DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for scleroderma — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleScleroderma maps to a 12-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
approvedMepivacaineApproved drug
Structures already discussed alongside scleroderma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
sodium voltage-gated channel alpha subunit 9 (SCN9A) — SCN9A is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has o-[(r)-{[(2r)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-l-serine bound in it, shown as sticks.
Loading structure…
helix sheet rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7W9K · 2.2 Å · ligand O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine (P5S). Experimental structure, not a prediction.
What the evidence adds up to
Localised scleroderma was observed in 115 patients at the University of Michigan between 1932 and 1955. The authors note that reports of various treatments for localised scleroderma continued to appear, but with limited knowledge of the natural course of the untreated disease and often a lack of control observations, any true evaluation of therapeutic effectiveness or failure could only be presumptive. It was generally assumed the disease was self-limited and without serious complications.
A 1998 review states that although the clinical course of localised scleroderma is often benign, widespread lesions and disabling joint contractures may lead to significant complications. The pathogenesis of the different types remains unknown. Numerous therapeutic agents have been reported effective, but controlled studies are rare.
For systemic sclerosis, a 2010 review of innovative therapies reports that preliminary data from early clinical trials suggest tyrosine kinase molecules may be potential candidates, especially in the fibrotic phase. T-cell-directed therapies including halofuginone, basiliximab, alemtuzumab, abatacept and rapamycin have been proposed to be clinically beneficial. Recent clinical studies with rituximab in diffuse cutaneous systemic sclerosis lend support that B cells may be important. Statins, endothelin receptor antagonists and phosphodiesterase type V inhibitors have been shown useful for vascular manifestations. Haematopoietic stem cell transplantation following immune ablation holds promise, and trial results were awaited. The review concludes there is still no treatment unequivocally effective for scleroderma.
What is still missing are large, multicentre, randomised controlled trials for the candidate therapies identified, and controlled studies for localised scleroderma where the natural history remains poorly documented. Patient stratification and long-term follow-up data are also lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Rheumatology · 2006 · 377 citations
Localized scleroderma
AbstractPURPOSE OF REVIEW: Localized scleroderma, also known as morphoea, has a variety of clinical manifestations that can include systemic involvement. Early recognition, diagnosis and treatment may improve the long-term outcome. RECENT FINDINGS: A large multicentre study coordinated by the Pediatric Rheumatology European Society has yielded important information on the epidemiology and clinical manifestations of juvenile localized scleroderma, especially as it pertains to systemic manifestations. Previous results using methotrexate and corticosteroids have been confirmed. Studies on phototherapy have also demonstrated efficacy. A new immunomodulator, imiquimod, has shown promise in an initial case series. SUMMARY: Studies over the past year highlight the wide range of extracutaneous manifestations and different forms of localized scleroderma and suggest that treatment may be beneficial.
AbstractWhile much interest has been given to the generalized systemic forms of scleroderma, relatively little information has appeared about localized scleroderma. Reports concerning the use of various therapeutic agents in localized scleroderma continue to appear, but with a limited knowledge of the natural course of the untreated disease and often a lack of control observations any true evaluation of therapeutic effectiveness or failure can only be presumptive. Dowling 1 has stated, . . at present, there is not very much that one can usefully say about it. In an effort to obtain some information regarding the prognosis in treated and untreated patients, we have summarized the records of 115 patients who had localized scleroderma and who were observed at the University Hospital (Michigan) between 1932 and 1955. It is generally assumed that the disease is self-limited and without serious complications. Much of the evidence for the benign character
Seminars in Cutaneous Medicine and Surgery · 1998 · 58 citations
Management of localized scleroderma
AbstractLocalized scleroderma denotes a spectrum of conditions characterized by circumscribed fibrotic areas involving different levels of the dermis, subcutis, and sometimes underlying soft tissue and bone. Although the clinical course of the disease is often benign, widespread lesions and disabling joint contractures may lead to significant complications. The pathogenesis of the different types of localized scleroderma is still unknown. Numerous therapeutic agents have been reported to be effective in this disease spectrum, but controlled studies are rare. The purpose of this review is to summarize previous experience and to discuss recent advances in the management of localized scleroderma.
