DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lethal congenital contracture syndrome — 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 moduleLethal congenital contracture syndrome 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 lethal congenital contracture 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
adhesion G protein-coupled receptor G6 (ADGRG6) — ADGRG6 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 6ardrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 21DU · 2.9 Å · ligand (6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-10,11-diol (OR9). Experimental structure, not a prediction.
What the evidence adds up to
Lethal congenital contracture syndrome (LCCS) is a specific, prenatally lethal form of arthrogryposis. In a Finnish epidemiological study covering 1987–2002, 39 cases of LCCS were identified among 141 lethal arthrogryposis cases drawn from 214 total cases of multiple contractures. LCCS was characterised by total fetal immobility on all ultrasound examinations from 12 weeks onward, multiple joint contractures in all four limbs, hydrops, and fetal death before the 32nd week of pregnancy. The prevalence of LCCS in Finland was 1 in 25,250 births (0.40 per 10,000 births), making it a major cause of lethal arthrogryposis in that population. Among all 214 cases of multiple contractures, 92 resulted in intrauterine death (68 terminations and 24 stillbirths) and 58 died in infancy.
The broader category of arthrogryposis multiplex congenita occurs in approximately 1 in 3,000 births and can appear in isolation or with other abnormalities. Over 150 conditions are known in which multiple congenital contractures are a predominant sign. The aetiological and genetic basis is very heterogeneous, and a specific diagnosis is required to understand natural history and recurrence risk. In the Finnish study, 59 of the 141 lethal arthrogryposis cases showed spinal cord pathology at autopsy, indicating a neurogenic origin.
No treatment for LCCS itself is described in these abstracts. One abstract reports a single case of a late preterm infant with congenital chylothorax who responded positively to oral sildenafil, but this condition is distinct from LCCS. The chylothorax case is presented as an alternative when somatostatin analogues are unavailable, and the authors note a need for randomised studies to achieve standardised treatment algorithms.
What remains missing for LCCS is any clinical trial data, any drug tested in affected fetuses or neonates, and any understanding of whether the condition could be modified after diagnosis. No patient stratification beyond the neurogenic versus non-neurogenic autopsy finding has been attempted, and no funding for a treatment study has been reported.
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 Orthopaedics and Related Research · 1985 · 143 citations
Genetic Aspects of Arthrogryposis
AbstractMultiple congenital contractures or arthrogryposis is a birth defect that occurs in approximately one in 3000 births. It can be seen in isolation or in association with other abnormalities. The etiologic and genetic basis of multiple congenital contractures is very heterogeneous. In order to understand the genetic basis and natural history of a specific case, a specific diagnosis must be made. Over 150 conditions are known in which multiple congenital contractures are a predominant sign. In this chapter, the emphasis is on a systematic differential diagnosis and consideration of empiric recurrent risk figures if a specific diagnosis cannot be reached.
American Journal of Medical Genetics Part A · 2006 · 74 citations
Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland—An epidemiological study
AbstractArthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.
Journal of Pediatric Orthopaedics · 1985 · 31 citations
GENETIC ASPECTS OF ARTHROGRYPOSIS
AbstractMultiple congenital contractures or arthrogryposis is a birth defect that occurs in approximately one in 3000 births. It can be seen in isolation or in association with other abnormalities. The etiologic and genetic basis of multiple congenital contractures is very heterogeneous. In order to understand the genetic basis and natural history of a specific case, a specific diagnosis must be made. Over 150 conditions are known in which multiple congenital contractures are a predominant sign. In this chapter, the emphasis is on a systematic differential diagnosis and consideration of empiric recurrent risk figures if a specific diagnosis cannot be reached.
BMJ Case Reports · 2011 · 12 citations · open access
Volkmann ischemic contracture in a newborn
AbstractCongenital Volkmann ischemic contracture is a very rare condition in which a neonate presents skin, muscular and nerve lesions due to increased intracompartment pressure and subsequent ischemia, probably due to extrinsic intrauterine compression. In this age group, there are only about 50 reported cases and a specific cause is unknown. The authors describe the case of a newborn who presented with bullous and ulcerated skin lesions and nerve palsy of his forearm at birth, evolving to subcutaneous and muscular necrosis and contracture. Two surgeries were performed and the baby began a daily physiotherapy program that resulted in aesthetical improvement and recovery of his hand and forearm mobility. Early recognition of this rare entity and subsequent emergency fasciotomy are the best ways to improve prognosis.
The Newborn Reviews & Research · 2024 · 0 citations · open access
Oral sildenafil, an alternative treatment for congenital chylothorax - Case presentation and review of the literature
AbstractBackground. Congenital chylothorax is a rare but potentially lethal condition characterized by the accumulation of chyle in the pleural cavity during fetal life. The etiology is vast, and treatment is challenging. Thus, different approaches are followed, but no standardized guidelines are available. The general strategy is to initiate supportive, conservative therapy, and as needed, more invasive procedures may be used to reduce the chylous accumulation and allow the lymphatic system to develop or heal. Octreotide is the most frequently used drug in congenital chylothorax treatment. In the absence of somatostatin analogs, other medications, like sildenafil, have been used in several cases with success. We present a case of a late preterm infant who responded positively to oral sildenafil treatment. Conclusion. There is a considerable need for randomized studies to achieve standardized therapeutic algorithms.
AbstractThis chapter outlines a practical approach to the diagnosis and management of common human genetic conditions in patients who present with Congenital contractures. Based on the symptom, the user is shepherded through a step-by-step approach to a differential diagnosis. Prominent flow chart diagrams graphically depict the diagnostic approach. Recommended laboratory and/or imaging studies are concisely presented. Health supervision and management of the most common conditions associated with each presenting sign or symptom are suggested, where appropriate.
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.
