DeCure for Congenital insensitivity to pain-hypohidrosis syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital insensitivity to pain-hypohidrosis 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 moduleCongenital insensitivity to pain-hypohidrosis 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 congenital insensitivity to pain-hypohidrosis 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
PR/SET domain 12 (PRDM12) — PRDM12 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 3EP0 · 2.1 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Congenital insensitivity to pain with anhydrosis (CIPA), also called hereditary sensory and autonomic neuropathy type IV, is an autosomal recessive disorder. It is caused by a mutation in the neurotrophic receptor tyrosine kinase 1 gene, which encodes neurotrophic tyrosine kinase. Patients cannot feel pain in any part of the body, have anhidrosis, and often have mental retardation. Touch and pressure sensitivity are unimpaired. The condition is extraordinarily rare. A 2015 paper describes a 7-year-old female child with CIPA who presented with osteoarthritic neuropathy and was treated under general anaesthesia using a multidisciplinary team approach. A 2011 report covers a 5-year-old girl and a 2-year-old boy with CIPA, discussing clinical features and anaesthetic strategy. A 2019 paper describes anaesthetic management of two siblings, aged 17 and 14 years, with CIPA who had septic arthritis; sedation with midazolam alone provided satisfactory surgical comfort without causing haemodynamic instability.
Patients are frequently admitted to hospital with unrecognised traumatic fractures and unhealed wounds due to the lack of pain response. They may experience hyperthermia due to anhidrosis and sustain multiple fatal injuries. A 2024 paper, titled "Congenital Insensitivity to Pain: A Fatal Entity," highlights the potentially catastrophic effects of the condition in a 4-year-old girl and notes that all these factors contribute to early demise at a young age. The 2015 paper explicitly discusses the diagnostic and therapeutic dilemmas involved in treating these children.
No drug treatment for the underlying condition is described in any of these abstracts. The literature focuses entirely on clinical description, genetic aetiology, and anaesthetic management for surgery. What is missing is any trial of a disease-modifying therapy, any patient stratification beyond the known genetic subtypes, and the funding needed to develop such treatments for an extremely rare disorder.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Clinical Pediatric Dentistry · 2015 · 21 citations · open access
Congenital Insensitivity to Pain and Anhydrosis: Diagnostic and Therapeutic Dilemmas Revisited
AbstractFirst described in 1932 by Dearborn as 'congenital pure analgesia', congenital insensitivity to pain and anhydrosis (CIPA) or hereditary sensory and autonomic neuropathy (HSAN) type IV is an extremely rare autosomal recessive disorder. A 7-year-old female child who is an established case of congenital insensitivity to pain and anhydrosis visited the department of pediatric medicine with osteoarthritic neuropathy. A multidisciplinary team approach was utilized to treat the child under general anesthesia. This article also discusses the diagnostic and therapeutic dilemmas involved in treating this type of children. How to cite this article: Ravichandra KS, Kandregula CR, Koya S, Lakhotia D. Congenital Insensitivity to Pain and Anhydrosis: Diagnostic and Therapeutic Dilemmas revisited. Int J Clin Pediatr Dent 2015;8(1):75-81.
Ağrı - The Journal of The Turkish Society of Algology · 2019 · 1 citations · open access
Anaesthetic Management of Two Siblings with Congenital Pain Insensitivity Syndrome with Anhydrosis
AbstractCongenital insensitivity to pain with anhidrosis (CIPA) is a rare syndrome characterized by a lack of sensitivity to pain due to congenital sensory and autonomic neuropathies, anhidrosis, an inability to regulate body temperature, growth retardation, mental retardation at different levels of severity, and inadvertent self-harm. It is an autosomal recessive disorder that is result of a mutation in the neurotrophic receptor tyrosine kinase 1 gene, which encodes neurotrophic tyrosine kinase. CIPA patients are frequently admitted to hospitals with unrecognized traumatic fractures and unhealed wounds due to the lack of a pain response. Presently described is the method of anesthetic management used for 2 siblings, aged 17 and 14 years, with a generalized lack of pain, anhidrosis, mental retardation, and septic arthritis. Sedation with midazolam alone provided satisfactory surgical comfort without causing hemodynamic instability in these 2 patients with CIPA syndrome.
Indian Journal of Medical Specialities · 2024 · 0 citations · open access
Congenital Insensitivity to Pain: A Fatal Entity
AbstractAbstract Congenital insensitivity to pain (CIP), also known as congenital analgesia, is an autosomal recessive, extraordinarily rare condition, in which a patient cannot feel pain in any part of his or her body. These patients may experience hyperthermia due to anhidrosis and sustain multiple fatal injuries because they are unable to feel pain at all. All these contribute to the early demise of the patient at a young age. Herein, we attempt to highlight the potentially catastrophic effects of CIP in a 4-year-old girl and reevaluate the representative features that a prudent physician should be aware of.
Greater South Information System · 2011 · 0 citations · open access
Congenital insensitivity to pain with anhydrosis: report of a family case
AbstractCongenital Insensitivity to pain with anhydrosis (CIPA) is a rare inherited disease.It is classified as hereditary sensory and autonomic neuropathy type IV.Pain insensitivity and autonomic deficits are present, but touch and pressure sensitivity are unimpaired.Mental retardation is usually present.We report a family case of a 5 years old girl and 2 years old boy with congenital insensitivity to pain, while discussing the clinical features and the anesthetic strategy of such patients.Patients with Congenital Insensitivity to Pain with anhydrosis may undergo surgery because of susceptibility to trauma due to absence of pain.The clinical features may intrinsically possess anesthetic challenges.
DOAJ (DOAJ: Directory of Open Access Journals) · 2011 · 0 citations · open access
Congenital insensitivity to pain with anhydrosis: report of a family case
AbstractCongenital Insensitivity to pain with anhydrosis (CIPA) is a rare inherited disease. It is classified as hereditary sensory and autonomic neuropathy type IV. Pain insensitivity and autonomic deficits are present, but touch and pressure sensitivity are unimpaired. Mental retardation is usually present. We report a family case of a 5 years old girl and 2 years old boy with congenital insensitivity to pain, while discussing the clinical features and the anesthetic strategy of such patients. Patients with Congenital Insensitivity to Pain with anhydrosis may undergo surgery because of susceptibility to trauma due to absence of pain. The clinical features may intrinsically possess anesthetic challenges.
Oxford University Press eBooks · 2018 · 0 citations
Congenital insensitivity to pain
AbstractThe landmark paper discussed in this chapter is ‘Congenital insensitivity to pain. A clinical, genetic and neurophysiological study of four children from the same family’, published by D. C. Thrush in 1973. The study of patients with congenital conditions that result in pain insensitivity has been invaluable in helping define the molecular mechanisms of sensory processing. These patients share a major defining phenotype (they feel little or no pain from birth), although they often have differing subtle symptoms which belie a host of separate conditions that we have now started to recognize with the advent of molecular genetics (e.g. loss-of-function mutations in the gene encoding Nav1.7, and mutations related to nerve growth factor (NGF)); these include congenital insensitivity to pain with anhydrosis (CIPA; thought to be due to mutations in the gene encoding the NGF receptor NTRK1) and hereditary sensory and autonomic neuropathies (HSANs) such as familial dysautonomia.
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.
