DeCure for Degeneration of macula and posterior pole
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for degeneration of macula and posterior pole — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDegeneration of macula and posterior pole maps to a 35-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
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside degeneration of macula and posterior pole in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
TetR(D) — Minocycline has a real, experimentally solved structure in complex with this target (PDB 2XPV, 1.49 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet miydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2XPV · 1.49 Å · ligand Minocycline (MIY). Experimental structure, not a prediction.
What the evidence adds up to
A spontaneous nonhuman primate model of inherited macular dystrophy has been reported, carrying a heterozygous BEST1 p.Q327E variant that disrupts the ion channel. Longitudinal imaging over two years showed progressive macular changes including subfoveal cleft enlargement, lipid-rich deposit accumulation, retinal pigment epithelium disruption, and central-to-peripheral photoreceptor degeneration, recapitulating early human Best vitelliform macular dystrophy pathology. Histopathology revealed diminished BEST1 expression, attenuation of the RPE-photoreceptor interface, and two distinct types of lipid deposits, including cone mitochondrial-enriched lesions. This is the first nonhuman primate model of inherited macular dystrophy, linking BEST1 mutations, mitochondrial dysfunction, and progressive macular degeneration.
Age-related macular degeneration is the leading cause of visual impairment in developed countries. Dry AMD accounts for 85-90% of cases and involves apoptosis of RPE cells and subsequent photoreceptor death in the macula. Wet AMD contributes to 90% of severe vision loss and is driven by choroidal neovascularisation. Anti-VEGF agents have become the main medical treatment for wet AMD. Surgical treatments such as macula translocation, submacular surgery, and RPE transplantation exist but are limited to selected cases due to high complication rates and difficult techniques.
Fundus photographs from patients with inherited retinal degenerations show progressive macular changes across different genotypes. In AIPL1 mutation carriers, yellow patches and black pigments appeared in the macula. RPE65 mutation carriers showed macular scars and peripheral RPE mottling. CRB1 mutation carriers displayed coin-shaped pigment clumps and greyish atrophic changes in the macula, with progressive worsening across three affected siblings. MERTK mutation carriers showed mild to marked features of retinitis pigmentosa with progressive macular changes by age.
What is still missing are treatments that address the underlying mechanisms of both inherited and age-related macular degeneration, particularly for the dry form which lacks any approved therapy. The primate model may enable testing of gene therapies and other interventions, but no therapeutic results from that model are yet reported. Clinical trials for dry AMD remain scarce, and no drug has shown ability to halt or reverse geographic atrophy in a large randomised study. Patient stratification by genetic subtype and disease stage is not yet standard, and funding for long-term studies of slow-progressing macular diseases is limited.
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 Ophthalmology · 2009 · 40 citations
Minocycline Inhibition of Photoreceptor Degeneration
AbstractOBJECTIVE: To determine whether systemic minocycline can protect photoreceptors in experimental retinal detachment (RD). METHODS: Retinal detachment was induced in mice by subretinal injection of sodium hyaluronate, 1.4%. In 1 experiment, mice received daily injections of minocycline (group 1) or saline (group 2). In a second experiment, mice were treated with minocycline or saline beginning 24 hours prior, immediately after, or 24 hours after experimental RD. In both experiments, photoreceptor cell survival and apoptosis were assessed by immunohistochemistry with primary antibodies against photoreceptor cell markers, rod rhodopsin, and cone opsin, and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling. RESULTS: Photoreceptor cell apoptosis was detected at day 1 after experimental RD, with apoptotic cells peaking in number at day 3 and dropping by day 7. Treatment with minocycline significantly reduced the number of apoptotic photoreceptor cells associated with RD when given 24 hours before or even 24 hours after RD. CONCLUSIONS: Our data suggest that minocycline may be useful in the treatment of photoreceptor degeneration associated with RD, even when given up to 24 hours after RD. CLINICAL RELEVANCE: Use of minocycline in patients with macula-off RD may prevent photoreceptor apoptosis and glial cell proliferation, improving final visual outcomes.
A spontaneous nonhuman primate model of inherited retinal degeneration
AbstractInherited retinal degenerations (IRDs) are important causes of progressive, irreversible blindness. Hereditary macular diseases, in particular, are significant in their effect on the specialized, central cone photoreceptor-rich macula responsible for high resolution vision. Autosomal dominant Best vitelliform macular dystrophy (BVMD), caused by variants in the BEST1 gene, is one of the most common inherited macular dystrophies. Gene therapies have emerged as promising treatments for IRDs, but a lack of suitable animal models has hindered progress both in treatments and in understanding the mechanisms underlying macular diseases. Here, we report a Macaca fascicularis carrying a heterozygous potential pathogenic BEST1p.Q327E variant that disrupts the BEST1 ion channel by destabilizing the A195 helix, mirroring the structural perturbations seen in certain human pathological mutants. Longitudinal imaging over 2 years revealed progressive macular changes, including subfoveal cleft enlargement, lipid-rich deposit accumulation, retinal pigment epithelium (RPE) disruption, and central-to-peripheral photoreceptor degeneration, recapitulating early human BVMD pathology. Histopathology demonstrated diminished BEST1 expression, attenuation of the RPE-photoreceptor interface, and 2 distinct types of lipid deposits, including heretofore unappreciated cone mitochondrial-enriched lesions, highlighting selective cone mitochondria vulnerability. This is, to our knowledge, the first nonhuman primate model of inherited macular dystrophy, and it links BEST1 mutations, mitochondrial dysfunction, and progressive macular degeneration, offering new insights into BVMD pathophysiology and highlighting its utility for studying disease progression and potential therapeutic interventions.
