DeCure for Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleContractures, pterygia, and spondylocarpotarsal fusion syndrome 1A maps to a 1-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 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 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.
What the evidence adds up to
A single case report describes an 18-month-old boy with congenital spondyloptosis of L5-S1 who underwent a staged surgical procedure: L5 laminectomy with bilateral L5 nerve root decompression, anterior subtotal resection of L5 with interbody bone graft from L5 to S1, reduction of the spondyloptosis, and posterior instrumentation from L2 to S1 using a sacral Cotrel-agraffe device. The procedure achieved almost complete reduction of the spondyloptosis with near-normal restoration of lumbar lordosis. No neurologic complications occurred, and at follow-up there was no suggestion of back pain or gait disturbance and no progression of deformity. This is a single patient with no control group, and the surgery is specific to spinal deformity, not a drug treatment for the underlying syndrome.
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A (CPSFS) is caused by variants in MYH3. A 2024 report describes two affected siblings with distal arthrogryposis born to unaffected, distantly related parents. Both siblings were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic MYH3 variants causing a distal arthrogryposis phenotype without the additional bony features of CPSFS. No treatment or intervention was tested in this genetic study.
A 2013 case report describes a 7-year-old boy with spondylocarpotarsal synostosis syndrome who also had urolithiasis. The authors state this association had not been reported before. No treatment for the syndrome itself is discussed.
A 1984 case report describes a girl in Japan with multiple pterygium syndrome, including pterygia of neck, antecubital, digital, popliteal, and intercrural areas, growth retardation, peculiar facies, foot deformities, multiple joint contractures, and vertebral anomalies. The case was sporadic with mild symptoms and no family history. No treatment is described.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Spine · 2001 · 20 citations
Treatment of Congenital Spondyloptosis in an 18-Month-Old Patient With a 10-Year Follow-Up
AbstractSTUDY DESIGN: Case report. OBJECTIVES: To present the case of a patient with congenital spondyloptosis treated and followed over 10 years. SUMMARY OF BACKGROUND DATA: The surgical management of spondyloptosis in children is variably reported in the literature. Some authors propose that posterior fusion in situ is a safe and reliable procedure, whereas others suggest that reduction of the slipped vertebra may prevent some of the adverse sequelae of in situ fusion, which include nonunion, bending of the fusion mass, and persistent lumbosacral deformity. Many investigators advocate a combined anterior and posterior fusion using instrumentation. METHODS: At the time of the first symptoms an 18-month-old boy with congenital spondyloptosis of L5-S1 was referred to the authors' institution. Because of the progression of pain, neurologic disturbance, mild foot deformity, muscle contractures, and lumbosacral kyphosis, surgical intervention was undertaken. Operative intervention began with a resection of the L5 lamina and wide bilateral L5 nerve root decompression. This was followed by anterior subtotal resection of L5 and interbody bone graft of the morcelized vertebral body for fusion from L5 to S1. The next step was reduction of the spondyloptosis and stabilization by posterior instrumentation L2-S1 with a sacral Cotrel-agraffe device. RESULTS: The procedure achieved almost complete reduction of the spondyloptosis with near-normal restoration of lumbar lordosis allowing more physiologic lumbar spinal biomechanics. There were no neurologic complications. After surgery there was no suggestion of back pain or gait disturbance and no progression of any deformity. CONCLUSION: In the treatment of severe congenital spondylolisthesis a staged procedure of decompression, reduction, and instrumented fusion is recommended for those cases in which intervention is indicated.
Clinical Genetics · 2024 · 3 citations · open access
Bi‐allelic variants in <scp>MYH3</scp> cause recessively‐inherited arthrogryposis
AbstractArthrogryposis is a clinical feature defined by congenital joint contractures in two or more different body areas which occurs in between 1/3000 and 1/5000 live births. Variants in multiple genes have been associated with distal arthrogryposis syndromes. Heterozygous variants in MYH3 have been identified to cause the dominantly-inherited distal arthrogryposis conditions, Freeman-Sheldon syndrome, Sheldon-Hall syndrome, and multiple pterygium syndrome. In contrast, MYH3 variants underlie both dominantly and recessively inherited Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterized by extensive bony abnormalities in addition to congenital contractures. Here we report two affected sibs with distal arthrogryposis born to unaffected, distantly related parents. Sequencing revealed that both sibs were homozygous for two ultra-rare MYH3 variants, c.3445G>A (p.Glu1149Lys) and c.4760T>C (p.Leu1587Pro). Sequencing and deletion/duplication analysis of 169 other arthrogryposis genes yielded no other compelling candidate variants. This is the first report of biallelic variants in MYH3 being implicated in a distal arthrogryposis phenotype without the additional features of CPSFS. Thus, akin to CPSFS, both dominant and recessively inherited distal arthrogryposis can be caused by variants in MYH3.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · 2013 · 3 citations · open access
Urolithiasis in a child with Spondylocarpotarsal Synostosis Syndrome: A Co-Incidence
AbstractSpondylocarpotarsal synostosis syndrome (SSS) is an autosomal recessive condition which is characterized by short stature, a carpotarsal coalition and a vertebral fusion, but without any rib anomaly. We are presenting a 7- year- old boy, who had uroliathiasis with the spondylocarpotarsal synostosis syndrome. This association, to the best of our knowledge, has not been reported so far.
AbstractThe multiple pterygium syndrome is a rare condition which consists of pterygia of neck, antecubital, digital, popliteal, and intercrural areas, growth reteardation, peculiar facies, foot deformities, multiple joint contractures, vertebral anomalies. Here we report a girl with multiple pterygium syndrome. This case is a sporadic type because of mild symptom and no evidence in her family history. We believe this is the first reported case of the multiple pterygium syndrome in Japan.
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.
