DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for night blindness — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNight blindness maps to a 5-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 night blindness 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
rhodopsin (RHO) — RHO 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 5W0P · 3.013 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2011 study of a consanguineous Pakistani family with congenital stationary night blindness identified a homozygous missense mutation in GNAT1, p.D129G, which segregated with the disorder in an autosomal recessive pattern. The mutation was absent in 192 ethnically matched control chromosomes. Expression analysis in mice showed Gnat1 is expressed from approximately postnatal day 7 and predominantly in the retina. The study did not test any treatment.
A 2019 study tested a combination of three FDA-approved monoaminergic drugs—metoprolol, bromocriptine, and tamsulosin—in mice lacking rod transducin (Gnat1-/-), cone transducin (Gnat2-/-), visual arrestin 1 (Arr1-/-), or rhodopsin kinase 1 (Grk1-/-). Gnat1-/- mice showed slightly increased susceptibility to rod light damage; Gnat2-/- mice were very resistant. Arr1-/- and Grk1-/- mice were sensitive for both rod and cone light damage and showed robust retinal inflammation seven days after bright light exposure. Pretreatment with the drug combination rescued the retina in all genetic backgrounds, starting at doses of 0.2 mg/kg metoprolol, 0.02 mg/kg bromocriptine, and 0.01 mg/kg tamsulosin in Gnat1-/- mice. Therapeutic doses increased in parallel with light-damage severity. The authors concluded that patients with congenital stationary night blindness and Oguchi disease may be at elevated risk of bright light toxicity, and that drug regimens stimulating Gi signaling while attenuating Gs and Gq signaling might be a disease-modifying therapy for photoreceptor degeneration.
A 1998 case report described a patient with acquired unilateral night blindness. Visual evoked potential latencies were prolonged to incremental stimulation of the affected left eye but normal for decremental stimulation of that eye and for both incremental and decremental stimulation of the right eye. A similar asymmetry was seen for saccadic eye movements. The authors interpreted this as supporting an ON-pathway dysfunction.
A 2006 abstract labelled as being about phototransduction in a transgenic mouse model of Nougaret night blindness actually contains only text from stroke management guidelines, with no data on night blindness or any treatment. A 2011 abstract titled "The first consultation" states that patients complaining of poor night vision need a full ophthalmological workup including anamnesis, visual acuity, biomicroscopy, fundus examination, visual field testing, and possibly flash ERG, and that not all such patients are truly night blind. It reports no treatment data.
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.
Journal of Neuroscience · 2006 · 23 citations · open access
Phototransduction in a Transgenic Mouse Model of Nougaret Night Blindness
AbstractThe National Clinical Guidelines for Stroke cover the management of stroke from the acute illness through to transfer of care from hospital to the community, to longer-term problems including carer support and secondary prevention. They are designed to be read by all health and social service professionals, including those working in primary care. Since the guidelines were first published there have been some major developments in stroke research. These have now been incorporated into an updated supplement to the guidelines. The new updates include: The recommendation that specialist stroke services should include a neurovascular clinic to enable patients with transient ischaemic attack (TIA) and minor stroke, (where the patient has not been admitted to hospital), to be investigated and treated within a maximum of two weeks. Changes in the recommendations about the management of blood pressure after stroke following the publication of the HOPE and PROGRESS trials. Although advances in therapy research do not warrant radical alterations to practice, two changes have been made. These recommend the use of resisted exercise to improve motor function in targeted muscles and that patients should be given as much opportunity to practice tasks as possible. More precise recommendations on the management of depression. The withdrawal of some recommendations concerning the management of shoulder pain, deep venous thromboses and biofeedback. With the research evidence evolving at a rapid rate a new version of the complete guidelines will be published in 2003.
A Mixture of U.S. Food and Drug Administration–Approved Monoaminergic Drugs Protects the Retina From Light Damage in Diverse Models of Night Blindness
AbstractPurpose: The purpose of this study was to test the extent of light damage in different models of night blindness and apply these paradigms in testing the therapeutic efficacy of combination therapy by drugs acting on the Gi, Gs, and Gq protein-coupled receptors. Methods: Acute bright light exposure was used to test susceptibility to light damage in mice lacking the following crucial phototransduction proteins: rod transducin (GNAT1), cone transducin (GNAT2), visual arrestin 1 (ARR1), and rhodopsin kinase 1 (GRK1). Mice were intraperitoneally injected with either vehicle or drug combination consisting of metoprolol (β1-receptor antagonist), bromocriptine (dopamine family-2 receptor agonist) and tamsulosin (α1-receptor antagonist) before bright light exposure. Light damage was primarily assessed with optical coherence tomography and inspection of cone population in retinal whole mounts. Retinal inflammation was assessed in a subset of experiments using autofluorescence imaging by scanning laser ophthalmoscopy and by postmortem inspection of microglia and astrocyte activity. Results: The Gnat1-/- mice showed slightly increased susceptibility to rod light damage, whereas the Gnat2-/- mice were very resistant. The Arr1-/- and Grk1-/- mice were sensitive for both rod and cone light damage and showed robust retinal inflammation 7 days after bright light exposure. Pretreatment with metoprolol + bromocriptine + tamsulosin rescued the retina in all genetic backgrounds, starting at doses of 0.2 mg/kg metoprolol, 0.02 mg/kg bromocriptine, and 0.01 mg/kg tamsulosin in the Gnat1-/- mice. The therapeutic drug doses increased in parallel with light-damage severity. Conclusions: Our results suggest that congenital stationary night blindness and Oguchi disease patients can be at an elevated risk of the toxic effects of bright light. Furthermore, systems pharmacology drug regimens that stimulate Gi signaling and attenuate Gs and Gq signaling present a promising disease-modifying therapy for photoreceptor degenerative diseases.
ON-PATHWAY DYSFUNCTION IN A PATIENT WITH ACQUIRED UNILATERAL NIGHT BLINDNESS
AbstractPURPOSE: To investigate possible functional correlates of an apparent ON-pathway defect observed in the cone electroretinogram of a patient with acquired unilateral night blindness. METHOD: Visual evoked potentials were recorded to the onset of a grid pattern consisting of either incremental or decremental squares. Saccadic eye movements were measured to luminance increments and decrements presented 5 degrees from fixation. The patient's results were compared with normative data. RESULTS: Visual evoked potential latencies were prolonged to incremental stimulation of the patient's affected left eye but were within normal limits for the other three conditions (increments and decrements, right eye; decrements, left eye). A similar pattern of asymmetry between latencies to incremental and decremental stimulation of the affected eye was observed for saccadic eye movements. CONCLUSIONS: The observed predominant delay in response to luminance increments supports the hypothesis of an ON-pathway dysfunction in this patient with acquired unilateral night blindness.
AbstractAbstract Purpose Patients with complaints of seeing badly in the dark need a full ophthalmological workup. Methods Acquired versus congenital nightblindness has to be questioned in a full anamnesis. Visual acuity, biomicroscopy and fundus examination are essential followed by visual field testing and possibly visual electrophysiology (flash ERG) Results Several causes of congenital and acquired nightblindness can be found. Not all patients complaining of seeing badly in the dark are "nightblind" Conclusion A full clinical ophthalmological work up can identify adequately several causes of night blindness
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.
