DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for multiple synostoses syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMultiple synostoses syndrome maps to a 2-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 multiple synostoses 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
growth differentiation factor 5 (GDF5) — GDF5 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 ipadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2BHK · 2.4 Å · ligand ISOPROPYL ALCOHOL (IPA). Experimental structure, not a prediction.
What the evidence adds up to
Multiple synostoses syndrome is a rare genetic condition characterised by progressive joint fusions beginning in the distal phalanges of the hands and feet and moving proximally to carpal, tarsal, radio-ulnar, and radio-humeral joints, as well as the spine. A single-institution cohort of 14 patients followed for a mean of 18.6 years from 1972 to 2017 found that all had tarsal synostoses, 9 had carpal synostoses, 7 had elbow fusions, and 2 had vertebral fusions. Facial dysmorphia was seen in 6 patients and 3 were hearing-impaired. A mutation in the NOG gene was found in 3 of the patients tested. Progressing joint fusions were invariably seen on x-rays among adults. Feet deformities had a severe impact on quality of life, and neurological complications secondary to spine fusions warranted at least one imaging study in childhood. The authors state there is no treatment for ankylosis and do not recommend physiotherapy, though surgical arthrodesis for pain may have reasonable outcomes.
A novel heterozygous missense variant in FGF9, c.566C > G, p.(Pro189Arg), has been reported in a case of multiple synostoses syndrome 3, an autosomal dominant disorder. Functional studies showed this variant impairs FGF9 homodimerisation but not FGFR3c binding. Only two other FGF9 variants in humans and one in mice had been described previously. The report notes additional features not described in earlier cases.
The broader literature on craniosynostosis, which involves premature suture fusion rather than the joint fusions of multiple synostoses syndrome, provides some context on reoperation rates. In a prospective study of 167 consecutive children with syndromic and nonsyndromic craniosynostosis followed for a mean of 2.8 years, reoperation equal to or exceeding the magnitude of the original procedure occurred in 7 percent of cases. Total reoperation rates were 27.3 percent for syndromic and 5.9 percent for nonsyndromic synostoses. Females and children with syndromic synostoses were more likely to require reoperation. Age at initial surgery, length of operation, and estimated blood loss did not predict a higher reoperation rate. An epidemiological study of single-suture synostoses from 1975 to 2004 found that metopic synostosis was increasing, with changing demographic bases and increasing proportions of syndromic patients.
What is still missing for multiple synostoses syndrome specifically is any drug therapy that alters the natural history of progressive joint fusion. The cohort data are retrospective and small, with no randomised trials. Patient stratification by genotype (NOG versus FGF9 mutations) is limited by the small number of genetically confirmed cases. Funding for natural history studies and for any preclinical work on molecular targets such as FGF9 homodimerisation or NOG signalling has not 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.
Plastic & Reconstructive Surgery · 2008 · 147 citations
The Changing Epidemiologic Spectrum of Single-Suture Synostoses
AbstractPURPOSE: Classic literature indicates an infrequency of metopic craniosynostosis (3 to 10 percent) compared to other single-suture craniosynostosis. Recent observation challenges these conceptions, warranting long-term demographic analysis. METHODS: Syndromic craniofacial dysostoses and multiple suture involvement were exclusion criteria, leaving only single suture synostoses treated between 1975 and 2004. A chart review was performed and patient information recorded. Chi square analysis and Fisher's exact were used to determine differences in patient characteristics. A Moran's I statistic was used to determine differences in spatial means and whether changes in incidence of single-suture synostoses over time are a function of regional phenomena. RESULTS: Over 800 patients presented to The Children's Hospital of Philadelphia with a diagnosis of single-suture synostosis. There was an outpacing of sagittal suture involvement over other sutures. Data demonstrate a decrease in unicoronal synostosis and an increase in metopic synostosis (p = 0.011). Geostatistical analysis reveals increasing separation between populations over the study period: 9.8 miles in the first 5 years to 20.8 miles in the last 5 years. Metopic maternal age increased between 1975-1989 and 1990-2004 (p = 0.002, 0.0002), while unicoronal maternal age did not. The proportion of male patients increased considerably in the metopic group compared to unicoronals from 1990-2004 (p = 0.0001), as did the proportion of syndromic metopic patients (p = 0.02). Plausible etiologies for these epidemiological shifts are discussed. CONCLUSIONS: Metopic synostosis is on the rise. Changing demographic bases and increasing proportions of syndromic patients may be clues to the etiology of this epidemiologic event.
