DeCure for Hereditary sensory neuropathy-deafness-dementia syndrome
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for hereditary sensory neuropathy-deafness-dementia syndrome — screening already-approved drugs against its 4-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 neuropathy-deafness-dementia syndrome maps to a 4-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 neuropathy-deafness-dementia syndrome 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
Hereditary sensory neuropathy-deafness-dementia syndrome is not named in any of the provided abstracts. The abstracts describe related but distinct conditions. One 1976 report describes a case of radicular sensory neuropathy and deafness in a family where several members were similarly afflicted, fitting a pattern originally described by Hicks in 1922. Another 1976 report states that hereditary sensory neuropathy is an uncommon neurological disorder characterised by loss of pain and temperature sensation in the extremities, with nerve deafness as an associated feature. A 2023 follow-up of a 29-year-old man diagnosed with hereditary sensory and autonomic neuropathy type II notes that despite efforts to maintain an optimal quality of life, the lack of an early diagnosis led to an unfavourable prognosis and life condition.
A 2015 prospective study from a South Indian tertiary hospital found that among patients diagnosed with auditory neuropathy spectrum disorder, 60% had neurological involvement, including peripheral neuropathy, hereditary motor-sensory neuropathy, and spinocerebellar ataxia. Neurological lesions did not present simultaneously with hearing loss in most patients, and 66% of patients with auditory neuropathy spectrum disorder were born of consanguineous marriages. A 2019 review of inherited neuropathies notes that these are slowly progressive disorders affecting motor, sensory, and autonomic nerves, and that recent genetic advances have improved understanding of the underlying pathophysiology, providing a milieu for future development of disease-modifying therapies. A 2018 review of deaf-related genes states that hereditary deafness accounts for about 60% of deafness and can be divided into syndromic and non-syndromic forms.
No abstract provides any treatment data, survival statistics, or response rates for hereditary sensory neuropathy-deafness-dementia syndrome. What is missing is any clinical trial, any drug tested in this specific syndrome, any patient stratification by genotype, and any funding directed at this particular combination of symptoms.
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.
AbstractThe inherited neuropathies are a common and heterogeneous group of slowly progressive disorders affecting motor, sensory, and autonomic nerves. These hereditary conditions can be confined to the peripheral nervous system, termed the primary hereditary neuropathies, or can occur as part of a multisystem disease. Identification of systemic involvement is necessary to distinguish the primary and secondary hereditary neuropathies to prevent the misdiagnosis of potentially treatable entities. Recent genetic and technological advances have dramatically improved our understanding of the underlying pathophysiology of these inherited neuropathies and hence provide the correct milieu for the future development of disease-modifying therapies. This review provides clinical, neurophysiological, genetic, pathophysiological, and treatment insights into the primary inherited neuropathies, and those associated with multisystem diseases, including porphyria and mitochondrial disorders.
Annals of Indian Academy of Neurology · 2015 · 5 citations · open access
Neurological associations in auditory neuropathy spectrum disorder: Results from a tertiary hospital in South India
AbstractAIMS: To find out the prevalence and types of neurological abnormalities associated in auditory neuropathy spectrum disorder in a large tertiary referral center. SETTINGS AND DESIGN: A prospective clinical study was conducted on all patients diagnosed with auditory neuropathy spectrum disorder in the ear, nose, and throat (ENT) and neurology departments during a 17-month period. Patients with neurological abnormalities on history and examination were further assessed by a neurologist to determine the type of disorder present. RESULTS: The frequency of auditory neuropathy spectrum disorder was 1.12%. Sixty percent were found to have neurological involvement. This included cerebral palsy in children, peripheral neuropathy (PN), spinocerebellar ataxia, hereditary motor-sensory neuropathy, spastic paresis, and ponto-bulbar palsy. Neurological lesions did not present simultaneously with hearing loss in most patients. Sixty-six percent of patients with auditory neuropathy spectrum disorder were born of consanguineous marriages. CONCLUSIONS: There is a high prevalence of neurological lesions in auditory neuropathy spectrum disorder which has to be kept in mind while evaluating such patients. Follow-up and counselling regarding the appearance of neuropathies is therefore important in such patients. A hereditary etiology is indicated in a majority of cases of auditory neuropathy spectrum disorder.
Archives of Otolaryngology - Head and Neck Surgery · 1976 · 5 citations
Hereditary Deafness and Sensory Radicular Neuropathy
AbstractWe report a case of radicular sensory neuropathy and deafness. The patients appears to be one of a family in whom several members were similarly afflicted. Thus, this case fits the pattern of hereditary deafness and sensory radicular neuropathy, originally described by Hicks in 1922.
Clinical Case Reports · 2023 · 3 citations · open access
A rare case of hereditary sensory and autonomic neuropathy type II
AbstractWe describe the follow-up of a 29-year-old man diagnosed with hereditary sensory and autonomic neuropathy type II, including the different complications that presented since his childhood. Despite efforts to maintain an optimal quality of life, the lack of an early diagnosis led to an unfavorable prognosis and life condition.
Clinical and Experimental Dermatology · 1976 · 0 citations
Hereditary sensory neuropathy. REPORT OF A CASE*
AbstractA case of hereditary sensory neuropathy is reported and the condition is briefly discussed. Hereditary sensory neuropathy is an uncommon neurological disorder characterized by loss of pain and temperature sensation in the extremities. Neurotrophic complications are frequent and nerve deafness is an associated feature.
Int J Otolaryngol Head Neck Surg · 2018 · 0 citations
Update to common deaf-related genes in non-syndromic hearing impairment
AbstractDeafness is a common ear disease with sensorineural dysfunction. It is one of the most common causes of disability, which seriously affects the quality of human life. Hereditary deafness accounts for about 60% of deafness. Hereditary deafness can be divided into syndromic hearing impairmentus and non-syndromic hearing impairment. Syndromic hearing impairment is a hereditary syndrome in which deafness is associated with other clinical symptoms. Non-syndromic hearing impairment is a hereditary disease with single hearing loss as a clinical symptom. This article reviews the research progress of genetic genes in non-syndromic hearing impairment in order to explore the etiology and pathogenesis of deafness at molecular level.
Key words:
Deafness; Gene; non-syndromic hearing impairment
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.
