported case of isolated maculopathy in USH2A-associated retinal dystrophy, which usually presents with a rod-cone phenotype. The same year, a multicentre retrospective case series of 60 patients from 14 centres in 11 countries with autosomal recessive IMPG2-associated retinal dystrophy found that 77% had early-onset disease (mean age of onset 10.8 years) and 23% had late-onset disease (mean age of onset 34.3 years). Mean best-corrected visual acuity was 0.55 LogMAR at a mean age of 33 years. Forty-eight percent presented with nyctalopia, 38% with decreased visual acuity, and 88% were myopic. Foveal atrophic changes were common on OCT and fundus autofluorescence. The authors concluded that younger patients are more likely to benefit from future trials due to early macular involvement.
A 2025 report on Refsum disease identified two patients with novel pathogenic variants in PHYH who presented with retinal findings: one with retinitis pigmentosa and poor vision since childhood, the other with pigmentary changes at the macula. Both had elevated phytanic acid levels (256 µg/mL and 48.2 µmol/L; normal <3 µg/mL and <2.2 µmol/L) and systemic features including abnormal metatarsals and dry skin; one also had anosmia, kidney disease, peripheral neuropathy and hearing impairment. The authors document for the first time an association between macular dystrophy and Refsum disease, but note that improvements in vision and slowing retinal degeneration are less achievable even with dietary modification.
Two earlier review articles (2015, 2016) note that research in genetic and cellular therapy for retinal dystrophies is burgeoning, with many ongoing trials aiming to reverse or stop disease progression, and that good results have been achieved for complications such as cystoid macular oedema and choroidal neovascularisation. However, both reviews emphasise the immense complexity of these dystrophies and the challenges researchers face. No drug is named in any of these abstracts, no efficacy data for any specific treatment are reported, and no completed trial results for retinal macular dystrophy type 2 are provided. What is still missing are completed, controlled trials with sufficient sample sizes, validated endpoints for macular function, and patient stratification by genotype and age of onset.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Middle East African Journal of Ophthalmology · 2016 · 18 citations
Clinical trials in retinal dystrophies
AbstractResearch development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field - the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges.
Developments in ophthalmology · 2015 · 5 citations
Retinal Hereditary and Degenerative/Dystrophic Diseases (Non-Age-Related Macular Degeneration)
AbstractThe definition of hereditary retinal diseases includes heterogeneous conditions leading to significant visual impairment. Great strides are being made in the management of many of these dystrophies, with many ongoing trials aiming to ascertain if a pharmacological therapy can reverse or at least stop the natural course of these disorders. In addition, good results have also been achieved in the treatment of typical complications of inherited dystrophies such as cystoid macular edema and choroidal neovascularization.
An <i>USH2A</i> variant leading to isolated maculopathy: a novel phenotype
AbstractIntroduction To describe examination and findings in a case of isolated maculopathy with genetic testing revealing an USH2A genotype.Methods/Results A 65-year-old man was found to have slowly worsening central vision in both eyes over several years. Fundus examination showed parafoveal pigmentary changes with an otherwise normal peripheral exam in both eyes. Fundus autofluorescence revealed parafoveal hypofluorescence with surrounding ring like area of hyperfluorescence, with optical coherence tomography (OCT) showing retinal thinning and parafoveal photoreceptor loss. Multifocal electroretinography (ERG) demonstrated diminished central responses, with full field ERG showing normal scotopic response and reduced photopic responses. Genetic testing for retinal dystrophies revealed a homozygous pathogenic variant in USH2A c.10342G>A, p. Glu3448Lys.Discussion USH2A-associated retinal dystrophy usually presents with a rod-cone phenotype. While reports of a cone-rod phenotype have been described, we present the first reported case of isolated maculopathy in USH2A-associated retinal dystrophy.
American Journal of Ophthalmology · 2025 · 1 citations · open access
Natural History of Autosomal Recessive IMPG2-Associated Retinal Dystrophy
AbstractPURPOSE: To describe the natural history of autosomal recessive IMPG2-associated retinal dystrophy. DESIGN: Multicenter international retrospective case series. METHODS: Review of clinical notes, retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), and molecular genetic testing, of sixty patients with molecularly confirmed IMPG2-associated retinal dystrophy from 14 tertiary eye centers. Qualitative OCT and FAF imaging analysis. RESULTS: In total, 60 patients from 52 pedigrees with likely disease-causing variants in IMPG2 from 14 tertiary referral centers in 11 countries were ascertained for phenotyping. Twenty-two patients were females (36.7%). Of those with documented age of disease onset, 23% had "late onset" (>18 years old [yo]) with a mean age of onset of 34.3 yo, and 77% had "early onset" disease (<18 yo) with a mean age of onset of 10.8 yo. Mean best-corrected visual acuity (BCVA) was 0.55 LogMAR at a mean age of 33 yo. Forty-eight percent of the patients presented with nyctalopia and 38% presented with decreased BCVA. Eighty-eight percent of the patients were myopic. Foveal involvement with atrophic changes was a common finding on OCT and FAF. Fifty-three variants were identified: 13 missense (25%), 12 nonsense (23%), 11 splicing variants (21%), 16 frameshifts (30%), and one large deletion (2%). Twenty-one (40%) of the variants were not previously clinically characterized. CONCLUSION: Autosomal recessive IMPG2-retinal dystrophy is typically an early onset retinal dystrophy associated with poor visual acuity. Younger patients are more likely to benefit from intervention in future trials due to early macular involvement in most patients.
Identification of novel pathogenic variants in the <i>PHYH</i> gene and extending the phenotypic range in Refsum disease
AbstractPurpose Two patients with a suspected inherited retinal dystrophy (IRD) were referred to a specialist ophthalmology clinic for genetic testing to determine the cause of their disease.Case Report A 50-year-old female patient (P1) presented with retinitis pigmentosa and poor vision since childhood. Molecular genetic testing in P1 revealed two novel pathogenic variants in PHYH (NM_006214.4): p.(Val93*) and p.(Asn71Ilefs*23). A 57-year-old male patient (P2) presented with pigmentary changes at the macula. Molecular genetic testing in P2 revealed two novel variants in PHYN: p.(Phe183Ser) and c.2461G>C (splice acceptor). Both patients were referred to the metabolic disease clinic and phytanic acid levels were found to be 256 µg/mL in P1 (normal is < 3 µg/mL) and 48.2 µmol/L in P2 (normal is < 2.2 µmol/L) confirming the diagnosis of Refsum disease. Both patients shared systemic features of the disease including bilaterally abnormal metatarsals and dry skin, while P1 also had characteristic anosmia, kidney disease, peripheral neuropathy and mild hearing impairment.Conclusion We document for the first time an association between macular dystrophy and Refsum disease. Early diagnosis is important so that diet can be modified to improve prognosis for the complications associated with Refsum disease, although improvements in vision, slowing the retinal degeneration and overcoming refractory miosis, are less achievable.
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.
