DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for occult macular dystrophy — 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 moduleOccult macular dystrophy 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 occult macular dystrophy 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
calpain 5 (CAPN5) — CAPN5 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 6P3Q · 2.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Occult macular dystrophy is defined by a slowly progressive bilateral reduction of visual acuity in patients who have a normal fundus appearance and normal fluorescein angiography, as described in a 2023 literature review that also reports a single case of a 36-year-old male diagnosed after extensive multimodal imaging, electrophysiology, and systemic screening. The condition is primarily caused by variants in the RP1L1 gene. A 2024 study of seven Chinese occult macular dystrophy patients found that five of the seven carried the RP1L1 variant c.133 C > T; p.R45W, which was associated with central vision loss and specific patterns on spectral domain optical coherence tomography and multifocal electroretinograms. Two other patients had different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C) and presented milder phenotypes. Most patients showed decreased mfERG responses in the central rings and photoreceptor layer changes on SD-OCT.
The same 2024 study also identified a rare case of vitelliform macular dystrophy linked to an RP1L1 variant, distinct from typical occult macular dystrophy presentations. This expands the spectrum of RP1L1-associated macular dystrophies. Other genetic causes can produce similar phenotypes. A 2023 report of four patients with Stargardt-like phenotypes found that their macular atrophy and pigmentary changes were associated with variants in RIMS1, CRX, CRB1, and RDH12, rather than the classic ABCA4 gene. A 2022 case described a 57-year-old woman with bilateral central macular dystrophy and compound heterozygous mutations in MFSD8 (c.154G>A, p.Gly52Arg and c.1006G>C, p.Glu336Gln), with best corrected visual acuity of 20/250 in the right eye and 20/50 in the left, stable over one year of follow-up. Her full-field electroretinography was normal but electro-oculography showed an abnormal Arden ratio in both eyes.
A 2006 study of a Swedish family with Best vitelliform macular dystrophy found that two individuals with compound heterozygous mutations in VMD2 (Arg141His and Tyr29stop) had a severe form with abnormal EOG, full-field ERG showing widespread degeneration and prolonged implicit time in the cone 30-Hz flicker, and OCT demonstrating intraretinal fluid, swelling, and thickening of the outer retina-RPE-choroid complex. A 1984 description of fenestrated sheen macular dystrophy, an autosomal dominant disorder, reported five patients across two generations with a golden sheen and tiny red fenestrations in the central macula but only mild functional disturbance even in later stages.
What is still missing are large, prospective natural history studies that stratify patients by specific RP1L1 and other gene variants, and clinical trials that test any intervention. The rarity of each genetic subtype makes recruitment slow and expensive. No therapy has been shown to alter the course of occult macular dystrophy in a controlled trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Ophthalmic Genetics · 2006 · 79 citations
Variant Phenotype of Best Vitelliform Macular Dystrophy Associated with Compound Heterozygous Mutations in<i>VMD2</i>
AbstractPURPOSE: To characterize the phenotype of members of a Swedish family with Best macular dystrophy and two distinct mutations in VMD2. METHODS: Venous blood samples were obtained from six family members and screened for mutations in VMD2. Six individuals were examined clinically, four of whom were further investigated with full-field electroretinography (ERG), electro-oculography (EOG), multifocal electroretinography (mfERG), and optical coherence tomography (OCT). RESULTS: The VMD2 mutations resulting in Arg141His and Tyr29stop were identified in family members. Two individuals harbored both mutations, one mutation in each VMD2 allele. These two family members had an abnormal EOG and their full-field ERG demonstrated widespread degeneration with a prolonged implicit time in the cone 30-Hz flicker ERG. MfERG verified reduction of the central retinal function and OCT demonstrated intraretinal fluid, swelling, and thickening of the outer retina-RPE-choroid complex (ORCC). CONCLUSION: A previously undescribed severe form of Best macular dystrophy is associated with compound heterozygous mutations in VMD2.
AbstractBackground MFSD8 mutations can cause type 7 neuronal ceroid lipofuscinosis, a systemic disorder that includes vision loss; however, such mutations can also cause isolated retinal dystrophy with vision loss without systemic signs or symptoms as first identified in 2015. This report details a previously unreported combination of compound heterozygous variants in the MFSD8 gene causing a non-syndromic, bilateral central macular dystrophy presenting in adulthood.Materials and Methods We present a case of MFSD8-associated retinal dystrophy with multimodal imaging and a review of relevant literature.Results A 57-year-old female presented for subacute, unilateral blurriness in her right eye. Best corrected visual acuity was 20/250 and 20/50 in the right and left eyes, respectively. Fundus examination and multimodal imaging revealed blunted foveal reflexes and optical gap with subfoveal ellipsoid zone loss in both eyes, right greater than left. Full field electroretinography results were within normal limits while the Arden ratio on electro-oculography was abnormal in both eyes, right more so than left. Genetic testing revealed apparently causative compound heterozygous mutations in the MFSD8 gene: c.154G>A, p.(Gly52Arg) and c.1006G>C, p.(Gluc336Gln). Visual acuity over one year of follow-up has remained stable.Conclusions To authors’ knowledge, this report is first description of this combination of mutations in the MFSD8 gene leading to non-syndromic adult-onset macular dystrophy.
AbstractFenestrated sheen macular dystrophy is an autosomal dominant macular disorder characterized by the presence in the central macular zone of a golden sheen with tiny red fenestrations. Even in the later stages, only a mild functional disturbance has been observed. There were five patients manifesting this dystrophy in two generations of a family. They represent the third family so described.
BMC Ophthalmology · 2024 · 4 citations · open access
Varied clinical presentations of RP1L1 variants in Chinese patients: a study of occult macular dystrophy and vitelliform macular dystrophy
AbstractBACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1. METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis. RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations. CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.
Arquivos Brasileiros de Oftalmologia · 2023 · 2 citations · open access
Macular dystrophies associated with Stargardt-like phenotypes
AbstractPURPOSE: Stargardt-like phenotype has been described as associated with pathogenic variants besides the ABCA4 gene. This study aimed to describe four cases with retinal appearance of Stargardt disease phenotypes and unexpected molecular findings. METHODS: This report reviewed medical records of four patients with macular dystrophy and clinical features of Stargardt disease. Ophthalmic examination, fundus imaging, and next-generation sequencing were performed to evaluate pathogenic variants related to the phenotypes. RESULTS: Patients presented macular atrophy and pigmentary changes suggesting Stargardt disease. The phenotypes of the two patients were associated with autosomal dominant inheritance pattern genes (RIMS1 and CRX) and in the other two patients were associated with recessive dominant inheritance pattern genes (CRB1 and RDH12) with variants predicted to be pathogenic. CONCLUSION: Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones.
AbstractABSTRACT Occult macular dystrophy is characterized by a slowly progressive bilateral reduction of visual acuity in patients with normal fundus and fluorescein angiography. We describe a case of a 36-year-old male patient diagnosed with this condition, after extensive investigation with multimodal imaging, electrophysiology tests, and systemic screening.
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.
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