DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Doyne honeycomb retinal dystrophy — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDoyne honeycomb retinal dystrophy maps to a 3-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 doyne honeycomb retinal 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
peripherin 2 (PRPH2) — PRPH2 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 7ZW1 · 3.7 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
No established therapy exists for Doyne honeycomb retinal dystrophy (DHRD), a genetic disease caused by pathogenic variants of the EFEMP1 gene. A 2023 case series followed three DHRD patients (age range 41–46, all with the c.1033C>T; p.R345W variant) for up to 30 months after nanosecond 2RT laser treatment. Visual acuity improved in both eyes of case 1 and the left eye of case 2, but decreased in the right eye of case 2 and the left eye of case 3. Perimetric sensitivity was stable in case 1 and improved in both eyes of cases 2 and 3. Electroretinogram amplitude improved in cases 1 and 2 and was stable in case 3. OCT showed stable central macular thickness and retinal structure in all three patients. No treatment-related side effects were reported. The authors conclude that 2RT treatment may improve or stabilise some retinal function parameters without significant structural changes, but this is a single small case series with no control group.
A 2024 case report describes a 63-year-old male with metamorphopsia in the right eye for six months. Visual acuity was 6/6 in both eyes. Fundus examination showed multiple drusen deposits in the macula and optic nerve head with hyperpigmentation. OCT showed hyperreflective bumpy retinal pigment epithelium in Bruch’s membrane. Fundus autofluorescence showed hyperfluorescence in areas of drusen. Fluorescein angiography of the right eye showed hyperfluorescence with central hypofluorescence; the left eye showed areas of blocked hypofluorescence within hyperfluorescence. This report provides no treatment data.
Broader research on retinal dystrophies is at an early stage. A 2016 review notes that progress has revealed immense complexity and challenges, with no established therapy. A 2013 review of retinitis pigmentosa states that no therapy is established, though gene therapy, pharmacological agents, neuroprotection, electrical stimulation, retinal implants, cell transplantation, and optogenetic approaches are under investigation. A 2024 study describes a porcine retina explant model that can be kept in culture for up to 28 days with good morphological preservation, intended as an intermediate model for testing future therapeutic approaches for inherited retinal dystrophies.
What is still missing for DHRD specifically: larger controlled trials with longer follow-up, validated patient stratification by genetic variant and disease stage, and dedicated funding to move beyond single case reports and small case series.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Middle East African Journal of Ophthalmology · 2016 · 18 citations
Clinical trials in retinal dystrophies
AbstractResearch development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field - the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges.
Long-Term Porcine Retina Explants as an Alternative to In Vivo Experimentation
AbstractPurpose: The porcine retina represents an optimal model system to study treatment approaches for inherited retinal dystrophies owing to close anatomical similarities to the human retina, including a cone enriched visual streak. The aim of this work was to establish a protocol to keep explants in culture for up to 28 days with good morphological preservation. Methods: Two to four retina explants per eye were obtained from the central part of the retina and transferred onto a membrane insert with the photoreceptors facing down. Different medium compositions using Neurobasal-A medium containing 100 or 450 mg/dL glucose and combinations of fetal calf serum, B-27 with or without insulin and N-2 were tested. We developed a tissue quality score with robust markers for different retinal cell types (protein kinase C alpha, peanut agglutinin and 4',6-diamidino-2-phenylindol). Results: Retinae were kept until 28 days with only little degradation. The best results were attained using Neurobasal-A medium containing 100 mg/dL glucose supplemented with B-27 containing insulin and N-2. For an easy preparation process, it is necessary to minimize transport time and keep the eyes on ice until dissected. Heat-mediated decontamination by the butcher has to be avoided. Conclusions: Using a standardized protocol, porcine retina explants represent an easy to handle intermediate model between in vitro and in vivo experimentation. This model system is robustly reproducible and contributes to the implementation of the 3R principle to minimize animal experimentation. Translational Relevance: This model can be used to test future therapeutic approaches for inherited retinal dystrophies.
Klinische Monatsblätter für Augenheilkunde · 2013 · 1 citations
Therapeutische Ansätze bei Patienten mit Retinitis pigmentosa
Abstract<b>Hintergrund:</b> Retinitis pigmentosa (RP) bezeichnet einen genetisch und klinisch heterogenen Formenkreis an dystrophischen Netzhauterkrankungen. Im Verlauf der Erkrankung kommt es zu zunehmenden Gesichtsfeldeinschränkungen bis hin zur Erblindung. Bisher ist keine Therapie etabliert. Durch zunehmendes Wissen über die zugrunde liegenden genetischen und pathophysiologischen Veränderungen gibt es eine Reihe von neuen Therapieansätzen, von denen einige hier vorgestellt werden sollen. <b>Methodik:</b> Es wurde eine systematische Literaturrecherche in PubMed zu definierten Stichworten durchgeführt. <b>Ergebnisse:</b> Zu den neuen Therapieansätzen gehören Gentherapie, pharmakologische Substanzen, Neuroprotektion, Elektrostimulation, retinale Implantate, Zelltransplantation und optogenetische Ansätze. <b>Schlussfolgerung:</b> In den letzten Jahren gab es einige Fortschritte in der Erforschung möglicher Therapieansätze bei dystrophischen Netzhauterkrankungen. Die Forschung ist in den einzelnen Bereichen unterschiedlich weit fortgeschritten. Obwohl es nach wie vor keine etablierte Therapie gibt, stehen die Chancen gut, dass in Zukunft zumindest einem Teil der RP-Patienten eine Therapie angeboten werden kann.
