DeCure for Familial cold autoinflammatory syndrome 3
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial cold autoinflammatory syndrome 3 — 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 3 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 3 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
phospholipase C gamma 2 (PLCG2) — PLCG2 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 gspdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2W2X · 2.3 Å · ligand 5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE (GSP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2024 retrospective study of 334 patients with suspected autoinflammatory disease at a single adult reference centre, 134 (40%) were initially diagnosed with undifferentiated disease. Of those, 44 (32.8%) met criteria for adult PFAPA syndrome. The remaining patients were grouped into four phenotypes: predominantly fever (18 patients), predominantly abdominal/pleuritic pain (9 patients), predominantly pericarditis (18 patients), and complex syndrome (45 patients). Complete response rates were 41.3% for prednisone, 40.2% for colchicine, and 58.3% for anakinra across the whole undifferentiated group. In the complex syndrome subgroup, complete responses fell to 21.9% with prednisone, 25.7% with colchicine, and 44.4% with anakinra; this subgroup most often required additional immunosuppressive drugs.
Familial cold autoinflammatory syndrome 3 is caused by mutations in the CIAS1 gene on chromosome 1q44, which encodes the protein cryopyrin. A 2002 study identified four distinct mutations in three families with FCAS and one family with Muckle-Wells syndrome. The FCAS clinical picture includes skin rash (100% of patients), arthralgia (96%), fever (93%), conjunctivitis (84%), disease 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. Muckle-Wells syndrome leads to progressive sensorineural deafness, renal amyloidosis, fevers, chills, rigors, malaise, and chronic recurrent urticaria. The reason two distinct clinical entities arise from mutations in the same gene remains unexplained.
A 2011 review describes systemic autoinflammatory diseases as inherited disorders of innate immunity characterised by recurrent febrile attacks lasting hours to weeks, with multi-district inflammation of skin, serosal membranes, joints, gastrointestinal tract, and central nervous system. The group includes cryopyrin-associated periodic syndromes, familial Mediterranean fever, mevalonate kinase deficiency syndrome, tumour necrosis factor receptor-associated periodic syndrome, and hereditary pyogenic and granulomatous disorders. Diagnosis combines clinical and biohumoral data, sometimes confirmed by genotype analysis.
What is still missing: prospective trials comparing anakinra, colchicine, and prednisone specifically in genetically confirmed FCAS3 patients; data on long-term outcomes such as amyloidosis prevention; and patient stratification by specific CIAS1 mutation to explain the phenotypic variability between FCAS and Muckle-Wells syndrome.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Autoimmunity Reviews · 2024 · 13 citations · open access
Disease phenotypes in adult patients with suspected undifferentiated autoinflammatory diseases and PFAPA syndrome: Clinical and therapeutic implications
AbstractBACKGROUND: Undifferentiated autoinflammatory diseases are characterized by recurrent or persistent fever, usually combined with other inflammatory manifestations, and negative or inconclusive genetic studies for monogenic autoinflammatory disorders. AIMS: To define and characterize disease phenotypes in adult patients diagnosed in an adult reference center with undifferentiated autoinflammatory diseases, and to analyze the efficacy of the drugs used in order to provide practical diagnostic and therapeutic recommendations. METHODS: Retrospective study (2015-2022) of patients with undifferentiated autoinflammatory diseases among all patients visited in our reference center. Demographic, clinical, laboratory features and detailed therapeutic information was collected. RESULTS: Of the 334 patients with a suspected autoinflammatory disease, 134 (40%) patients (61% women) were initially diagnosed with undifferentiated autoinflammatory diseases. Mean age at disease onset and at diagnosis was 28.7 and 37.7 years, respectively. In 90 (67.2%) patients, symptoms started during adulthood. Forty-four (32.8%) patients met diagnostic/classification criteria for adult periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome. In the remaining patients, four additional phenotypes were differentiated according to the predominant manifestations: a) Predominantly fever phenotype (n = 18; 13.4%); b) Predominantly abdominal/pleuritic pain phenotype (n = 9; 6.7%); c) Predominantly pericarditis phenotype (n = 18; 13.4%), and d) Complex syndrome phenotype (n = 45; 33.6%). Prednisone (mainly on demand), colchicine and anakinra were the drugs commonly used. Overall, complete responses were achieved with prednisone in 41.3%, colchicine in 40.2%, and anakinra in 58.3% of patients in whom they were used. By phenotypes, prednisone on demand was more effective in adult PFAPA syndrome and colchicine in patients with the abdominal/pleuritic pain pattern and PFAPA syndrome. Patients with complex syndrome achieved complete responses with prednisone (21.9%), colchicine (25.7%) and anakinra (44.4%), and were the group more often requiring additional immunosuppressive drugs. CONCLUSIONS: The analysis of the largest single-center series of adult patients with undifferentiated autoinflammatory diseases identified and characterized different disease phenotypes and their therapeutic approaches. This study is expected to contribute to increase the awareness of physicians for an early identification of these conditions, and to provide the best known therapeutic options.
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.
The laboratory approach in the diagnosis of systemic autoinflammatory diseases
AbstractSystemic autoinflammatory diseases are a group of inherited disorders of the innate immunity characterized by the recurrence of febrile attacks lasting from few hours to few weeks and multi-district inflammation of different severity involving skin, serosal membranes, joints, gastrointestinal tube and central nervous system. The vast majority of these conditions is caused by mutations in genes involved in the control of inflammation and apoptosis mechanisms. The group includes familial Mediterranean fever, mevalonate kinase deficiency syndrome, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin-associated periodic syndromes, hereditary pyogenic and granulomatous disorders. Their diagnostic identification derives from the combination of clinical and biohumoral data, though can be sometimes confirmed by genotype analysis.
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.
