DeCure for Neuropathy, hereditary sensory, type 2C
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for neuropathy, hereditary sensory, type 2C — 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 moduleNeuropathy, hereditary sensory, type 2C 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 neuropathy, hereditary sensory, type 2c 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
kinesin family member 1A (KIF1A) — KIF1A 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8UTS · 2.7 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary sensory neuropathy type 2C is one of a group of genetically determined peripheral neuropathies that feature prominent disturbance of peripheral sensory neurons. The condition is characterised by sensory loss, insensitivity to pain, and variable muscle weakness and wasting, with autonomic features also possible. Frequent complications include foot ulcerations and infections that can lead to osteomyelitis, necrosis, and amputations; these neuropathies have been termed ulceromutilating neuropathies. A 2004 review states that no curative treatment is available and current therapy is limited to symptom relief.
A 2010 review notes that diagnostic methods for both acquired and hereditary sensory neuropathies have progressed, leading to earlier and more specific diagnoses and a better understanding of disease mechanisms. However, the same review states that much progress remains to be made regarding symptomatic and disease-modifying therapy for a range of sensory neuropathies, including those from hereditary causes. Intravenous immunoglobulin and tumour necrosis factor-alpha inhibitors show promise for some dysimmune sensory neuropathies or neuronopathies, but these are not specific to hereditary sensory neuropathy type 2C.
A 1982 report describes three unrelated families with hereditary sensory and autonomic neuropathy type II (HSAN-II) caused by recessive mutations in the HSN2 gene on chromosome 12p13.33. Homozygous or compound heterozygous mutations resulted in truncation of the HSN2 protein. Genotype-phenotype correlations indicated that HSN2 mutations are associated with early childhood onset of a predominantly sensory neuropathy complicated by acromutilations in both upper and lower limbs.
What is still missing for hereditary sensory neuropathy type 2C specifically is any disease-modifying treatment tested in a controlled trial, any drug repurposing study with patient outcome data, and any identified molecular target that has been validated in human patients. The condition lacks both symptomatic and disease-modifying therapy, and no trial design or patient stratification strategy has been proposed for this subtype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 1983 · 213 citations
NOT ‘INDIFFERENCE TO PAIN’ BUT VARIETIES OF HEREDITARY SENSORY AND AUTONOMIC NEUROPATHY
AbstractThree children, from different kinships, with generalized insensitivity to pain, showed unusual manifestations of congenital, presumably inherited, sensory and autonomic neuropathy. The first child appeared to have a syndrome resembling those previously described as congenital indifference to pain, congenital universal loss of pain sensation from infancy without other apparent neurological deficit. Unlike most types of hereditary sensory and autonomic neuropathies (types I, II, III), but like type IV, she had normal sensory nerve action potentials. Abnormalities of sudomotor function and of somatosensory evoked potentials were demonstrated. A severe decrease in the number of sural nerve A delta fibres and a small reduction in C fibres were demonstrated morphometrically. An abnormality of C fibres was confirmed by a marked reduction in nerve dopamine-beta-hydroxylase activity. The plasma and CSF concentrations of beta endorphins, substance P and several other neuropeptides and hormones were normal. Unequivocal evidence of a neuropathic lesion is provided by this patient; her disorder may be identified as the fifth type of hereditary sensory and autonomic neuropathy. The second patient had a congenital pansensory neuropathy and progressive retinitis pigmentosa. Whether the disorder is inherited and, if so, whether the retinitis pigmentosa results from the same or from a second genetic abnormality, is unclear. The third case has, in addition to what is usually seen in hereditary sensory and autonomic neuropathy, type II, an unusually severe kinaesthetic difficulty in oral food handling. The sural nerves of the second and third patients had fibre composition characteristic of hereditary sensory and autonomic neuropathy, type II, few or no myelinated fibres and reduced numbers of unmyelinated fibres.
AbstractHereditary sensory neuropathies (HSNs) are a group of genetically determined peripheral neuropathies with prominent disturbance of the peripheral sensory neurons. They are characterized by sensory loss, insensitivity to pain, a variable degree of muscle weakness and wasting, as well as autonomic features. Frequent complications are foot ulcerations and infections that may lead to osteomyelitis, followed by necrosis and amputations. Consequently, the hereditary sensory neuropathies have also been termed ulceromutilating neuropathies. On the other hand, in the presence of additional motor weakness, they have been subclassified among the group of Charcot-Marie-Tooth (CMT) disorders. Sporadic and familial cases with different modes of inheritance are known to affect both children and adults. The most prevalent forms of the autosomal dominantly inherited hereditary sensory neuropathies are HSN I and CMT 2b. HSN I is associated with mutations in the SPTLC1 gene, whereas mutations in the RAB7 gene have been identified in CMT 2b. However, at least one more hitherto unknown gene responsible for autosomal-dominant hereditary sensory neuropathies must exist. Autosomal-recessive hereditary sensory neuropathies types III and IV, and probably also type V, result from mutations in the IKBKAP and NTRK1 genes. Very recently, the gene in HSN II (HSN2) has been identified. A spontaneous autosomal-recessive mutation in the Cct4 gene has been reported in the Sprague-Dawley rat strain with early onset sensory neuropathy. Although no curative treatment is available so far, and current therapy is limited to symptom relief, these molecular genetic advances in knowledge about the hereditary sensory neuropathies can be translated into clinical practice by improving diagnosis and genetic counseling. They will also be the basis for functional studies in the future.
