DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for patterned macular dystrophy — 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 modulePatterned macular dystrophy 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 patterned 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
MAPK activated protein kinase 3 (MAPKAPK3) — MAPKAPK3 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 2-quinolin-3-ylpyridin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3FHR · 1.9 Å · ligand 2-(2-QUINOLIN-3-YLPYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE (P4O). Experimental structure, not a prediction.
What the evidence adds up to
In a 2006 study of a Swedish family with Best vitelliform macular dystrophy, two individuals who carried both the Arg141His and Tyr29stop mutations in VMD2 (one mutation in each allele) had an abnormal electro-oculogram and full-field electroretinography showing widespread degeneration with a prolonged implicit time in the cone 30-Hz flicker response. Multifocal ERG confirmed reduced central retinal function, and optical coherence tomography showed intraretinal fluid, swelling, and thickening of the outer retina-RPE-choroid complex. The authors described this as a previously unreported severe form of Best macular dystrophy associated with compound heterozygous VMD2 mutations.
A 2022 case report described a 57-year-old woman with asymmetric adult-onset macular dystrophy who carried compound heterozygous mutations in MFSD8 (c.154G>A, p.Gly52Arg and c.1006G>C, p.Glu336Gln). Best corrected visual acuity was 20/250 in the right eye and 20/50 in the left. Full-field ERG was within normal limits, but the Arden ratio on electro-oculography was abnormal in both eyes, worse on the right. Over one year of follow-up, visual acuity remained stable. The authors noted that MFSD8 mutations can cause isolated retinal dystrophy without systemic signs, as first reported in 2015.
A 2023 case series of four patients with macular dystrophy and clinical features of Stargardt disease found that two patients had variants in autosomal dominant genes (RIMS1 and CRX) and two had variants in recessive genes (CRB1 and RDH12). All four had macular atrophy and pigmentary changes. The authors concluded that macular dystrophies can show phenotypic similarity to Stargardt disease but be associated with genes other than ABCA4.
A 1993 report on two brothers with butterfly-shaped macular dystrophy documented progressive photoreceptor dysfunction over seven years, supported by ERG abnormalities, in 11 family members. The authors emphasised that butterfly-shaped macular dystrophy can be a chronic progressive disorder with secondary photoreceptor involvement.
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.
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.
Ophthalmic Paediatrics and Genetics · 1993 · 1 citations
Butterfly-shaped macular dystrophy
AbstractTwo brothers with butterfly-shaped macular dystrophy (BSMD) are reported. The anatomical and functional data were analyzed in 11 family members. Progressive photoreceptor dysfunction, supported by ERG abnormalities, was documented in both patients. The progression of the disease was observed over a period of seven years. The present observations emphasize that BSMD, at least in some cases, can be a chronic progressive disorder with secondary involvement of the photoreceptors.
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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