DeCure for Congenital insensitivity to pain syndrome, Marsili type
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital insensitivity to pain syndrome, Marsili type — 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 syndrome, Marsili type 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 syndrome, marsili type 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
Congenital insensitivity to pain (CIP) is a group of rare autosomal recessive disorders defined by the absence of pain sensation from birth. The underlying genetics are heterogeneous. Loss-of-function mutations in the SCN9A gene, which encodes the Nav1.7 sodium channel, are a known cause. A 2014 case report identified a novel homozygous G2755T mutation in exon 15 of SCN9A in a patient with CIP; that patient also had abnormal electrophysiological studies, which the authors attributed to secondary spinal disease and Charcot joints rather than to the primary neuropathy. A 2024 study of two Thai patients with CIP, self-mutilation, acro-osteolysis, corneal scars, reduced temperature sensation, and dental anomalies found a rare homozygous variant c.4039C>T (p.Arg1347Cys) in the plakin domain of the Plec gene. Skin biopsies showed fewer axons, decreased vimentin, and absent neurofilament expression, indicating a lack of dermal nerves. This is the first report linking a Plec variant to CIP in humans.
Earlier clinical descriptions confirm the natural history. A 2002 report of five patients from four related Saudi families, aged 10 months to 23 years, documented lifelong pain insensitivity with normal other sensory modalities. All had sustained multiple painless fractures and disfigurement but were otherwise neurologically normal. A 2018 review notes that CIP patients share the major phenotype of little or no pain from birth but often have differing subtle symptoms, reflecting separate conditions now distinguished by molecular genetics: congenital insensitivity to pain with anhidrosis (CIPA) is linked to mutations in NTRK1, the nerve growth factor receptor, and hereditary sensory and autonomic neuropathies (HSANs) include familial dysautonomia.
Current treatment is symptomatic only. A 2023 review states that the first targeted therapies are being tested, but no efficacy data from those trials are reported in these abstracts. The same review notes that research into CIP may inform understanding of chronic pain, but this remains speculative. What is still missing: any completed or published trial of a targeted therapy for CIP, a clear stratification of patients by genotype (SCN9A, NTRK1, Plec, and others) to guide trial design, and the funding needed to move from single-case genetic reports to interventional studies with meaningful endpoints such as fracture reduction or wound healing.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Case Reports in Neurological Medicine · 2014 · 21 citations · open access
Congenital Insensitivity to Pain: A Case Report and Review of the Literature
AbstractCongenital insensitivity to pain (CIP) is a rare autosomal recessive genetic disease caused by mutations in the SCN9A gene. We report a patient with the clinical features consistent with CIP in whom we detected a novel homozygous G2755T mutation in exon 15 of this gene. Routine electrophysiological studies are typically normal in patients with CIP. In our patient, these studies were abnormal and could represent the consequences of secondary complications of cervical and lumbosacral spine disease and associated severe Charcot's joints.
Congenital Insensitivity to Pain in Four Related Saudi Families
AbstractCongenital insensitivity to pain (hereditary sensory and autonomic neuropathy [HSAN] type V) is a rare disorder of pain perception in which pain sensation is absent from birth, with no other neurologic deficits. We report five Saudi patients (three male and two female) age 10 months to 23 years who lacked pain sensation from birth but have normal appreciation of other sensory modalities. They are from four related families who are descended from one grandfather. The patients had sustained many painless injuries resulting in fractures and disfigurement, but otherwise are completely normal.
Highlights in Science Engineering and Technology · 2023 · 0 citations · open access
Congenital insensitivity to pain: the controversy and possible pathophysiology model in progress
AbstractCongenital insensitivity to pain (CIP) is a disorder that emphasizes the critical role of nociception in protecting against tissue damage and is characterized by repeated injuries, burns, and poor wound healing. CIP is a developmental defect caused by pathogenic genetic variants in multiple genes. Current treatment modalities for patients with CIP are primarily symptomatic, but the first targeted therapies are being tested. Interestingly, this area of research offers new ideas for slow-moving pain, one of the great challenges still unresolved by the medical community.
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.
International Journal of Molecular Sciences · 2024 · 0 citations · open access
Homozygosity for a Rare Plec Variant Suggests a Contributory Role in Congenital Insensitivity to Pain
AbstractCongenital insensitivity to pain is a rare human condition in which affected individuals do not experience pain throughout their lives. This study aimed to identify the molecular etiology of congenital insensitivity to pain in two Thai patients. Clinical, radiographic, histopathologic, immunohistochemical, and molecular studies were performed. Patients were found to have congenital insensitivity to pain, self-mutilation, acro-osteolysis, cornea scars, reduced temperature sensation, tooth agenesis, root maldevelopment, and underdeveloped maxilla and mandible. The skin biopsies revealed fewer axons, decreased vimentin expression, and absent neurofilament expression, indicating lack of dermal nerves. Whole exome and Sanger sequencing identified a rare homozygous variant c.4039C>T; p.Arg1347Cys in the plakin domain of Plec, a cytolinker protein. This p.Arg1347Cys variant is in the spectrin repeat 9 region of the plakin domain, a region not previously found to harbor pathogenic missense variants in other plectinopathies. The substitution with a cysteine is expected to decrease the stability of the spectrin repeat 9 unit of the plakin domain. Whole mount in situ hybridization and an immunohistochemical study suggested that Plec is important for the development of maxilla and mandible, cornea, and distal phalanges. Additionally, the presence of dental anomalies in these patients further supports the potential involvement of Plec in tooth development. This is the first report showing the association between the Plec variant and congenital insensitivity to pain in humans.
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.
