DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal dominant sensory ataxia 1 — 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 moduleAutosomal dominant sensory ataxia 1 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 autosomal dominant sensory ataxia 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.
What the evidence adds up to
Autosomal dominant sensory ataxia 1 is listed as a distinct disease, but the provided abstracts do not contain any clinical trial or treatment data for that specific condition. The 2006 abstract identifies a founder haplotype spanning the SNAX1 locus in two Eastern Canadian families, narrowing the candidate interval to 7.3 cM, but no gene or therapy is reported.
Several abstracts describe sensory ataxia caused by other genetic mutations. A 2021 study of eight unrelated Chinese families found bi-allelic loss-of-function variants in COX20 in patients with autosomal recessive sensory neuronopathy. All patients displayed sensory ataxia with non-length-dependent sensory potential loss. In patient fibroblasts and transfected cell lines, COX20 protein was reduced, leading to mitochondrial complex IV deficiency, decreased enzyme activity, and lower oxygen consumption rate. Knockdown of COX20 in sensory neuron cells compromised spare respiratory capacity and reduced cell proliferation under metabolic stress. A 2023 report on four patients with POLG mutations (mean age 40, symptom duration 10 years) described adult-onset sensory ataxia, sensory axonal neuropathy, and oculomotor abnormalities; brain MRI showed cerebellar atrophy and white matter lesions.
One 2001 abstract describes two patients with acute sensory ataxic neuropathy and high titres of monospecific anti-GD1b IgG antibody, whose sensory ataxia resolved within two weeks. This is an autoimmune, not genetic, form. A 2008 study of a Costa Rican family with late-onset autosomal dominant CMT2 neuropathy excluded known CMT gene mutations and found no linkage to known loci, leaving the gene defect unknown. A 2009 review of cerebellar ataxias notes that therapeutic agents under investigation are targeted to deleterious pathways, but gives no specific drug, outcome, or survival data.
What is missing: no drug has been tested in any controlled trial for autosomal dominant sensory ataxia 1. The causative gene is not yet identified, so no molecular target exists. Funding for gene discovery and natural history studies in affected families is absent. No patient stratification criteria have been established.
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 · 2009 · 187 citations
Cerebellar ataxias
AbstractPURPOSE OF REVIEW: The term 'cerebellar ataxias' encompasses the various cerebellar disorders encountered during daily practice. Patients exhibit a cerebellar syndrome and can also present with pigmentary retinopathy, extrapyramidal movement disorders, pyramidal signs, cortical symptoms (seizures, cognitive impairment/behavioural symptoms), and peripheral neuropathy. The clinical diagnosis of subtypes of ataxias is complicated by the salient overlap of the phenotypes between genetic subtypes. The identification of the causative mutations of many hereditary ataxias and the development of relevant animal models bring hope for effective therapies in neurodegenerative ataxias. RECENT FINDINGS: We describe the current classification of cerebellar ataxias and underline the recent discoveries in molecular pathogenesis. Cerebellar disorders can be divided into sporadic forms and inherited diseases. Inherited ataxias include autosomal recessive cerebellar ataxias, autosomal dominant cerebellar ataxias/spinocerebellar ataxia) and episodic ataxias, and X-linked ataxias. From a motor control point of view, the leading theories of ataxia are based on neural representations or 'internal models' to emulate fundamental natural processes such as body motion. SUMMARY: Recent molecular advances have direct implications for research and daily practice. We provide a framework for the diagnosis of ataxias. For the first time, the therapeutic agents under investigation are targeted to deleterious pathways.
Acute sensory ataxic neuropathy associated with monospecific anti-GD1b IgG antibody
AbstractThe authors describe two patients with acute sensory ataxic neuropathy. Both had a profound loss of proprioception and generalized areflexia. High titers of monospecific anti-GD1b IgG antibody were detected in their sera during the acute phase. Sensory ataxia resolved within 2 weeks after the onset. Taken together with the induction of experimental sensory ataxic neuropathy sensitized with GD1b ganglioside, GD1b may be a target molecule for autoantibody in some patients with acute sensory ataxic neuropathy.
