DeCure for Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome — 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 moduleSpondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome 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 spondyloepimetaphyseal dysplasia-short limb-abnormal calcification 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
discoidin domain receptor tyrosine kinase 2 (DDR2) — DDR2 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 fluoranyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6FER · 2.87 Å · ligand 2-[4,5-bis(fluoranyl)-2-oxidanylidene-1'-(1~{H}-pyrazolo[3,4-b]pyridin-5-ylcarbonyl)spiro[indole-3,4'-piperidine]-1-yl]-~{N}-[2,2,2-tris(fluoranyl)ethyl]ethanamide (D6Q). Experimental structure, not a prediction.
What the evidence adds up to
Spondyloepimetaphyseal dysplasia short limb-abnormal calcification type (SMED-SL/AC) is a severe, autosomal recessive dwarfism syndrome characterised by progressive calcification of epiphyseal and other cartilaginous tissues. The most common cause of death is spinal cord damage secondary to atlantoaxial instability. The condition is clinically and radiographically apparent at birth or in early infancy, and a 1993 study of 8 patients (the oldest aged 4–5 years) concluded that almost all affected individuals come to medical attention within that age range. No survival rates or response data are reported in any of the abstracts.
The disorder is caused by pathogenic variants in the DDR2 gene, which encodes discoidin domain receptor tyrosine kinase 2. As of 2021, 37 cases and 8 pathogenic variants had been reported worldwide, mostly in individuals of Middle Eastern and Puerto Rican origin. A 2021 report on Turkish patients described 2 new cases (one with a novel missense variant p.S311G, one with a splice site variant c.2283+1G>A) and re-identified a previously reported truncating variant p.R489* in stored DNA from an earlier Turkish case, bringing the total number of molecularly confirmed Turkish patients to 4. The same report noted that Turkish patients appeared to have a more severe and early fatal course, and it expanded the clinical features of the disorder to include triventricular hydrocephalus, intracranial haemorrhage, hypopigmentation of hair, dry and scaly skin, arthralgia, and hypocalcaemia.
No drug treatment, clinical trial, or intervention of any kind is mentioned in any of the abstracts. There is no evidence that any therapy has been tested in these patients, and no data on response to any agent. The abstracts are limited to case descriptions, genetic findings, and radiographic diagnostic criteria.
What is missing is any preclinical or clinical work on drug repurposing, any animal model testing, any trial design, and any patient stratification beyond genetic variant type. Funding for natural history studies and for basic research into DDR2 signalling in cartilage calcification would be needed before any therapeutic hypothesis could be formulated.
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 · 1993 · 28 citations
Further delineation of spondylo‐meta‐epiphyseal dysplasia, short limb‐abnormal calcification type, with emphasis on diagnostic features
AbstractFurther delineation of a generalized bone dysplasia which we call spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type is presented. This dwarfing condition has several serious complications, with the most common cause of death being spinal cord damage secondary to atlantoaxial instability. It is a heritable condition with an autosomal recessive mode of transmission. Radiologic diagnostic criteria are developed on the basis of studies in 8 patients with the oldest being between 4 and 5 years old. The condition is clinically and radiographically apparent neonatally or in early infancy, and it is probable that all or almost all affected individuals will come to medical attention in the age range screened by this study.
