DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cold-induced sweating syndrome — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCold-induced sweating syndrome maps to a 3-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 cold-induced sweating 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
kelch like family member 7 (KLHL7) — KLHL7 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3II7 · 1.63 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Cold-induced sweating syndrome is a rare autosomal recessive disorder caused by mutations in the cytokine receptor-like factor 1 gene. A 30-year-old Japanese woman homozygous for a 23-base deletion of CRLF1 was followed longitudinally. In infancy she had feeding difficulty, hyperthermia, and facial features resembling Crisponi syndrome, but no paroxysmal muscular contractions. Profuse sweating began at age 3, and cold-induced sweating was recognised during elementary school. By adolescence she had developed a Marfanoid habitus with progressive kyphoscoliosis and characteristic craniofacial changes. The authors concluded that the longitudinal observation supports the notion that cold-induced sweating syndrome and Crisponi syndrome may be a single clinical entity with age-dependent expression.
An autonomic reflex screen in one case of cold-induced sweating syndrome type 1 with a CRLF1 mutation found normal Valsalva morphology, Valsalva ratio, and heart rate response to deep breathing for the patient's age. The quantitative sudomotor axon reflex test showed a non-length-dependent decrease in sweat volume. Tilt table testing revealed evidence of reflex vasovagal syncope, though the patient was asymptomatic without loss of consciousness.
A separate woman initially diagnosed with cold-induced sweating syndrome based on prominent cold-induced sweating and heat intolerance was later found to have Stüve-Wiedemann syndrome caused by a novel mutation in the leukemia inhibitory factor receptor gene. Exome sequencing excluded CRLF1 mutation. Skin biopsies from this patient provided the first human evidence of failed postnatal cholinergic differentiation of sympathetic neurons innervating sweat glands in cold-induced sweating, and of a neuropathy.
No controlled treatment trials for cold-induced sweating syndrome were identified in these abstracts. What is missing is any randomised trial of a pharmacological intervention, a standardised diagnostic protocol to distinguish cold-induced sweating syndrome from phenotypically overlapping disorders such as Stüve-Wiedemann syndrome, and systematic investigation of autonomic function in larger patient cohorts to clarify the underlying neuropathy.
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 Part A · 2010 · 15 citations
Cold‐induced sweating syndrome with neonatal features of Crisponi syndrome: Longitudinal observation of a patient homozygous for a <i>CRLF1</i> mutation
AbstractCold-induced sweating syndrome (CISS) is a rare autosomal recessive disorder caused by mutations in CRLF1 (cytokine receptor-like factor 1), characterized by profuse sweating in cold environmental temperature and craniofacial and skeletal features. Mutations in CRLF1 also cause Crisponi syndrome (CS), characterized by neonatal-onset paroxysmal muscular contractions as well as craniofacial and skeletal manifestations and abnormal functions of the autonomic nerve system. To date, it is an unresolved problem whether the two conditions are distinct clinical entities or a single clinical entity with variable expressions or with different presentations depending on the patients' age at diagnosis. We report on a 30-year-old Japanese woman with CISS and homozygous out-of-frame 23-base deletion of CRLF1. In infancy, she did not show paroxysmal muscular contractions, but showed feeding difficulty, hyperthermia, and facial characteristics including thick and arched eyebrows, a short nose with anteverted nostrils, full cheeks, an inverted upper lip, and a small mouth, resembling those observed in CS. Profuse sweating was noticed at 3 years of age. Cold-induced sweating was recognized in her elementary school days. In adolescence to adulthood, she showed a Marfanoid habitus with progressive kyphoscoliosis and craniofacial characteristics including dolichocephaly, a slender face with poor expression, a distinctive nose with hypoplastic nares, malar hypoplasia, prognathism, and a small mouth. This is the first report of detailed longitudinal observation of a patient with CRLF1 abnormalities, compatible with the notion that CISS and CS may be a single clinical entity.
Wilderness and Environmental Medicine · 2014 · 1 citations
A Randomized Controlled Trial of a Novel Application of Chemical Cold Packs for Treatment of Exercise-Induced Hyperthermia
AbstractFree accessAbstractFirst published online March 1, 2014A Randomized Controlled Trial of a Novel Application of Chemical Cold Packs for Treatment of Exercise-Induced HyperthermiaJohn Lissoway, MD, Grant S. Lipman, MD, […], Dennis A Grahn, PhD, Vinh H. Cao, Michael Shaheen, MD, Samson Phan, PhD, Eric A. Weiss, MD, and Craig H. Heller, PhD+5-5View all authors and affiliationsVolume 25, Issue 1https://doi.org/10.1016/j.wem.2013.12.022
Journal of Clinical Neuromuscular Disease · 2017 · 0 citations
Autonomic Reflex Screen Test Abnormalities in Cold-Induced Sweating Syndrome Type 1
AbstractCold-induced sweating syndrome (CISS) is a rare autosomal recessive disease due to mutation in the Cytokine receptor-like factor 1 (CRLF1). The characteristic symptom of CISS is the tendency to sweat profusely especially in the upper body and hands when the patient is exposed to cold temperature. We sought to first report the findings of autonomic reflex screen in a case of CISS type 1 with Cytokine receptor-like factor 1 mutation. Valsalva morphology, Valsalva ratio, and heart rate response to deep breathing were normal for the patient's age. Quantitative sudomotor axon reflex test showed nonlength dependent decrease in the sweat volume. Tilt table revealed evidence of reflex (vasovagal) "syncope," however, the patient was asymptomatic without loss of consciousness.
Annals of Clinical and Translational Neurology · 2005 · 0 citations
Edward Bond papers, 1945
AbstractA woman was isozygous for a novel mutation in the leukemia inhibitory factor receptor gene (LIFR) (c.2170C>G; p.Pro724Ala) which disrupts LIFR downstream signaling and results in Stüve-Wiedemann syndrome (STWS). She inherited two identical chromosomes 5 from her mother, heterozygous for the LIFR mutation. The presentation was typical for STWS, except there was no long bone dysplasia. Prominent cold-induced sweating and heat intolerance lead to an initial diagnosis of cold-induced sweating syndrome, excluded by exome sequencing. Skin biopsies provide the first human evidence of failed postnatal cholinergic differentiation of sympathetic neurons innervating sweat glands in cold-induced sweating, and of a neuropathy.
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.
