DeCure for Hereditary sensory and autonomic neuropathy type 1
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for hereditary sensory and autonomic neuropathy type 1 — screening already-approved drugs against its 5-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 1 maps to a 5-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 1 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
serine palmitoyltransferase long chain base subunit 1 (SPTLC1) — SPTLC1 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 vsddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7K0K · 2.6 Å · ligand 3-Dehydrosphinganine (VSD). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary sensory and autonomic neuropathy type 1 (HSAN-I) is an autosomal dominant, mainly sensory neuropathy that typically presents in the second and third decades with ulcerations and lancinating pain attacks. Diagnosis depends on genetic analysis of six genes: serine palmitoyltransferase long chain base subunits 1 and 2 (SPTLC1 and SPTLC2), atlastin 1 and 3 (ATL1 and ATL3), DNA methyltransferase 1, and Ras-related protein RAB7. Most patients carry SPTLC1 mutations that alter sphingolipid biosynthesis by modifying SPT substrate specificity, producing atypical neurotoxic deoxysphingoid bases (DSBs). Elevated DSBs have been found in plasma samples from patients and in mutant cells, making them a candidate biomarker of disease.
The hereditary sensory neuropathies as a group are clinically and genetically heterogeneous and less common than Charcot-Marie-Tooth disease. HSAN-I, which has minimal autonomic involvement and is more accurately termed hereditary sensory neuropathy type I, can present very similarly to Charcot-Marie-Tooth type 2B. In children, these neuropathies often manifest as painless injuries and can be misdiagnosed as leprosy. Two siblings have been reported with clinical, electrophysiological, and pathological evidence of HSAN.
Two cousins with differing clinical courses of hereditary sensory and autonomic neuropathy have been reported. One case was dominated by loss of sensation, autonomic crises, and pain. The other showed loss of sensation, mental retardation, and deafness, clinically similar to HSAN type II. Detailed molecular studies in the first case for all known associated genes were negative, but the occurrence of both cases within one kindred suggests a common genetic background, leading the authors to propose a Turkish variant of familial dysautonomia.
What is still missing is a clear understanding of the full genetic spectrum of HSAN-I, as demonstrated by cases with negative genetic testing for known genes. The biomarker potential of deoxysphingoid bases has not been validated in a prospective trial, and no disease-modifying therapy has been tested in a controlled setting. Patient stratification by specific SPTLC1 mutations or other genotypes remains an open problem, and funding for natural history studies and drug screening in cellular or animal models is limited.
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.
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.
Neurology Genetics · 2019 · 7 citations · open access
Deoxysphingolipids as candidate biomarkers for a novel <i>SPTLC1</i> mutation associated with HSAN-I
AbstractHereditary sensory and autonomic neuropathy type 1 (HSAN-I)—an autosomal dominant, mainly sensory neuropathy—typically affects patients in their second and third decades, presenting with ulcerations and lancinating pain attacks.1 Diagnosis is heavily dependent on genetic analysis, focusing on 6 genes: serine palmitoyltransferase ( SPT ) long chain base subunits 1 and 2 ( SPTLC1 and SPTLC2 ), atlastin 1 ( ATL1 ) and 3 ( ATL3 ), DNA methyltransferase 1, and Ras-related protein ( RAB7 ). Most patients carry SPTLC1 mutations (OMIM*605712) that affect sphingolipids biosynthesis by modifying SPT substrate specificity to produce atypical neurotoxic deoxysphingoid bases (DSBs). Along with their accumulation in mutant cells, elevated DSBs were also found in plasma samples, thus becoming a candidate biomarker of disease.2
Hereditary Sensory and Autonomic Neuropathy With Autonomic Crises
AbstractHereditary sensory and autonomic neuropathies have different phenotypes. We report 2 cousins with differing clinical courses of a hereditary sensory and autonomic neuropathy. The progressive disease in case 1 is dominated by loss of sensation, autonomic crises, and pain. Case 2 shows loss of sensation, mental retardation, and deafness, clinically similar to patients with hereditary sensory and autonomic neuropathy type II. Detailed molecular studies in case 1 for all known genes that are associated with hereditary sensory and autonomic neuropathies were negative. However, the occurrence of the 2 cases within 1 kindred makes a common genetic background likely. We, therefore, propose a Turkish variant of familial dysautonomia in these 2 patients.
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.
