DeCure for Leber congenital amaurosis with early-onset deafness
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Leber congenital amaurosis with early-onset deafness — 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 moduleLeber congenital amaurosis with early-onset deafness 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 leber congenital amaurosis with early-onset deafness 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
tubulin beta 4B class IVb (TUBB4B) — TUBB4B 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8SH7 · 2.8 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
Leber congenital amaurosis with early-onset deafness is an autosomal dominant condition caused by pathogenic variants in TUBB4B, characterised by early and severe loss of photoreceptor and cochlear cells, with the majority of reported cases caused by missense mutations in the R390/R391 hotspot. A 2025 report of seven individuals from three unrelated families identified a novel TUBB4B variant (c.784C>T, p.R262W) outside that canonical hotspot, associated with cone-rod dystrophy and sensorineural hearing loss that generally features a later age of onset than the Leber congenital amaurosis caused by hotspot variants. The same 2025 paper notes that this expands the mutation spectrum and phenotypic range of TUBB4B-associated retinopathies.
Earlier reports describe patients with Leber congenital amaurosis and additional neurological features. A 1984 paper described three patients (two siblings) with Leber congenital amaurosis and cerebellar disease; computed tomographic scans in two patients showed hypoplasia of the cerebellar vermis, and despite blindness and severe motor deficits all three achieved relatively normal intellectual and psychosocial milestones. A 2016 report of a four-year-old girl from a consanguineous Egyptian family with a novel homozygous deletion in RPGRIP1 (c.420delG) described severe visual impairment from infancy, fundus disc pallor and attenuated vessels, neurodevelopmental delay, and brain atrophy on CT scan. That mutation was not detected in 80 ethnically matched controls.
A 2008 case report from Kaduna, Nigeria, described Leber congenital amaurosis in three siblings and discussed genetic issues, clinical presentation, counselling, and treatment of this irreversible blinding condition. A 2009 article recounts that in 2001 a team led by Jean Bennett restored vision to three dogs with Leber congenital amaurosis using gene transfer, a report that electrified families with the disease and generated hundreds of inquiries from expectant parents.
What is still missing are controlled human trials of any intervention for Leber congenital amaurosis with early-onset deafness specifically, adequate funding for natural history studies that stratify patients by genotype (including the newly described TUBB4B p.R262W variant), and trial designs that account for the phenotypic variability between hotspot and non-hotspot mutations.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 1984 · 24 citations
Leber's Congenital Amaurosis
AbstractThree patients (two of them siblings) had Leber's congenital amaurosis and cerebellar disease. Despite blindness and severe motor deficits, all three patients have achieved relatively normal intellectual and psychosocial milestones. Computed tomographic scans, performed in two patients, demonstrated hypoplasia of the cerebellar vermis in both. The presence of delayed speech and motor development as well as structural CNS abnormalities in children with Leber's congenital amaurosis does not necessarily imply that severe intellectual impairment will be present.
Klinische Monatsblätter für Augenheilkunde · 2016 · 7 citations · open access
A Novel Recessive RPGRIP1 Mutation Causing Leber Congenital Amaurosis
AbstractBACKGROUND: Leber congenital amaurosis is an early-onset childhood severe retinal dystrophy, of significant genetic heterogeneity. RPGRIP1 is ubiquitously expressed, but mutations in RPGRIP1 lead to a retina-restricted phenotype, such as Leber congenital amaurosis and cone-rod dystrophy. PATIENT AND METHODS: We analysed a consanguineous family from Egypt in which one individual, a four-year-old girl, was affected with Leber congenital amaurosis. IROme, a proprietary enrichment system for retinal dystrophy genes, was applied and high throughput sequencing was performed. RESULTS: Severe visual impairment was reported during infancy. The fundus of the affected patient exhibited disc pallor and attenuated vessels. Neurodevelopmental delay and brain atrophy in the CT scan were reported. Genomic sequencing identified a novel homozygous deletion, c.[420delG], in RPGRIP1. This mutation was not detected in 80 ethnically matched controls and has not been reported elsewhere. CONCLUSIONS: Identifying new mutations in Leber congenital amaurosis-related genes and their clinical manifestations can improve our understanding of the disease and could help to stratify the population for potential therapies.
Nigerian Journal of Ophthalmology · 2008 · 1 citations · open access
Lebers Amaurosis in Three Siblings: A case report
AbstractThis case report appears to be first reported incident of Lebers congenital amaurosis in three siblings in Kaduna State. Genetic issues, clinical presentation, counselling, treatment and future progression of this irreversible blinding condition are discussed. Keywords: Lebers amaurosis, retinitis pigmentosa, Kaduna, NigeriaNigerian Journal of Ophthalmology Vol. 16 (1) 2008: pp. 26-29
Cambridge University Press eBooks · 2009 · 0 citations
Great Expectations and Hard Times: expectation management in gene transfer
AbstractIn 2001, a report in Nature Genetics raised the possibility that a rare, hereditary form of blindness, Leber's congenital amaurosis (LCA), might soon have a cure. A team of researchers led by Jean Bennett of the University of Pennsylvania's Scheie Eye Institute had successfully restored vision to three dogs with LCA. According to news stories, the report “electrified” families with the disease; said one mother of an LCA child, “we are bursting at the seams.” Word spread like “wildfire,” according to Bennett, who received hundreds of inquiries from expectant parents.
A novel missense <i>TUBB4B</i> variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss
AbstractPathogenic variants in TUBB4B, which encodes the β-tubulin 4B isotype of microtubule subunits, have been associated with Leber congenital amaurosis with early-onset deafness (LCAEOD), an autosomal dominant condition characterized by early and severe loss of photoreceptor and cochlear cells. The majority of reported cases feature early disease onset and are caused by missense mutations in the R390/R391 hotspot. Multimodal evaluation included ultra-widefield pseudocolor and autofluorescence fundus photography, spectral-domain optical coherence tomography, full-field electroretinography, Goldmann kinetic perimetry, audiography, and genetic testing with next-generation sequencing. We report seven individuals from three unrelated families affected by cone-rod dystrophy and sensorineural hearing loss associated with a novel variant in TUBB4B (c.784C > T, p.R262W). Cone-rod dystrophy associated with this variant generally features a later age of onset compared to the Leber congenital amaurosis caused by variants in the canonical hotspot. This report expands the mutation spectrum and phenotypic range of TUBB4B-associated retinopathies beyond the R390/R391 hotspot and may offer insight into the pathogenesis of this rare tubulinopathy.
A novel missense <i>TUBB4B</i> variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss
AbstractPathogenic variants in TUBB4B, which encodes the β-tubulin 4B isotype of microtubule subunits, have been associated with Leber congenital amaurosis with early-onset deafness (LCAEOD), an autosomal dominant condition characterized by early and severe loss of photoreceptor and cochlear cells. The majority of reported cases feature early disease onset and are caused by missense mutations in the R390/R391 hotspot. Multimodal evaluation included ultra-widefield pseudocolor and autofluorescence fundus photography, spectral-domain optical coherence tomography, full-field electroretinography, Goldmann kinetic perimetry, audiography, and genetic testing with next-generation sequencing. We report seven individuals from three unrelated families affected by cone-rod dystrophy and sensorineural hearing loss associated with a novel variant in TUBB4B (c.784C > T, p.R262W). Cone-rod dystrophy associated with this variant generally features a later age of onset compared to the Leber congenital amaurosis caused by variants in the canonical hotspot. This report expands the mutation spectrum and phenotypic range of TUBB4B-associated retinopathies beyond the R390/R391 hotspot and may offer insight into the pathogenesis of this rare tubulinopathy.
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.