Current Opinion in Rheumatology · 2010 · 41 citations
Innovative therapies for systemic sclerosis
AbstractPURPOSE OF REVIEW: The purpose of this study is to review the evidence and recent developments leading to novel therapeutics in scleroderma. RECENT FINDINGS: Recent advances have been made in understanding the key pathogenetic aspects of scleroderma, and these have led to potential targeted therapeutic agents for the management of these patients. Preliminary data from early clinical trials suggest that tyrosine kinase molecules may be potential candidates for therapy, especially in the fibrotic phase of the disease. On the basis of the new insights into the key role of effector T cells, in particular Th-17 and T regulatory subsets, T-cell-directed therapies including halofuginone, basiliximab, alemtuzumab, abatacept and rapamycin have been proposed to be clinically beneficial. By analogy, recent clinical studies with rituximab in diffuse cutaneous systemic sclerosis lend support that B cells may be important in the pathogenesis of the disease. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, endothelin receptor antagonists and phosphodiesterase type V inhibitor have been shown to be useful to treat the vascular manifestations associated with systemic sclerosis. Haematopoietic stem cell transplantation following immune ablation holds considerable promise in resetting of the immune system, and trial results are awaited. SUMMARY: Although there is still no treatment that is unequivocally effective for scleroderma, there have been some promising developments over the past number of years with identification of novel candidate targets and innovative strategies, including targeted immunomodulatory therapies, tyrosine kinase inhibitors and agents that may promote vascular repair. These recent findings will need to be confirmed by larger, multicentre, randomized controlled trials, but they provide hope that these novel therapeutic agents may broaden the currently restricted therapeutic armamentarium of the disease.
Orphanet Journal of Rare Diseases · 2011 · 15 citations · open access
Lidocaine for systemic sclerosis: a double-blind randomized clinical trial
AbstractBACKGROUND: Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. The aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma. METHODS: A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. OUTCOMES: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ). RESULTS: There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them. CONCLUSIONS: Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means.
Linear scleroderma after contusion and injection of mepivacaine hydrochloride
AbstractA 36-year-old woman initially was treated for a contusion by local injection of mepivacaine hydrochloride into the left dorsum of the foot. Approximately 3 months after the injury and injection, linear sclerotic plaques originating from the site of contusion and injection were recognized. These progressed in extent and severity over a period of 3 years, when she presented to our clinic. By biopsy, swelling of collagen fibers in the lower dermis was revealed and the condition was diagnosed as linear scleroderma. Our present case had multiple linear sclerotic plaques of the left lower extremity, the distribution of which was consistent with Blaschko lines. It was also revealed that the initial sclerotic plaque was at the site of the contusion and local mepivacaine hydrochloride injection. Our present case is interesting in that the findings suggest a correlation between linear scleroderma plaque occurrence and the contusion or injection of mepivacaine.
International Journal of Surgery Case Reports · 2017 · 10 citations · open access
Systemic sclerosis
AbstractINTRODUCTION: Systemic sclerosis is a rare and progressive multisystem autoimmune disorder that is characterized pathologically by vascular abnormalities, connective tissue sclerosis and atrophy of skin and various internal organs (e.g., alimentary tract, lungs, heart, kidney, CNS), and autoantibodies. With an unknown etiology, Scleroderma is a complex polygenetic disease. A recent Genome Wide Association Study (GWAS) confirmed a strong association with the Major Histocompatibility Complex (MHC) and autoimmunity. We provide a case scenario along with a review of the systems involved and challenges physicians can face in dealing with this rare disease. CASE PRESENTATION: Our patient, a known case of systemic sclerosis, was admitted with a history of right femur fracture following a fall. We highlight the medical, anesthetic and surgical challenges faced by our team in the management of this patient. We will explain the stages patient faced in treatment process till her death. We combined the case report with detailed literature review of this rare disease. DISCUSSION: Systemic sclerosis is a complex disease process with many different levels of system involvement. Patient needs to be reviewed thoroughly in preoperative period by multidisciplinary team and counseled in detail about the difficulties in procedure, risks and complications. CONCLUSION: Patient with scleroderma presents a challenge to the surgical team and anesthetist and a multidisciplinary approach should be followed with all of these patients to avoid catastrophic results.
The International Journal of Prosthodontics · 2014 · 8 citations
A Simple and Effective Method for Prosthetic Rehabilitation in Scleroderma Patients: A Clinical Report
AbstractTreatment of patients with microstomia due to scleroderma is complicated. Limited mouth opening and altered finger shape present difficulties at every step of the prosthetic rehabilitation. This article describes the prosthetic management of an edentulous patient with severe microstomia induced by scleroderma. From among the existing treatment options and according to the patient's ability and financial considerations, the authors provided a simple prosthetic design that effectively facilitated the patient's rehabilitation. To plan treatment for a patient with scleroderma, it is important to have knowledge about existing complications, alternative methods, and the patient's ability and comfort.
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.
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