Current Opinion in Neurology · 2010 · 16 citations
Sensory neuropathies, from symptoms to treatment
AbstractPURPOSE OF REVIEW: The present review focuses on recent developments in diagnosis and treatment of sensory neuropathies. It does not seek to establish a comprehensive classification of sensory neuropathies, nor treatment guidelines per se. RECENT FINDINGS: Diagnostic criteria and guidelines have been developed for distal symmetric polyneuropathies, small fiber sensory neuropathies and sensory neuronopathies. Novel diagnostic tools such as skin biopsies now allow diagnosis of small fiber sensory neuropathies. Genetic testing has defined new subtypes of mitochondrial neuropathies and inherited neuropathies with sensory involvement. Intravenous immunoglobulin and tumor necrosis factor-alpha inhibitors show promise for some dysimmune sensory neuropathies or neuronopathies. Additional options for management of neuropathic pain are emerging. SUMMARY: Diagnostic methods for both acquired and hereditary sensory neuropathies have progressed in recent years, leading to earlier and more specific diagnoses and a better understanding of disease mechanisms. Much progress remains to be made regarding symptomatic and disease-modifying therapy for a range of sensory neuropathies, including those due to diabetes, HIV infection and from dysimmune or hereditary causes.
Congenital sensory neuropathy: report of an atypical case
AbstractAn otherwise normal 11-year-old boy had reately reduced acral pain and temperature sensation with associated trophic damage. The disorder was present at birth, and there was no family history of similar problems. The patient also exhibited complete anhidrosis. The case may an "overlap" between what has been termed as hereditary sensory neuropathy (HSN) type 2 and type 4.
CONTINUUM Lifelong Learning in Neurology · 2023 · 6 citations
Hereditary Neuropathies
AbstractOBJECTIVE: This article provides an overview of hereditary neuropathies, describes the different hereditary neuropathy subtypes and the clinical approach to differentiating between them, and summarizes their clinical management. LATEST DEVELOPMENTS: Increasingly available clinical genetic testing has broadened the clinical spectrum of hereditary neuropathy subtypes and demonstrated a significant overlap of phenotypes associated with a single gene. New subtypes such as SORD -related neuropathy and CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome) have emerged. The optimization of clinical management has improved gait and motor function in the adult and pediatric populations. Novel therapeutic approaches are entering clinical trials. ESSENTIAL POINTS: Hereditary neuropathies constitute a spectrum of peripheral nerve disorders with variable degrees of motor and sensory symptoms, patterns of involvement, and clinical courses.
Archives of Pediatrics and Adolescent Medicine · 1986 · 3 citations
Paucifascicular Congenital Sensory Neuropathy in Identical Twins
AbstractA male infant had sensory and autonomic dysfunction, and his identical twin had a similar clinical finding. One twin was extensively studied, utilizing sural nerve, skin, and conjunctival biopsy specimens, to evaluate the status of peripheral sensory axons. The results support an antenatal neurodevelopmental disturbance in axonal growth that affects sensory neurons and limits their distal extension. Neuropathologic studies of this patient closely resemble findings in hereditary sensory neuropathy type II; clinically, however, this patient resembles patients with congenital autonomic dysfunction and universal pain loss. Investigation of proximal and distal sural nerve, skin, and/or conjunctival biopsy specimens is recommended in patients with sensory and autonomic dysfunction to help differentiate these patients to assist in genetic counselling, treatment, and prognosis. It is possible that clinical overlap in such patients may result from a common neuropathic process, but with varying degrees of involvement.
La Ley: Revista jurídica española de doctrina, jurisprudencia y bibliografía · 1982 · 0 citations
El abogado y el impuesto sobre la renta
AbstractHereditary sensory and autonomic neuropathy type II (HSAN-II) is caused by recessive mutations in the HSN2 gene assigned to chromosome 12p13.33. The authors report three unrelated HSAN-II families with homozygous or compound heterozygous mutations resulting in the truncation of the HSN2 protein. Genotype-phenotype correlations indicated that HSN2 mutations are associated with an early childhood onset of a predominantly sensory neuropathy, complicated by acromutilations in both upper and lower limbs.
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.
