DeCure for Familial cold autoinflammatory syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial cold autoinflammatory 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 moduleFamilial cold autoinflammatory 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 familial cold autoinflammatory 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.
What the evidence adds up to
In a 2012 retrospective review of 34 Saudi children at a single rheumatology clinic, 8.8% were diagnosed with chronic infantile neurologic cutaneous and articular syndrome (CINCA), a cryopyrin-associated periodic syndrome. All CINCA patients in that cohort had a favourable response to anakinra. No patient in the entire cohort had amyloidosis. The referral diagnosis was inaccurate for every disease except familial Mediterranean fever, suggesting that rarer autoinflammatory conditions are frequently missed.
Familial cold autoinflammatory syndrome (FCAS) is genetically linked to Muckle-Wells syndrome (MWS). A 2002 study identified four distinct mutations of the CIAS1 gene on chromosome 1q44 in three FCAS families and one MWS family. The gene encodes a protein called cryopyrin. FCAS is characterised by skin rash (100% of patients), arthralgia (96%), fever (93%), conjunctivitis (84%), onset in the first six months of life (95%), an average delay of 2.5 hours between cold exposure and symptom onset, and an average episode duration of 12 hours. MWS leads to progressive sensorineural deafness, renal amyloidosis, fevers, chills, rigors, malaise, and chronic recurrent urticaria. Why mutations in the same gene produce two distinct clinical entities remains unexplained.
No controlled trial data for FCAS treatment are presented in these abstracts. The 2012 paediatric series reports anakinra response only for CINCA, not for FCAS specifically. The 2002 genetic study does not address treatment. A 2020 review article is cited but its content is not detailed in the provided abstracts.
What is still missing: prospective, controlled trials of interleukin-1 inhibitors specifically for FCAS; validated outcome measures for cold-provoked episodes; genetic and clinical stratification to explain why CIAS1 mutations cause FCAS in some families and MWS in others; and prospective data on long-term outcomes including amyloidosis risk in FCAS patients treated with targeted therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Saudi Medicine · 2012 · 13 citations · open access
A retrospective review of autoinflammatory diseases in Saudi children at a rheumatology clinic
AbstractBACKGROUND AND OBJECTIVE: Published data from Saudi Arabia regarding autoinflammatory diseases are scarce. In this study, we describe the clinical and laboratory features of autoinflammatory diseases in Saudi children. DESIGN AND SETTING: Restrospective, hospital-based study conducted from January 2010 until June 2010. PATIENTS AND METHODS: Patients with autoinflammatory disease treated at the Pediatric Rheumatology Clinic at King Faisal Specialist Hospital and Research Center, Riyadh, over the past 10 years were included. Autoinflammatory diseases included the following: familial Mediterranean fever (FMF); chronic recurrent multifocal osteomyelitis (CRMO); early-onset sarcoidosis (EOS); periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA); chronic infantile neurologic cutaneous and articular syndrome (CINCA); and Muckle-Wells syndrome (MWS). Demographic characteristics, diagnosis, age at onset, disease duration, follow-up duration, clinical and laboratory variables, and outcome data were compiled. Gathered laboratory data were part of patients' usual medical care. RESULTS: Thirty-four patients (females, 53%) with autoinflammatory diseases were included (mean age, 151 months). Mean disease duration was 118 months; mean age at onset was 32 months; consanguinity was present in 40%. Patients were diagnosed as follows: FMF, 50%; CRMO, 23.5%; CINCA, 8.8%; EOS, 8.8%; MWS, 6%; and PFAPA, 2.9%. The referral diagnosis was inaccurate in all patients except for FMF patients. Gene study was informative in 9 of 14 FMF patients who had molecular analyses. None of our cohort had amyloidosis. All CRMO patients had a favorable response to treatment except 1 patient, who had refractory, progressive disease. All patients with EOS had multiorgan involvement, including uveitis. All CINCA patients had a favorable response to anakinra. CONCLUSION: Our report shows that autoinflammatory diseases other than FMF may be overlooked. Increased awareness among pediatricians about these conditions will help to provide better health care to patients in the form of early diagnosis and management.
Mutation of a New Gene Encoding a Putative Pyrin-Like Protein Causes Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome
AbstractPurpose of the Study. To identify the genes for familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS).Study Population. Three families with FCAS and 1 family with MWS.Methods. Genomic DNA isolation, identification of coding region, DNA sequencing, and mutation detection. Protein prediction programs were also performed.Results. Four distinct mutations of the CIAS1 Gene on chromosome 1q44 were identified. The gene encodes a newly identified protein called cryopyrin.Conclusion. Mutations of the CIAS1 Gene encoding cryopyrin cause at least two distinct but similar cold-sensitive diseases, including FCAS and MWS.Reviewers’ Comments. This exciting discovery has led to the identification of a new protein, aptly named “cryopryin,” that links cold temperature exposure to inflammation. In this report, mutations of the cryopyrin gene were identified in family members with 2 rare autosomal dominant conditions that are “autoinflammatory” disorders (ie, conditions with recurrent inflammatory symptoms in the absence of autoantibodies): FCAS and MWS. Recently, FCAS—also known as familial cold urticaria and familial polymorphous cold eruption—has been well-described by the same authors. The FCAS clinical picture includes: skin rash (100%), arthralgia (96%), fever (93%), conjunctivitis (84%), disease onset in the first 6 months of life (95%), an average time delay between cold exposure and the onset of symptoms of 2.5 hours, and an average episode duration of 12 hours (Hoffman HM, et al. J Allergy Clin Immunol. 2001;108:615–620). In contrast, MWS leads to progressive sensorineural deafness, amyloidosis of the kidneys and other organs, fevers, chills, rigors, malaise, and chronic recurrent urticaria. The reason for the 2 distinct clinical entities associated with mutations in the same gene still need to be explored. For more discussion, see a brief editorial entitled “A fever gene comes in from the cold” by Kastner and O’Shea on pages 241–242 of the same issue.
Clinical pharmacology and therapy · 2020 · 4 citations · open access
Autoinflammatory diseases
AbstractAutoinflammatory diseases are a group of disorders caused by a dysregulation of the innate immune system. Unlike autoimmune diseases, they are not associated with changes in humoral or cellular immunity. The authors review the current classification, clinical manifestations and treatment of various systemic autoinflammatory diseases, including cryopirinassociated periodic syndrome, familial Mediterranean fever, HIDS, and TRAPS.
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.
