DeCure for Hereditary sensory and autonomic neuropathy
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for hereditary sensory and autonomic neuropathy — screening already-approved drugs against its 8-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 maps to a 8-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
approvedL-SerineApproved drug
Structures already discussed alongside hereditary sensory and autonomic neuropathy in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Structure of human glutamate carboxypeptidase II (GCPII) — L-Serine has a real, experimentally solved structure in complex with this target (PDB 2PVV, 2.11 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet osedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2PVV · 2.11 Å · ligand L-Serine (OSE). Experimental structure, not a prediction.
What the evidence adds up to
The hereditary sensory and autonomic neuropathies are a clinically and genetically heterogeneous group of disorders characterised by progressive axonal degeneration of sensory neurons, with autonomic features when those are a predominant part of the disease. By 2014, mutations in 12 genes had been identified — five for autosomal dominant forms and seven for autosomal recessive forms. The mode of inheritance can be either autosomal dominant or autosomal recessive. The identification of these genes has provided insights into pathogenesis, but no disease-modifying therapy is described in any of these reviews.
Diagnostic methods have progressed. By 2010, skin biopsies allowed diagnosis of small fibre sensory neuropathies, and genetic testing had defined new subtypes of inherited neuropathies with sensory involvement. Diagnostic criteria and guidelines had been developed for distal symmetric polyneuropathies, small fibre sensory neuropathies, and sensory neuronopathies. For some dysimmune sensory neuropathies or neuronopathies, intravenous immunoglobulin and tumour necrosis factor-alpha inhibitors showed promise, but these are acquired, not hereditary, forms. For the hereditary sensory and autonomic neuropathies themselves, no such treatment data are reported.
The reviews consistently note that much progress remains to be made regarding symptomatic and disease-modifying therapy. The 2004 review states that proper identification of genetic defects provides the opportunity for better genetic counselling and hopefully therapies in the future. The 2010 review concludes that much progress remains for a range of sensory neuropathies, including those from hereditary causes. The 2014 chapter states that gene identification is the basis for development of future therapies. No clinical trial results, response rates, survival data, or sample sizes for any drug in hereditary sensory and autonomic neuropathy are reported in any of these abstracts.
What is still missing is any clinical trial testing a specific drug in patients with hereditary sensory and autonomic neuropathy, any validated patient stratification beyond genetic subtype, and the funding needed to move from gene discovery to clinical testing.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2019 · 116 citations · open access
Randomized trial of <scp>l</scp> -serine in patients with hereditary sensory and autonomic neuropathy type 1
Abstract<h3>Objective</h3> To evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1). <h3>Methods</h3> In this randomized, placebo-controlled, parallel-group trial with open-label extension, patients aged 18–70 years with symptomatic HSAN1 were randomized to l-serine (400 mg/kg/day) or placebo for 1 year. All participants received l-serine during the second year. The primary outcome measure was the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS). Secondary outcomes included plasma sphingolipid levels, epidermal nerve fiber density, electrophysiologic measurements, patient-reported measures, and adverse events. <h3>Results</h3> Between August 2013 and April 2014, we enrolled and randomized 18 participants, 16 of whom completed the study. After 1 year, the l-serine group experienced improvement in CMTNS relative to the placebo group (−1.5 units, 95% CI −2.8 to −0.1, <i>p</i> = 0.03), with evidence of continued improvement in the second year of treatment (−0.77, 95% CI −1.67 to 0.13, <i>p</i> = 0.09). Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; <i>p</i> < 0.001). There were no serious adverse effects related to l-serine. <h3>Conclusion</h3> High-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression. <h3>Clinicaltrials.gov identifier</h3> NCT01733407. <h3>Classification of evidence</h3> This study provides Class I evidence that high-dose oral l-serine supplementation significantly slows disease progression in patients with HSAN1.
Hereditary Peripheral Neuropathies: Clinical Forms, Genetics, and Molecular Mechanisms
AbstractHereditary peripheral neuropathies, among the most common genetic disorders in humans, are a complex, clinically and genetically heterogeneous group of disorders that produce progressive deterioration of the peripheral nerves. This group of disorders includes hereditary neuropathy with liability to pressure palsies, Charcot-Marie-Tooth disease, Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy. Our understanding of these disorders has progressed from the description of the clinical phenotypes and delineation of the electrophysiologic and pathologic features to the identification of disease genes and elucidation of the underlying molecular mechanisms.
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.
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.
Oxford University Press eBooks · 2014 · 3 citations
Hereditary sensory and autonomic neuropathies
AbstractThe hereditary sensory neuropathies (HSN) discussed in this chapter are a clinically and genetically heterogeneous group of disorders that are characterized by exclusive or predominant axonal atrophy and degeneration of the sensory neurons. The term hereditary sensory and autonomic neuropathies (HSAN) is used when autonomic features represent a predominant feature of the disease. The classification of HSN/HSAN is based on the clinical presentation, the genetic background, and the age of disease onset. The mode of inheritance may be autosomal dominant or autosomal recessive. In the past two decades mutations in 12 genes have been indentified: five genes for autosomal dominant forms and seven genes for autosomal recessive forms. The identification of these genes has provided insights into the pathogenesis of HSN/HSAN and is the basis development of future therapies. This chapter reviews the known HSN/HSAN genes and their corresponding phenotypes.
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.