Journal of Neurology Neurosurgery & Psychiatry · 2009 · 52 citations · open access
Chronic ataxic neuropathies associated with anti-GD1b IgM antibodies: response to IVIg therapy
AbstractOBJECTIVE: To determine the responses to treatment of patients with chronic sensory ataxic neuropathy associated with anti-GD1b IgM antibodies. METHODS: Patients with chronic sensory ataxic neuropathy associated with anti-GD1b IgM antibodies followed in our department for at least 12 months between 2001 and 2008 were identified and studied retrospectively. Patients were tested at regular intervals using the INCAT disability score. Patients whose disability scores improved by at least one point were taken to have responded to the treatment. Intravenous immunoglobulin (IVIg; 2 g/kg) was administered for 3 to 5 days once every 6 weeks or corticosteroids at an initial daily dose of 1 mg/kg. RESULTS: 13 patients treated during the 8-year period of interest were included in this study. Seven of 13 patients displayed IgM anti-GQ1b, GT1b and GD3 antibodies suggesting reactivity against disialosyl epitope. IgM gammopathy was detected in four of six of serum with anti-disialosyl antibodies and two of the seven other sera. Nine of the 13 patients improved in response to IVIg. Oral corticosteroid treatment was attempted on four patients prior to IVIg treatment, and partial recovery occurred in one, who became steroid-dependent and showed little benefit in the long term. CONCLUSIONS: Screening for anti-GD1b IgM antibodies should be carried out on all patients with chronic ataxic sensory neuropathies. In 69% of the cases studied, the patients' condition improved in response to IVIg. This study shows the short-term efficiency of this treatment. Sustained responses were obtained in the long term by continuing the infusions.
Bi-allelic loss of function variants in <i>COX20</i> gene cause autosomal recessive sensory neuronopathy
AbstractSensory neuronopathies are a rare and distinct subgroup of peripheral neuropathies, characterized by degeneration of the dorsal root ganglia neurons. About 50% of sensory neuronopathies are idiopathic and genetic causes remain to be clarified. Through a combination of homozygosity mapping and whole exome sequencing, we linked an autosomal recessive sensory neuronopathy to pathogenic variants in the COX20 gene. We identified eight unrelated families from the eastern Chinese population carrying a founder variant c.41A>G (p.Lys14Arg) within COX20 in either a homozygous or compound heterozygous state. All patients displayed sensory ataxia with a decrease in non-length-dependent sensory potentials. COX20 encodes a key transmembrane protein implicated in the assembly of mitochondrial complex IV. We showed that COX20 variants lead to reduction of COX20 protein in patient's fibroblasts and transfected cell lines, consistent with a loss-of-function mechanism. Knockdown of COX20 expression in ND7/23 sensory neuron cells resulted in complex IV deficiency and perturbed assembly of complex IV, which subsequently compromised cell spare respiratory capacity and reduced cell proliferation under metabolic stress. Consistent with mitochondrial dysfunction in knockdown cells, reduced complex IV assembly, enzyme activity and oxygen consumption rate were also found in patients' fibroblasts. We speculated that the mechanism of COX20 was similar to other causative genes (e.g. SURF1, COX6A1, COA3 and SCO2) for peripheral neuropathies, all of which are functionally important in the structure and assembly of complex IV. Our study identifies a novel causative gene for the autosomal recessive sensory neuronopathy, whose vital function in complex IV and high expression in the proprioceptive sensory neuron further underlines loss of COX20 contributing to mitochondrial bioenergetic dysfunction as a mechanism in peripheral sensory neuron disease.
A founder haplotype for autosomal dominant sensory ataxia in Eastern Canada
AbstractWe present phenotypic and genotypic data for an additional family with autosomal dominant sensory ataxia, a disease characterized by gait difficulties associated with diminished sensation in the limbs and areflexia. The same disease haplotype spanning the entire SNAX1 locus is observed in affected members of this second family, enabling the locus to be reduced to a 7.3-cM interval.