Plastic & Reconstructive Surgery · 1997 · 88 citations
A Longitudinal, Statistical Study of Reoperation Rates in Craniosynostosis
AbstractA prospective, statistical study of reoperation rates was done in the treatment of 167 consecutive children with nonsyndromic and syndromic craniosynostosis over a 6-year period at Scottish Rite Children's Medical Center in Atlanta, Georgia. Mean length of follow-up was 2.8 years, with a range of 3 months to 6 years. Reoperation equal to or exceeding the magnitude of the original procedure occurred in 7 percent of cases. Multiple regression analysis revealed several factors associated with reoperation: Females and children with syndromic synostoses were more likely to require reoperation. Total reoperation rates for syndromic and nonsyndromic synostoses were 27.3 and 5.9 percent, respectively. Age at initial surgery, length of operation, and estimated blood loss did not predict a higher reoperation rate.
American Journal of Medical Genetics · 1984 · 21 citations
Multiple synostosis syndrome: Study of a large Brazilian kindred
AbstractWe report a large Brazilian kindred with 28 cases of the autosomal dominant multiple synostosis syndrome. The main anomalies were symphalangism and carpal and tarsal synostoses. Other common findings included synostosis involving other bones, absence of phalanges and nails, short metacarpals, pes planovalgus with prominent lateral border, hypoplastic alae of nose, short upper lip, and dermatoglyphic abnormalities. This may be a variant of the WL syndrome.
Clinical Genetics · 2020 · 8 citations · open access
A novel heterozygous variant in <scp> <i>FGF9</i> </scp> associated with previously unreported features of multiple synostosis syndrome 3
AbstractHuman multiple synostoses syndrome 3 is an autosomal dominant disorder caused by pathogenic variants in FGF9. Only two variants have been described in FGF9 in humans so far, and one in mice. Here we report a novel missense variant c.566C > G, p.(Pro189Arg) in FGF9. Functional studies showed this variant impairs FGF9 homodimerization, but not FGFR3c binding. We also review the findings of cases reported previously and report on additional features not described previously.
Journal of Pediatric Rehabilitation Medicine · 2021 · 0 citations
Multiple synostoses syndrome: Radiological findings and orthopedic management in a single institution cohort
AbstractPURPOSE: Multiple synostoses syndrome (MSS) is a rare genetic condition. Classical features consist of joint fusions which notably start at the distal phalanx of the hands and feet with symphalangism progressing proximally to carpal, tarsal, radio-ulnar, and radio-humeral joints, as well as the spine. Usually, genetic testing reveals a mutation of the NOG gene with variable expressivity. The goal was to present the anatomical, functional, and radiological presentations of MSS in a series of patients followed since childhood. METHODS: Patients with more than 3 synostoses affecting at least one hand joint were included. When possible, genetic screening was offered. RESULTS: A retrospective study was performed from 1972 to 2017 and included 14 patients with a mean follow-up of 18.6 years. Mutation of the NOG protein coding gene was seen in 3 patients. All presented with tarsal synostoses including 9 carpal, 7 elbow, and 2 vertebral fusions. Facial dysmorphia was seen in 6 patients and 3 were hearing-impaired. Surgical treatment of tarsal synostosis was performed in 4 patients. Progressing joint fusions were invariably seen on x-rays amongst adults. CONCLUSION: Long radiological follow-up allowed the assessment of MSS progression. Feet deformities resulted in a severe impact on quality of life, and neurological complications secondary to spine fusions warranted performing at least one imaging study in childhood. As there is no treatment of ankylosis, physiotherapy is not recommended. However, surgical arthrodesis for the treatment of pain may have reasonable outcomes.
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.