Supplementary Material for: Long-Term Structural and Functional Assessment of Doyne Honeycomb Retinal Dystrophy Following Nanosecond 2RT Laser Treatment. Case Series.
AbstractIntroduction. Doyne honeycomb retinal dystrophy (DHRD), or autosomal dominant radial drusen, is a genetic disease caused by pathogenic variants of the epidermal growth factor-(EGF)-containing fibulin-like extracellular matrix protein 1 EFEMP1 gene and is characterized by the formation of subretinal drusenoid deposits. In a previous study, we reported the short-term beneficial effects of nanosecond laser treatment (2RT) on retinal function in DHRD. The aim of the present report is to describe the findings of a long-term follow-up of retinal structure/function in a small case series of patients with DHRD who underwent 2RT treatment. Case presentation. Three DHRD patients (case 1, male, and cases 2 and 3, two sister females, age range 41-46) with EFEMP1 pathogenic variant (c.1033C>T; p.R345W) and drusenoid deposits at the posterior pole were examined at baseline and after 2RT treatment, at regular intervals (every 2-4 months) up to 30 months. All three patients underwent one or two treatment sessions in one or both eyes during the follow-up period. Case 3 was treated with only the left eye (LE). Each patient underwent a full ophthalmologic examination, spectral domain optical coherence tomography (OCT), central perimetry with frequency doubling technology (FDT), and mesopic and photopic Ganzfeld electroretinograms. Compared to baseline findings, during follow-up, visual acuity improved in both eyes in case 1 and LE in case 2, while it decreased in the right eye (RE) in case 2 and LE in case 3; perimetric sensitivity was stable in case 1 and improved in both eyes in cases 2 and 3; and electroretinogram amplitude improved in cases 1 and 2, and was stable in case 3 (both eyes). OCT central macular thickness and retinal structure were stable in all cases. None of the patients had treatment-related side effects. Conclusion. This is the first report showing that in a long-term follow-up, 2RT treatment in DHRD may improve or stabilize some retinal function parameters without significant structural changes.
Supplementary Material for: Long-Term Structural and Functional Assessment of Doyne Honeycomb Retinal Dystrophy Following Nanosecond 2RT Laser Treatment. Case Series.
AbstractIntroduction. Doyne honeycomb retinal dystrophy (DHRD), or autosomal dominant radial drusen, is a genetic disease caused by pathogenic variants of the epidermal growth factor-(EGF)-containing fibulin-like extracellular matrix protein 1 EFEMP1 gene and is characterized by the formation of subretinal drusenoid deposits. In a previous study, we reported the short-term beneficial effects of nanosecond laser treatment (2RT) on retinal function in DHRD. The aim of the present report is to describe the findings of a long-term follow-up of retinal structure/function in a small case series of patients with DHRD who underwent 2RT treatment. Case presentation. Three DHRD patients (case 1, male, and cases 2 and 3, two sister females, age range 41-46) with EFEMP1 pathogenic variant (c.1033C>T; p.R345W) and drusenoid deposits at the posterior pole were examined at baseline and after 2RT treatment, at regular intervals (every 2-4 months) up to 30 months. All three patients underwent one or two treatment sessions in one or both eyes during the follow-up period. Case 3 was treated with only the left eye (LE). Each patient underwent a full ophthalmologic examination, spectral domain optical coherence tomography (OCT), central perimetry with frequency doubling technology (FDT), and mesopic and photopic Ganzfeld electroretinograms. Compared to baseline findings, during follow-up, visual acuity improved in both eyes in case 1 and LE in case 2, while it decreased in the right eye (RE) in case 2 and LE in case 3; perimetric sensitivity was stable in case 1 and improved in both eyes in cases 2 and 3; and electroretinogram amplitude improved in cases 1 and 2, and was stable in case 3 (both eyes). OCT central macular thickness and retinal structure were stable in all cases. None of the patients had treatment-related side effects. Conclusion. This is the first report showing that in a long-term follow-up, 2RT treatment in DHRD may improve or stabilize some retinal function parameters without significant structural changes.
Indian Journal of Ophthalmology - Case Reports · 2024 · 0 citations · open access
A rare case report of Doyne’s honeycomb retinal dystrophy
AbstractDoyne’s honeycomb dystrophy is a rare hereditary retinal dystrophy where drusens form in the macula and around the optic nerve head, resulting in choroidal neovascularization later. We report the case of a 63-year-old male with metamorphopsia in the right eye (RE) since 6 months. On examination, his visual acuity was 6/6 in both eyes. The anterior segment was normal. Fundus examination showed multiple drusen deposits in the macula and optic nerve head and hyperpigmentation in the macula. OCT showed hyperreflective bumpy retinal pigment epithelial in Bruch’s membrane. Fundus autofluorescence of both showed hyperfluorescence in areas of drusens. Fundus fluorescein angiography of the RE showed hyperfluorescence with central hypofluorescence. The left eye showed areas of blocked hypofluorescence within areas of hyperfluorescence.
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.