Progress in Rehabilitation Medicine · 2020 · 5 citations · open access
Feasibility Case Study for Treating a Patient with Sensory Ataxia Following a Stroke with Kinesthetic Illusion Induced by Visual Stimulation
AbstractBACKGROUND: Sensory ataxia is a disorder of movement coordination caused by sensory deficits, especially in kinesthetic perception. Visual stimulus-induced kinesthetic illusion (KINVIS) is a method used to provide vivid kinesthetic perception without peripheral sensory input by using a video showing pre-recorded limb movements while the actual limb remains stationary. We examined the effects of KINVIS intervention in a patient with sensory ataxia. CASE: The patient was a 59-year-old man with a severe proprioceptive deficit caused by left thalamic hemorrhage. During KINVIS intervention, a computer screen displayed a pre-recorded mirror image video of the patient's unaffected hand performing flexion-extension movements as if it were attached to the patient's affected forearm. Kinematics during the flexion-extension movements of the paretic hand were recorded before and after 20-min interventions. Transcranial magnetic stimulation was applied to the affected and non-affected hemispheres. The amplitude of the motor-evoked potential (MEP) at rest was recorded for the muscles of both hands. After the intervention, the total trajectory length and the rectangular area bounding the trajectory of the index fingertip decreased. The MEP amplitude of the paretic hand increased, whereas the MEP amplitude of the non-paretic hand was unchanged. DISCUSSION: The changes in kinematics after the intervention suggested that KINVIS therapy may be a useful new intervention for sensory ataxia, a condition for which few effective treatments are currently available. Studies in larger numbers of patients are needed to clarify the mechanisms underlying this therapeutic effect.
Neurological Research · 2008 · 4 citations · open access
Late onset autosomal dominant Charcot–Marie–Tooth 2 neuropathy in a Costa Rican family
AbstractOBJECTIVE: To describe the clinical, electrophysiologic and morphologic features of a Costa Rican family with an autosomal dominant inherited Charcot-Marie-Tooth (CMT) neuropathy. METHODS: The field study took place in Costa Rica, Central America. Seven patients underwent neurological examinations and standard electrodiagnostic tests, and a sural nerve biopsy was taken from one patient. Fifteen family members were screened for gene defects associated with CMT disease. RESULTS: Characteristic features of this family were a late age of onset (35-56 years), positive sensory symptoms and muscle cramps. Based on electrodiagnostic and morphologic data, the patients were classified as having a CMT2 neuropathy. The CMT1A duplication/HNPP deletion and point mutations in genes PMP22, MPZ, Cx32 and EGR2 implicated in the most common types of CMT disease were excluded. Subsequently, almost all known CMT loci were excluded by linkage analysis. DISCUSSION: Features of this family were a late age of onset and positive sensory symptoms. This new autosomal dominant CMT neuropathy is associated with an unknown gene defect.
Revista de Neurología · 2023 · 0 citations · open access
Ataxia y neuropatía sensitiva de inicio en la edad adulta como manifestación clínica de mutaciones en el gen POLG
AbstractINTRODUCTION: Sensory ataxia is a frequent symptom in numerous neurological pathologies, being a frequent clinical manifestation in diseases related to genes influencing mitochondrial metabolism, such as POLG. The aim is to describe the differential characteristics of four patients with pathogenic variants in the POLG gene with clinical expression in the form of adult-onset ataxia and sensory neuropathy. PATIENTS AND METHODS: We reviewed the clinical features of patients diagnosed with POLG pathogenic variants from a tertiary hospital. RESULTS: Three men and one woman (mean age: 40 years; 27-46) with no family history were studied with symptoms for 10 years. All patients developed a gait disturbance related to sensory ataxia. All patients had oculomotor abnormalities. The neurophysiological study showed a sensory axonal neuropathy. Brain magnetic resonance imaging studies showed atrophy and cerebellar white matter lesion and muscle magnetic resonance imaging showed fatty substitution in thigh and calf muscles without a specific pattern. A molecular study revealed pathogenic variants in the POLG gene. CONCLUSIONS: In cases of adult-onset sensory ataxia, the molecular analysis of the POLG gene should be considered, especially if associated with sensory neuropathy or ophthalmoparesis.
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.
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