DeCure for Congenital stationary night blindness 1H
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital stationary night blindness 1H — 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 moduleCongenital stationary night blindness 1H 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 congenital stationary night blindness 1h 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
G protein subunit beta 3 (GNB3) — GNB3 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 25ST · 3.0 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A consanguineous Pakistani family with multiple individuals showing early-onset stationary night blindness and no extraocular anomalies was studied. A genome-wide scan localised the critical interval to chromosome 3p22.1-p14.3 with a maximum two-point LOD score of 3.09 at θ = 0. A homozygous missense mutation in GNAT1, p.D129G, was identified, segregating with the autosomal recessive form of the disease and absent in 192 ethnically matched control chromosomes. Gnat1 expression was detected at approximately postnatal day 7 and was predominantly retinal.
In X-linked congenital stationary night blindness, seven of eight patients presented with decreased acuity and nystagmus without complaints of night blindness; diagnosis required electroretinogram and dark adaptation testing. Two patients showed pupillary constriction to darkness, a sign of retinal disease in young patients. A 1989 letter noted that in one X-linked pedigree, three of five affected patients showed the incomplete type of CSNB, while one patient (case IV-2) had findings more consistent with the complete type — a nonrecordable rod b-wave, absent oscillatory potentials, and high myopia — leading the authors to suggest the incomplete type might be a variation of the complete type.
Incomplete CSNB is a rare subtype with only around 30 detailed clinical case descriptions (excluding female carriers) published by 2024. First symptoms — nyctalopia, nystagmus, strabismus, and markedly reduced visual acuity — typically appear within the first year of life, with nystagmus usually the first observable symptom.
No drug treatment is mentioned in any of these abstracts. What is missing for any therapeutic approach is a molecular understanding of how specific GNAT1 mutations disrupt rod phototransduction, a suitable animal model for preclinical testing, and any clinical trial infrastructure for a disease with such a small, genetically heterogeneous patient population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
<i>GNAT1</i>Associated with Autosomal Recessive Congenital Stationary Night Blindness
AbstractPURPOSE: Congenital stationary night blindness is a nonprogressive retinal disorder manifesting as impaired night vision and is generally associated with other ocular symptoms, such as nystagmus, myopia, and strabismus. This study was conducted to further investigate the genetic basis of CSNB in a consanguineous Pakistani family. METHODS: A consanguineous family with multiple individuals manifesting cardinal symptoms of congenital stationary night blindness was ascertained. All family members underwent detailed ophthalmic examination, including fundus photographic examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion and genome-wide linkage analyses were completed and two-point LOD scores were calculated. Bidirectional sequencing of GNAT1 was completed, and quantitative expression of Gnat1 transcript levels were investigated in ocular tissues at different postnatal intervals. RESULTS: The results of ophthalmic examinations were suggestive of early-onset stationary night blindness with no extraocular anomalies. The genome-wide scan localized the critical interval to chromosome 3, region p22.1-p14.3, with maximum two-point LOD scores of 3.09 at θ = 0, flanked by markers D3S3522 and D3S1289. Subsequently, a missense mutation in GNAT1, p.D129G, was identified, which segregated within the family, consistent with an autosomal recessive mode of inheritance, and was not present in 192 ethnically matched control chromosomes. Expression analysis suggested that Gnat1 is expressed at approximately postnatal day (P)7 and is predominantly expressed in the retina. CONCLUSIONS: These data suggest that a homozygous missense mutation in GNAT1 is associated with autosomal recessive stationary night blindness.
British Journal of Ophthalmology · 1985 · 42 citations · open access
Pupillary constriction to darkness.
AbstractPatients with congenital achromatopsia and congenital stationary night blindness have been known to show a transient pupillary constriction to darkness. We examined 50 normal subjects and 108 patients with retinal and optic nerve dysfunction to see if any had an initial pupillary constriction to darkness. We used a new infrared television apparatus. Four patients with congenital stationary night blindness, four with achromatopsia, two with bilateral optic neuritis, and one with dominant optic atrophy showed the phenomenon. In the patients who showed this unusual pupillary response to darkness it was the first observable event every time the lights were turned off. The constriction could usually be seen with a handlight, and it was similar in latency to the normal pupillary dilatation to darkness. Pupillary constriction to darkness is a clinically valuable sign that can be used in the detection of congenital retinal disease in children with poor vision.
Congenital Stationary Night Blindness Presenting as Leber's Congenital Amaurosis
AbstractTwo siblings with autosomal-recessive congenital stationary night blindness were clinically blind in infancy. Both had markedly abnormal electroretinograms that, in the first child, led consultants at two university centers to make the diagnosis of Leber's congenital amaurosis. The patients had intermittent nystagmus and esotropia, but good photopic vision developed eventually. Scotopic vision was clearly defective in each child. Refractive error in both patients was close to emetropic in early infancy but became myopic by 1 year of age. Congenital stationary night blindness must be considered in the differential diagnosis of the blind infant.
X-Linked Congenital Stationary Night Blindness With Myopia and Nystagmus Without Clinical Complaints of Nyctalopia
AbstractSeven of eight patients presented initially or were followed for decreased acuity and nystagmus without complaints of night blindness. The diagnosis of congenital stationary night blindness was established with electroretinogram and dark adaptation testing. Careful electrodiagnostic testing is needed to provide accurate genetic counseling. Two patients showed pupillary constriction to darkness which is a sign of retinal disease in young patients.
Abstract<h3>To the Editor.</h3> —I read with interest the report by Khouri et al<sup>1</sup>on X-linked congenital stationary night blindness that was published in the October 1988Archives. It is interesting that the incomplete type of congenital stationary night blindness, which we have reported previously,<sup>2</sup>was also found in the United States. The authors noted that three of the five affected patients in their study pedigree showed ocular findings of the incomplete type. However, in one patient (case IV-2) findings were more consistent with the complete type of congenital stationary night blindness. This result led to the assumption by Khouri et al that the incomplete type may be a variation of the complete type. In case IV-2, the diagnostic basis for the complete type of congenital stationary night blindness was, acccording to Khouri et al, a nonrecordable rod b-wave, absent oscillatory potentials, and high myopia. However, judging from the
Klinische Monatsblätter für Augenheilkunde · 2024 · 0 citations
Diagnosis of Incomplete Congenital Stationary Night Blindness in a 2-year-old boy
AbstractCongenital stationary night blindness (CSNB) is an umbrella term for a clinically and genetically heterogeneous group of rare inherited retinal diseases (IRDs). Incomplete CSNB (iCSNB) is a rare subtype, with only around 30 detailed clinical case descriptions (excluding reports on female carriers) published so far [1], [2], [3], [4], [5]. First symptoms such as nyctalopia, nystagmus, strabismus and markedly reduced visual acuity (VA) typically occur within the first year of life, with nystagmus usually being the first observable symptom [6].
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.
