DeCure for Hereditary sensory and autonomic neuropathy type 5
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for hereditary sensory and autonomic neuropathy type 5 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary sensory and autonomic neuropathy type 5 maps to a 2-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 hereditary sensory and autonomic neuropathy type 5 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
nerve growth factor (NGF) — NGF 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 1WWW · 2.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary sensory and autonomic neuropathy type 5 is one of a group of rare genetically determined neuropathies. A 2004 review notes that the hereditary sensory and autonomic neuropathies are clinically and genetically heterogeneous and less common than Charcot-Marie-Tooth disease, but that major advances in identifying causative genes had occurred in the preceding decade. A 2006 report describes two siblings with the condition and warns of potential misdiagnosis with other sensory neuropathies, especially leprosy. A 2019 case report of a three-year-old boy with HSAN type 4, a related subtype, states plainly that no definitive treatment is available for that condition.
A 2001 report describes a Japanese family with a novel adult-onset form of hereditary sensory and autonomic neuropathy distinct from the five types classified by Dyck. Three of six siblings were affected, developing anosmia between ages 20 and 50, followed by anhidrosis and sensory loss. Skin ulceration was absent. Both superficial and deep sensation were impaired in the most distal parts of all four limbs, and all patients had orthostatic hypotension.
A 2016 functional analysis of NTRK1 missense mutations causing HSAN type IV studied seven patients and seven novel mutations. The analysis assessed TRKA glycosylation, cell membrane expression, nerve growth factor stimulated autophosphorylation, and neurite outgrowth. Results showed a diverse range of functional effects: one mutation appeared fully functional, another had partial activity in all assays, one affected only the PLCγ pathway, and four were null in all assays. The authors conclude that complete abolition of TRKA kinase activity is not the only pathogenic mechanism, and that assessing clinical pathogenicity requires a multifaceted approach.
What is still missing for HSAN type 5 specifically are large patient cohorts for natural history studies, validated outcome measures, and any clinical trial testing a targeted therapy. No drug treatment is mentioned in any of these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2004 · 73 citations
Hereditary sensory neuropathies
AbstractPURPOSE OF REVIEW: The hereditary sensory neuropathies, also known as the hereditary sensory and autonomic neuropathies, are a clinically and genetically heterogeneous group of disorders. As they are not as common as Charcot-Marie-Tooth disease, they do not receive the same level of attention, but there have been major advances in the identification of the causative genes in the past decade. Certain forms of hereditary sensory and autonomic neuropathy, especially hereditary sensory and autonomic neuropathy type I, which has minimal autonomic involvement and is more accurately termed hereditary sensory neuropathy type I, can present in a very similar fashion to certain forms of Charcot-Marie-Tooth disease (Charcot-Marie-Tooth type 2B, see below), and therefore it is important that clinicians who regularly manage patients with neuropathy are familiar with the latest developments in the hereditary sensory and autonomic neuropathies. This review will concentrate on the recent genetic advances in hereditary sensory and autonomic neuropathy, and especially on those forms that overlap clinically with Charcot-Marie-Tooth disease, hence the title of the review 'Hereditary sensory neuropathies' rather than hereditary sensory and autonomic neuropathies.
Charcot-Marie-Tooth Disease (Hereditary Motor Sensory Neuropathies) and Hereditary Sensory and Autonomic Neuropathies
AbstractBACKGROUND: Since the description of Charcot-Marie-Tooth disease over a century ago. it has now been recognized that these conditions are not caused by generalized metabolic defects but rather have various discrete genetic origins. These disorders can also have variable phenotypes due to dysfunction of peripheral nerve axons or their myelin due to the genetic defects that affect the formation of specific nerve proteins. REVIEW SUMMARY: This article summarizes the clinical presentation of various phenotypes of the hereditary motor sensory neuropathies and the hereditary sensory and autonomic neuropathies, genetic mutations, and their relevant protein products. Proper identification of the genetic defects provides the opportunity for better genetic counseling and hopefully therapies in the future.
Annals of Indian Academy of Neurology · 2006 · 8 citations · open access
Painless injuries in a child: Hereditary sensory and autonomic neuropathy
AbstractHereditary sensory autonomic neuropathies (HSAN) are rare genetically determined neuropathies. They often manifest as painless injuries in children and there is a potential for misdiagnosis with other sensory neuropathies especially leprosy. We report two siblings who clinically, electrophysiologically and pathologically have HSAN. We also summarise the current classification and recent genetic advances.
Apollo (University of Cambridge) · 2016 · 6 citations · open access
A Comprehensive Functional Analysis of NTRK1 Missense Mutations Causing Hereditary Sensory and Autonomic Neuropathy Type IV (HSAN IV).
AbstractHereditary sensory and autonomic neuropathy type IV (HSAN IV) is an autosomal recessive disorder characterized by a complete lack of pain perception and anhidrosis. Here, we studied a cohort of seven patients with HSAN IV and describe a comprehensive functional analysis of seven novel NTRK1 missense mutations, c.1550G >A, c.1565G >A, c.1970T >C, c.2096T >C, c.2254T >A, c.2288G >C, and c.2311C >T, corresponding to p.G517E, p.G522E, p.L657P, p.I699T, p.C752S, p.C763S, and p.R771C, all of which were predicted pathogenic by in silico analysis. The results allowed us to assess the pathogenicity of each mutation and to gain novel insights into tropomyosin receptor kinase A (TRKA) downstream signaling. Each mutation was systematically analyzed for TRKA glycosylation states, intracellular and cell membrane expression patterns, nerve growth factor stimulated TRKA autophosphorylation, TRKA-Y496 phosphorylation, PLCγ activity, and neurite outgrowth. We showed a diverse range of functional effects: one mutation appeared fully functional, another had partial activity in all assays, one mutation affected only the PLCγ pathway and four mutations were proved null in all assays. Thus, we conclude that complete abolition of TRKA kinase activity is not the only pathogenic mechanism underlying HSAN IV. By corollary, the assessment of the clinical pathogenicity of HSAN IV mutations is more complex than initially predicted and requires a multifaceted approach.
International Journal of Research in Medical Sciences · 2019 · 3 citations · open access
A case of hereditary sensory and autonomic neuropathy type 4 presenting with chronic trophic ulcers
AbstractHereditary Sensory and Autonomic Neuropathy (HSAN) is a rare group of diseases involving varying degrees of peripheral nervous system. It is classified into five main types. HSAN type 4 is associated with insensitivity to pain and temperature and anihidrosis. The method of this study was to authors present a case report of a 3 year-old boy with Hereditary Sensory and Autonomic Neuropathy Type 4 presenting with chronic ulcers. Conclusions of this study was to HSAN type IV is a rare condition. There is no definitive treatment available presently for this condition.
Adult-onset hereditary sensory and autonomic neuropathy accompanied by anosmia but without skin ulceration
AbstractWe report a novel type of hereditary sensory and autonomic neuropathy (HSAN) with adult onset in a Japanese family. One male and 2 females of 6 siblings were affected. They developed anosmia initially at the ages of 20-50 years, followed by anhidrosis and sensory loss. Skin ulceration was absent. Both superficial and deep sensation were impaired in the most distal parts of all 4 limbs. Orthostatic hypotension was present in all patients. This is a unique subtype of HSAN distinct from the HSAN I-V described by Dyck.
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.