Molecular Syndromology · 2021 · 3 citations · open access
Spondylometaepiphyseal Dysplasia Short Limb-Abnormal Calcification Type in Turkish Patients Reveals a Novel Mutation and New Features
AbstractSpondylometaepiphyseal dysplasia short limb-abnormal calcification type (SMED-SL/AC) is a rare autosomal recessive disorder. It is a severe dwarfism syndrome with a characteristic feature of progressive calcification of epiphyseal and other cartilaginous tissues. It is caused by pathogenic variants in the <i>DDR2</i> gene encoding the discoidin domain receptor tyrosine kinase 2. Thus far, 37 cases and 8 pathogenic variants have been reported. Most of the reported cases are of Middle Eastern and Puerto Rican origins. Only one Turkish case has been reported previously with a novel truncating variant p.(R489*). Here, we report 2 new cases, 1 with a novel variant p.(S311G) and 1 with a splice site variant c.2283+1G&#x3e;A. In addition, we reviewed a previously reported case, and sequencing of stored DNA revealed the recently reported nonsense variant p.(R489*) as the underlying cause. Therefore, our data increase the number of SMED-SL/AC Turkish patients with molecular results to 4. Furthermore, we compared the features of Turkish patients with other reported cases and expanded the characteristics of the disorder with new features such as triventricular hydrocephalus, intracranial hemorrhage, hypopigmentation of hair, dry and scaly skin, arthralgia, and hypocalcemia. We also compared the pathogenic variants of Turkish patients with other variants, aiming to explain the mechanism leading to a more severe and early fatal course in Turkish patients.
Supplementary Material for: Spondylometaepiphyseal Dysplasia Short Limb-Abnormal Calcification Type in Turkish Patients Reveals a Novel Mutation and New Features
AbstractSpondylometaepiphyseal dysplasia short limb-abnormal calcification type (SMED-SL/AC) is a rare autosomal recessive disorder. It is a severe dwarfism syndrome with a characteristic feature of progressive calcification of epiphyseal and other cartilaginous tissues. It is caused by pathogenic variants in the <i>DDR2</i> gene encoding the discoidin domain receptor tyrosine kinase 2. Thus far, 37 cases and 8 pathogenic variants have been reported. Most of the reported cases are of Middle Eastern and Puerto Rican origins. Only one Turkish case has been reported previously with a novel truncating variant p.(R489*). Here, we report 2 new cases, 1 with a novel variant p.(S311G) and 1 with a splice site variant c.2283+1G>A. In addition, we reviewed a previously reported case, and sequencing of stored DNA revealed the recently reported nonsense variant p.(R489*) as the underlying cause. Therefore, our data increase the number of SMED-SL/AC Turkish patients with molecular results to 4. Furthermore, we compared the features of Turkish patients with other reported cases and expanded the characteristics of the disorder with new features such as triventricular hydrocephalus, intracranial hemorrhage, hypopigmentation of hair, dry and scaly skin, arthralgia, and hypocalcemia. We also compared the pathogenic variants of Turkish patients with other variants, aiming to explain the mechanism leading to a more severe and early fatal course in Turkish patients.
Supplementary Material for: Spondylometaepiphyseal Dysplasia Short Limb-Abnormal Calcification Type in Turkish Patients Reveals a Novel Mutation and New Features
AbstractSpondylometaepiphyseal dysplasia short limb-abnormal calcification type (SMED-SL/AC) is a rare autosomal recessive disorder. It is a severe dwarfism syndrome with a characteristic feature of progressive calcification of epiphyseal and other cartilaginous tissues. It is caused by pathogenic variants in the <i>DDR2</i> gene encoding the discoidin domain receptor tyrosine kinase 2. Thus far, 37 cases and 8 pathogenic variants have been reported. Most of the reported cases are of Middle Eastern and Puerto Rican origins. Only one Turkish case has been reported previously with a novel truncating variant p.(R489*). Here, we report 2 new cases, 1 with a novel variant p.(S311G) and 1 with a splice site variant c.2283+1G>A. In addition, we reviewed a previously reported case, and sequencing of stored DNA revealed the recently reported nonsense variant p.(R489*) as the underlying cause. Therefore, our data increase the number of SMED-SL/AC Turkish patients with molecular results to 4. Furthermore, we compared the features of Turkish patients with other reported cases and expanded the characteristics of the disorder with new features such as triventricular hydrocephalus, intracranial hemorrhage, hypopigmentation of hair, dry and scaly skin, arthralgia, and hypocalcemia. We also compared the pathogenic variants of Turkish patients with other variants, aiming to explain the mechanism leading to a more severe and early fatal course in Turkish patients.
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.
