DeCure for Congenital hypotrichosis with juvenile macular dystrophy
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital hypotrichosis with juvenile 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 moduleCongenital hypotrichosis with juvenile 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 congenital hypotrichosis with juvenile 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
cadherin 3 (CDH3) — CDH3 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 4ZMN · 2.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Two siblings aged 25 and 23 years were described in 1995 with an association of juvenile macular dystrophy and congenital hypotrichosis, proposed as an autosomal recessive condition. A 6-year-old boy reported in 2015 presented with decreased visual acuity, light sensitivity, and bull’s eye maculopathy bilaterally; fundus autofluorescence showed severe hypoautofluorescence with retinal pigment epithelium loss, and spectral domain optical coherence tomography showed disruption of retinal pigment epithelium, photoreceptors, and inner/outer segments. He had a cadherin-3 genetic defect. An 11-year-old Portuguese girl born to related parents had hypotrichosis since birth and macular dystrophy diagnosed at age 5, with macular pigmentary abnormalities on fundus examination and fluorescein angiography; no molecular analysis was done. A 2020 report from Saudi Arabia described a family member with alopecia since birth and severe early visual impairment, with diagnosis confirmed by genetic testing for CDH3 mutation. A 2024 series of three cases of hereditary juvenile macular dystrophy (HJMD) noted that the same CDH3 mutation also causes ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS), which includes macular dystrophy, hypotrichosis, dysplastic nails, partial anodontia, and limb defects.
The disease is consistently linked to mutations in the CDH3 gene encoding P-cadherin, expressed in retinal pigment epithelium and hair follicles. The 2015 case report noted that a workup for Stargardt disease was negative, and that hypotrichosis with juvenile macular dystrophy should be in the differential for macular degeneration during the first four decades of life. The 2016 Portuguese case emphasised that fundus examination should be considered mandatory in the assessment of congenital hypotrichosis. The 2020 report stressed the importance of genetic testing for proper genetic counselling. No treatment or intervention is mentioned in any of these abstracts.
What is still missing is any clinical trial data, any drug or gene therapy tested in these patients, and any systematic study of disease progression or genotype-phenotype correlation beyond single case reports. There is no evidence on whether early detection alters visual outcome, and no large cohort with longitudinal follow-up. Funding for natural history studies and for preclinical development of CDH3-directed therapies is absent. Patient stratification by specific CDH3 mutation type has not been attempted.
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 · 1995 · 32 citations
Unusual association of juvenile macular dystrophy with congenital hypotrichosis: occurrence in two siblings suggesting autosomal recessive inheritance
AbstractA familial association between juvenile macular dystrophy and congenital hypotrichosis is described in two siblings aged 25 and 23 years. We put forward arguments for locating the retinal alteration at the level of the retinal pigment epithelium and suggest that the hair disorder could be a Marie-Unna type hypotrichosis. This association is transmitted as an autosomal recessive condition.
A CASE OF HYPOTRICHOSIS WITH JUVENILE MACULAR DYSTROPHY
AbstractIn Brief Purpose: To report a very rare case of hypotrichosis with juvenile macular dystrophy. Methods: Clinical case report and literature review. Results: A 6-year-old boy was referred to us for a retinal evaluation after retinal defects were found bilaterally by his optometrist. His ocular symptoms included decreased visual acuity and light sensitivity. His ocular history was unremarkable. Review of systems was positive for hypotrichosis. Fundus examination revealed bull's eye maculopathy bilaterally. The patient was found to have a cadherin-3 genetic defect, which is associated with hypotrichosis with juvenile macular dystrophy. In follow-up, fundus autofluorescence revealed severe hypoautofluorescence with severe retinal pigment epithelium loss, and spectral domain optical coherence tomography showed evidence of retinal pigment epithelium, photoreceptor, and inner segment/outer segment disruption bilaterally. Conclusion: Hypotrichosis with juvenile macular dystrophy is a very rare genetic disorder that should be in the differential for macular degeneration during the first 4 decades of life. A detailed review of systems should always be performed on these patients. A case report of a 6-year-old boy who developed bull's eye maculopathy bilaterally. A workup for Stargardt disease was negative. Review of systems was positive for poor hair growth. Mutation in the cadherin-3 protein was found, which is linked to hypotrichosis with juvenile macular dystrophy.
Hypotrichosis with juvenile macular dystrophy: Portuguese case
AbstractHypotrichosis with juvenile macular dystrophy is a rare congenital disease mainly found in the Druze population of Northern Israel. This disorder is caused by the CDH3 mutation encoding P-cadherin, which is expressed in retinal pigment epithelium and hair follicles. An 11-year-old girl who was born to related Portuguese parents, had hypotrichosis since birth and macular dystrophy diagnosed at age 5. Fundus examination and fluorescein angiography revealed located macular pigmentary abnormalities. No molecular analysis was done. A fundus examination should be considered mandatory in the assessment of congenital hypotrichosis.
Hypotrichosis with Juvenile Macular Dystrophy in Saudi Arabia: A Case Report
AbstractHypotrichosis with juvenile macular dystrophy is an autosomal recessive disorder due to a mutation in the CDH3 gene. As its name indicates, the disease classically presented with hypotrichosis and early visual impairment. We describe herein a family member with alopecia since birth associated with severe visual impairment in their early life. We suspect the diagnosis of hypotrichosis with juvenile macular dystrophy. Genetic testing confirms the clinical suspension. We emphasize the importance of genetic testing for proper genetic counseling.
Indian Journal of Ophthalmology - Case Reports · 2024 · 0 citations · open access
Hereditary juvenile macular dystrophy: A series of three cases
AbstractHereditary juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder caused by mutations in the CDH3 gene. The “ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome” (EEMS) is caused by the CDH3 mutation and is characterized by macular dystrophy, hypotrichosis, dysplastic nails, partial anodontia, and various limb defects. We present a series of three cases with HJMD. The important clinical features, ocular and systemic, and genetic tests performed are highlighted in our case series.
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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