DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cutis laxa — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCutis laxa maps to a 14-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 cutis laxa 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
ATP binding cassette subfamily C member 6 (ABCC6) — ABCC6 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6BZR · 2.79999446301 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Fibulin 5 missense mutations cause autosomal-recessive cutis laxa. Biophysical studies of two cutis laxa mutants found both increased dimerization of the protein, and all tested mutants remained folded, though perturbations to secondary structure were detected. One AMD-associated variant, G412E, showed the largest hydrodynamic radius for the monomer form and the highest levels of aggregation, suggesting it may also be pathogenic. The other AMD-associated mutants showed no gross structural differences, but the authors note they cannot be excluded as pathogenic by disruptions outside the scope of that study, such as disruption of heterointeractions.
Two case reports of acquired cutis laxa describe patients with no systemic involvement and no history of drug intake. One patient had localised disease with preceding cutaneous inflammation and was treated satisfactorily by reconstructive surgery. The other had generalised lesions with no preceding illness, and no satisfactory treatment could be offered. A separate case report of congenital cutis laxa describes a patient who received systematic and sequential treatment based on plastic surgery; the patient was content with the effect, and there were no signs of recurrence after five months. That report recommends a multi-step, systematic, and sequential treatment for congenital cutis laxa, but notes that previous literature on surgical treatment complained of recurrence.
No drug treatment is tested or recommended in any of these abstracts. The pathogenesis of cutis laxa is described as largely unknown. What is still missing is any controlled trial of a pharmacological intervention, any molecular target for drug repurposing, and any patient stratification beyond the distinction between localised and generalised forms. The evidence base remains limited to case reports and basic protein-structure studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Structural Effects of Fibulin 5 Missense Mutations Associated with Age-Related Macular Degeneration and Cutis Laxa
AbstractPURPOSE: AMD has a complex etiology with environmental and genetic risk factors. Ten fibulin 5 sequence variants have been associated with AMD and two other fibulin 5 mutations cause autosomal-recessive cutis laxa. Fibulin 5 is a 52-kDa calcium-binding epidermal growth factor (cbEGF)-rich extracellular matrix protein that is essential for the formation of elastic tissues. Biophysical techniques were used to detect structural changes in the fibulin 5 mutants and to determine whether changes are predictive of pathogenicity. METHODS: Native PAGE, nonreduced SDS-PAGE, size-exclusion column multiangle laser light scattering, sedimentation velocity, and circular dichroism (CD) were used to investigate the mobility, hydrodynamic radii, folding, and oligomeric states of the fibulin 5 mutants in the absence and presence of Ca(2+). RESULTS: CD showed that all mutants are folded, although perturbations to secondary structure contents were detected. Both cutis laxa mutants increased dimerization. Most other mutants slightly increased self-association in the absence of Ca(2+) but this was also demonstrated by G202R, a polymorphism detected in a control individual. The AMD-associated mutant G412E showed lower-than-expected mobility during native-PAGE, the largest hydrodynamic radius for the monomer form and the highest levels of aggregation in both the absence and presence of Ca(2+). CONCLUSIONS: The results identified structural differences for the disease-causing cutis laxa mutants and for one AMD variant (G412E), suggesting that this may also be pathogenic. Although the other AMD-associated mutants showed no gross structural differences, they cannot be excluded as pathogenic by differences outside the scope of this study-for example, disruption of heterointeractions.
Indian Journal of Dermatology · 2013 · 11 citations · open access
Cutis laxa: A report of two interesting cases
AbstractCutis laxa is a rare disease that may be either inherited or acquired. The acquired form is rarer than the inherited form. Pathogenesis of this disease is largely unknown. Two cases of acquired cutis laxa are reported here and neither of them had any systemic involvement or any history of drug intake. One of them had localized disease with history of preceding cutaneous inflammation. The other patient with generalized lesion lacked any history of preceding illness. The patient with localized lesion was treated satisfactorily by reconstructive surgery. The other patient had generalized involvement, for which no satisfactory treatment could be offered.
INDIGO (University of Illinois at Chicago) · 2022 · 0 citations · open access
Data_Sheet_1_Congenital Cutis Laxa: A Case Report and Literature Review.docx
Abstract<p>Cutis Laxa is a rare connective tissue disease featuring inelastic and saggy skin. It is thought that plastic surgery might be the most effective treatment, while the previous pieces of literature on the surgical treatment for Cutis Laxa complained of the recurrence. We report a patient of Congenital Cutis Laxa who has received systematic and sequential treatment based on plastic surgery. The patient is content with the effect of treatment, and there are no signs of recurrence after 5 months. By referring to relevant pieces of literature, we evaluate the clinical manifestations and diagnosis of the disease. A multi-step, systematic, and sequential treatment is recommended for the treatment of Congenital Cutis Laxa.</p>
AbstractABSTRACTCutis laxa is an uncommon disorder characterized clinically laxitiy of the skin, which hangs in loose folds, by the loss of dermal elastic tissue. We report a case only neck localized of cutis laxa that no systemic involvement was diagnosed. The skin laxity was preceded by episodes of itching and swelling on her neck. When the patient applied to our clinic, she was considered as a case of localized cutis laxa, and the patient was recovered by neck lift operation. Histopathology showed that the elastic fibers were lost in the skin areas of cutis laxa and decreased in adjacent skin. The pathogenetic relationship with any other disorder or intake of related drug could not found. J. Exp. Clin. Med., 2011; 28:31-32
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.
