DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for restrictive dermopathy 1 — 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 moduleRestrictive dermopathy 1 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 restrictive dermopathy 1 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
zinc metallopeptidase STE24 (ZMPSTE24) — ZMPSTE24 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 pc1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AW6 · 3.4 Å · ligand 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (PC1). Experimental structure, not a prediction.
What the evidence adds up to
Restrictive dermopathy is a rare and lethal autosomal recessive genodermatosis. Two siblings with the condition died in the neonatal period, and molecular analysis of one child identified compound heterozygous frameshifting mutations in exon 1 (c.50delA) and exon 5 (c.584_585delAT) of the ZMPSTE24 gene, with autosomal recessive inheritance confirmed by parental testing. A separate report of two further siblings also found a familial c.50delA (p.Lys17Serfs*21) mutation in ZMPSTE24. The disease can also be caused, less frequently, by LMNA autosomal dominant mutations. About 60 cases had been described by 2010.
The clinical features are characteristic: intrauterine growth retardation, thin tightly adherent translucent skin with prominent superficial vessels, typical facial dysmorphism, and generalised joint contractures. Histological findings from two sibs who died in the neonatal period showed abnormal integrin expression in cultured fibroblasts, with increased expression of the alpha-1 and alpha-2 integrin subunits responsible for collagen binding. The increase was not matrix dependent, and the authors proposed that restrictive dermopathy is a disorder of skin differentiation.
One abstract concerns diabetic dermopathy, a completely different condition involving small brown atrophic lesions on the shins of diabetic patients. That abstract is irrelevant to restrictive dermopathy and contains no information about ZMPSTE24, LMNA, or neonatal lethal genodermatosis.
No treatment or intervention for restrictive dermopathy is described in any of these abstracts. The disease remains uniformly lethal in the neonatal period. What is missing is any clinical trial, any attempt at prenatal or postnatal therapy, any animal model of the ZMPSTE24 mutations, and any systematic effort to stratify patients by mutation type or to develop a screening programme for at-risk families.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2010 · 48 citations
Novel frameshifting mutations of the <i>ZMPSTE24</i> gene in two siblings affected with restrictive dermopathy and review of the mutations described in the literature
AbstractRestrictive dermopathy (RD) is a rare, severe, lethal genodermatosis in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence. To date, about 60 cases of RD were described. The signs of the disease are very characteristic and include intrauterine growth retardation, thin, tightly adherent translucent skin, superficial vessels, typical facial dysmorphism as well as generalized joint contractures. The syndrome is caused in most cases by ZMPSTE24 autosomal recessive mutations, or, less frequently, by LMNA autosomal dominant mutations. We report on two brothers affected with RD, who died in the neonatal period. Molecular analyses were performed in the second child, for whom biological material was available, and both parents. Compound heterozygous frameshifting mutations were identified in exon 1 (c.50delA) and exon 5 (c.584_585delAT) of the ZMPSTE24 gene. The autosomal recessive inheritance was confirmed by the parents' genomic analysis. Besides, a review of the mutations causing RD is made.
Frame shift mutations of the ZMPSTE24 gene in two siblings with restrictive dermopathy
AbstractRestrictive dermopathy (RD) is a rare lethal autosomal recessive genodermatosis, characterized by abnormally rigid skin with prominent superficial vasculature, erosions and epidermal hyperkeratosis, dysplastic clavicles, joint contractures, mouth fixed in the 'O' position, small pinched nose, and neonatal death. Mutations of ZMPSTE24 and LMNA genes are reported as the causes of RD, with those of ZMPSTE24 being more prevalent. Here, we report on a familial c.50delA (p.Lys17Serfs*21) mutation of the ZMPSTE24 gene, causing RD in two siblings.
Journal of Evidence Based Medicine and Healthcare · 2015 · 0 citations · open access
CLINICAL ANALYSIS OF DIABETIC DERMOANGIOPATHY IN A TERTIARY CARE CENTER IN CHHATTISGARH
AbstractINTRODUCTION \nDiabetic dermopathy is a term used to describe the small, round, brown atrophic skin lesions that occur on the shins of patients \nwith diabetes. The lesions are asymptomatic and occur in up to 55% of patients with diabetes. One hundred diabetic patients \nand 100 non-diabetic controls were examined for lesions of diabetic dermoangiopathy. Twenty two (22%) diabetic persons \nhave lesions in contrast to only two (2%) people in controls. Diabetic dermopathy was more common in older patients mostly \nin fifth to the seventh decade and those with longstanding diabetes. There was no statistical significant relationship with the \nsex, type, severity of diabetes, diabetic neuropathy and macroangiopathy like CAD, PVD or CVA. Dermopathy was also more \ncommon (31.5%) among the persons whose duration of diabetes was more than 5 years, than if it was less than 5 years \n(16.1%). Seven (38.8%) out of 18 cases of retinopathy also had dermopathy. The underlying mechanism for diabetic \ndermopathy is unknown, although it may be related to local thermal trauma, decreased blood flow causing impaired wound \nhealing or local subcutaneous nerve degeneration. Diabetic dermopathy requires no treatment, but may be a surrogate for \nother complications of diabetes, which require investigation and management. \n
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.
