DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal dominant Alport syndrome — 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 moduleAutosomal dominant Alport syndrome 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 autosomal dominant alport syndrome 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
coat protein complex I subunit alpha (COPA) — COPA 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 +drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6PBG · 1.72 Å · ligand L(+)-TARTARIC ACID (TLA). Experimental structure, not a prediction.
What the evidence adds up to
In a retrospective Japanese study of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (72 patients total from 16 families), the median renal survival time was 70 years and the median age at first detection of proteinuria was 17 years. Among 16 patients who underwent kidney biopsy, three showed FSGS and seven showed thinning without lamellation of the glomerular basement membrane. Only one patient had hearing loss and one had an ocular lesion. The study concluded that the renal phenotype was much milder than that of autosomal recessive or X-linked Alport syndrome, and that no modifier genes were identified among the known podocyte-related genes.
A separate 2025 case report describes a 78-year-old man diagnosed with autosomal dominant Alport syndrome during evaluation in a nephrology clinic, noting that the diagnosis is often missed in patients with chronic kidney disease of unknown origin unless specific genetic testing is performed. The 2020 abstract states that the autosomal dominant form represents 10–15% of Alport syndrome cases, while the 2016 study found it accounts for less than 5% of patients. The 2016 study also found that five of 13 detected mutations had previously been reported as causative for autosomal recessive Alport syndrome, and two families possessed double mutations in both COL4A3 and COL4A4.
The clinical presentation is variable but generally milder than the X-linked or autosomal recessive forms, making accurate diagnosis difficult on the basis of clinical or pathologic findings alone. No trial has tested any drug specifically for autosomal dominant Alport syndrome. What is missing is a prospective trial designed for this population, which would require patient stratification by genotype and baseline proteinuria, and funding for long-term follow-up given the slow progression to end-stage renal disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Journal of the American Society of Nephrology · 2016 · 135 citations
Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome
AbstractBACKGROUND AND OBJECTIVES: Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport-related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. RESULTS: The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte-related genes. CONCLUSIONS: The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X-linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte-related genes.
Kidney International Reports · 2020 · 0 citations · open access
SUN-452 X-LINKED ALPORT SYNDROME: FIRST CASE DESCRIBED IN CHAD IN A 19-YEAR-OLD PATIENT
AbstractAlport's syndrome is a rare inherited disorder, characterized by a combination of hematuric glomerular nephropathy that progresses to end-stage renal failure, perceptual deafness, and ocular involvement. It is a collagen IV disease, the main constituent of basement membranes, linked to mutations in the genes encoding one of the three chains, α3, α4 or α5 (IV), expressed in the glomerular basement membrane. The autosomal dominant form represents 10-15%, whereas the autosomal recessive form is rare.
Autosomal Dominant Alport Syndrome Diagnosed in an Elderly Man
AbstractAutosomal dominant Alport syndrome (ADAS) is an uncommon diagnosis and is often missed in patients with chronic kidney disease of unknown origin unless specific genetic testing is performed. It results from heterozygous mutations in the COL4A3 and COL4A4 genes. The clinical presentation is variable but generally milder than that of X-linked or autosomal recessive Alport syndrome. In this article, we present the case of a 78-year-old man who was diagnosed with ADAS during evaluation in a nephrology clinic. We also discuss the condition and the challenges related to the terminology surrounding Alport syndrome.
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.