Inflammation in Age-Related Macular Degeneration – Implications for Therapy
AbstractThe macula or macula lutea (originally from Latin macula, “spot” and lutea, “yellow”) is an oval-shaped spot, five mm in diameter, located temporal to the optical nerve and near the centre of the human retina. Although it comprises only a small part of the retina, it is responsible for the sharp central vision and colour vision. Age-related macular degeneration (AMD) is a disease in which the neuroretina and retinal pigment epithelia (RPE) of the macula degenerate with age resulting in profound loss of visual function. At the early stages, so called age-related maculopathy, patients present with “drusen”, the “biological waste materials” deposition, between RPE cells and the choroid especially in the macular region (Coleman et al. 2008, Jager et al. 2008). Visual acuity is normally not affected at this stage. As disease progresses to the advanced stages, patients may lose their central vision. There are two forms of advanced AMD: dry and wet. Dry-AMD also called central geographic atrophy. Apoptosis of RPE cells and subsequent death of photoreceptors in the macula underlie the pathology of dry-AMD (Coleman et al. 2008). “Wet” AMD refers to the neovascular or exudative form of the disease and is associated with rapid vision loss caused by the infiltration of abnormal blood vessels from the choroid into the subretinal space leading to haemorrhage, leakage of fluid and eventual scar tissue formation (Chopdar et al. 2003, Coleman et al. 2008). Dry-AMD is more common than wet-AMD accounting for nearly 85~90% of AMD cases; however, wet-AMD contributes to 90% of severe vision loss resulting from AMD (Chopdar et al. 2003). In addition, AMD is generally thought to progress along a continuum from atrophic or dry-AMD to neovascular (wet) AMD with approximately 1015% of all AMD patients eventually developing the wet form (Sunness et al. 1999). Occasionally, patients can also present with exudative (wet) AMD as the first manifestation of the condition without prior signs of dry-AMD.
Güncel Retina Dergisi (Current Retina Journal) · 2017 · 0 citations · open access
Surgical Treatment in Wet-Form (Neovascular) Age-Related Macular Degeneration
AbstractAge-related macular degeneration (AMD) is the leading cause of visual impairment in developed countries. Studies have been going on for the treatment of an exudative form of the disease for years. In recent years after the investigation of anti-VEGF agents, medical treatments have become the main treatment option for this disease. Surgical treatment modalities are macula translocation, submacular surgery, and retina pigment epithelium (RPE) transplantation. Nowadays because of high complication rates and difficult surgical techniques surgical treatment use only chose cases with limited indications.
Abstract<p>Fig 3a A 10yrs old female with c.824G>A p.(Trp278*) mutation in <i>AIPL1</i> (LCA-5 family) showed normal disc, attenuated vessels, (arrow mark indicates) yellow patches in macula. Fig 3b A 14yrs old male with c.824G>A p.(Trp278*) mutation in <i>AIPL1</i> (LCA-5 family, elder sibling) showed normal disc, attenuated vessels, (arrow mark indicates) black pigments in macula. Fig 3c A 18 yrs old female with c.850+1G>T (r.spl?) mutation in <i>RPE65</i> (LCA-1 family) showed pallor disc, attenuated vessels with scar in the macula, peripheral RPE mottling (marked with arrow) Fig 3d A 28yrs old male with c.1409C>T p.(Pro470Leu) mutation in <i>RPE65</i> (LCA-9 family) showed pallor disc, attenuated vessels, normal macula, with salt and pepper fundus. Arrow mark shows distinct pin head size yellow white dot like spots at the posterior pole. Fig 3e A 14 yrs old female with c.2971G>A p.(Gly991Arg) mutation in <i>CRB1</i> (LCA-2 family) showed coin shaped pigment clumps and greyish atrophic changes seen in the macula, (arrow mark indicates the macula) Fig 3f A 18 yrs old female with c.2971G>A p.(Gly991Arg) mutation in <i>CRB1</i> (LCA-2 family, elder sibling) showed pale disc, attenuated vessels, atrophic macula with nummular pigment clumps and greyish atrophic reflex (arrow mark indicates the macula) Fig 3g A 19yrs old male female with c.2971G>A p.(Gly991Arg) mutation in <i>CRB1</i> (LCA-2 family, eldest sibling) showed coin shaped pigment clumps seen in the background (arrow mark indicates the coin shaped clumps) All the three affected siblings show progressive changes in macula with age for <i>CRB1</i> mutation positive family. Fig 3h, 3i, 3j A 24 yrs old female, a 25 yrs old female and a 32 yrs old female with c.721C>T p.(Gln 241*) mutation in <i>MERTK</i> (arRP1 family) showing mild, milder and marked features of RP, respectively. Progressive changes with age in the macula are observed.</p>
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.
