DeCure for Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAtaxia, early-onset, with oculomotor apraxia and hypoalbuminemia maps to a 3-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 ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia 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
aprataxin (APTX) — APTX 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 ampdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4NDH · 1.848 Å · ligand ADENOSINE MONOPHOSPHATE (AMP). Experimental structure, not a prediction.
What the evidence adds up to
Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease caused by SETX mutations. In a 2008 study of 7 patients from 4 unrelated families, onset ranged from 13 to 18 years with progressive cerebellar ataxia and areflexia. Oculomotor apraxia was detected in only 1 of the 7 patients. All 4 patients tested had predominant axonal neuropathy and diffuse cerebellar atrophy on imaging. All 7 patients had elevated alpha-fetoprotein (AFP) serum levels, and 5 of 8 nonsymptomatic heterozygous relatives also had moderately increased AFP. Three novel SETX mutations were found.
A 2014 report described 3 video cases that expanded the clinical spectrum of AOA2. One patient had a novel mutation with cervical dystonia as the first symptom, absence of neuropathy, and disease onset beyond age 40. Oculographic analysis revealed distinct patterns of oculomotor abnormalities in all 3 patients, suggesting oculography might detect subclinical oculomotor apraxia. The authors noted the clinical spectrum of AOA2 might be broader than previously described in larger series.
Ataxia with oculomotor apraxia type 1 (AOA1) is a separate autosomal recessive disorder caused by APTX mutations. A 2022 case report described a 14-year-old Chinese boy who developed ataxia with staggering gait from age 4. He presented with early-onset cerebellar ataxia, peripheral axonal neuropathy, cognitive impairment, hypoalbuminemia, and hypercholesterolemia, but without oculomotor apraxia. Whole-exome sequencing identified a compound heterozygous mutation in APTX (c.739C>T and c.501dupG), the latter being a novel mutation. This was the first genetically confirmed AOA1 patient in a Chinese family.
What remains missing are treatments or interventions tested in any of these patients. No drug, supplement, or therapeutic trial is mentioned in any of the abstracts. The natural history and genetic heterogeneity are better described, but no clinical trial data exist for either AOA1 or AOA2. Patient stratification by mutation type, age of onset, or presence of oculomotor apraxia has not been used to guide any prospective study. Funding for natural history studies and for any drug-repurposing screen in cellular or animal models of these diseases is absent from the published record.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Neurology · 2008 · 48 citations
Clinical and Molecular Findings of Ataxia With Oculomotor Apraxia Type 2 in 4 Families
AbstractBACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease caused by SETX mutations in 9q34 resulting in cerebellar ataxia in association with peripheral neuropathy, cerebellar atrophy on imaging, an elevated alpha-fetoprotein (AFP) serum level, and occasional oculomotor apraxia. OBJECTIVE: To describe the clinical and molecular findings of 7 patients with a clinical presentation of AOA2 and their relatives. DESIGN: Case report. SETTING: Projet Hospitalier de Recherche Clinique. PATIENTS: Seven patients with AOA2 and their family members. INTERVENTION: Linkage analysis and direct sequencing of all exons of SETX were performed in all patients. Magnetic resonance imaging and electroneuromyography were performed and the patients' AFP serum levels were tested. RESULTS: We identified 7 patients with AOA2 from 4 unrelated families. Three novel SETX mutations were found. The clinical picture of the patients reported is fairly homogeneous and in accordance with the classic AOA2 presentation: onset from 13 to 18 years of progressive cerebellar ataxia and areflexia. Oculomotor apraxia was detected in 1 patient. Predominant axonal neuropathy and a diffuse cerebellar atrophy were found in the 4 patients tested. All patients had elevated AFP serum levels and 5 of 8 nonsymptomatic heterozygous relatives had moderately increased AFP serum levels as well. CONCLUSIONS: Ataxia with oculomotor apraxia type 2 is a homogeneous form of cerebellar ataxia with occasional oculomotor apraxia. Most nonsymptomatic heterozygous carriers present with increased AFP serum levels.
Movement Disorders Clinical Practice · 2014 · 9 citations · open access
The Clinical Spectrum of Ataxia with Oculomotor Apraxia Type 2
AbstractAtaxia with oculomotor apraxia type 2 (AOA2) is an inherited disorder caused by mutations within both alleles of the senataxin gene. First symptoms are usually recognized before the age of 30. Unlike several other autosomal recessive cerebellar ataxia syndromes, levels of alpha-fetoprotein are nearly always elevated in AOA2 and thus narrowing down the differential diagnosis list. We present 3 video cases illustrating and expanding the clinical spectrum of AOA2, with 1 case bearing a novel mutation with cervical dystonia as the first symptom, the absence of neuropathy, and a disease onset beyond the age of 40. Furthermore, all patients were assessed by oculographic analysis, which revealed distinct patterns of oculomotor abnormalities. The clinical spectrum of AOA2 might be even broader than previously described in larger series. Oculography might be a useful tool to detect subclinical oculomotor apraxia in this disorder.
Frontiers in Neurology · 2022 · 1 citations · open access
Case report: A novel APTX p.Ser168GlufsTer19 mutation in a Chinese family with ataxia with oculomotor apraxia type 1
AbstractAtaxia with oculomotor apraxia type 1 (AOA1) is a rare genetic disorder and is inherited in an autosomal recessive manner. It is mainly characterized by childhood-onset progressive cerebellar ataxia, with dysarthria and gait disturbance being the two most common and typical manifestations. Axonal sensorimotor peripheral neuropathy, dystonia, chorea, and cognitive impairment are common associated symptoms, as are hypoalbuminemia and hypercholesterolemia. Oculomotor apraxia (OMA)has been reported to be a feature often, although not exclusively, associated with AOA1. The Aprataxin gene, APTX , is ubiquitously expressed, and numerous APTX mutations are associated with different clinical phenotypes have been found. In the present study, we enrolled a 14-year-old boy who developed ataxia with staggering gait from the age of 4 years. Early-onset cerebellar ataxia, peripheral axonal neuropathy, cognitive impairment and hypoalbuminemia, hypercholesterolemia were presented in this patient, except for OMA. We applied ataxia-related genes filtering strategies and whole-exome sequencing (WES) to discover the genetic factors in a Chinese family. Sanger sequencing was used in the co segregation analysis in the family members. A compound heterozygous mutation in APTX gene (c.739C>T and c.501dupG) was identified. This is the first description of a genetically confirmed patient of AOA1 in a Chinese family in addition to a novel mutation of c.501dupG in APTX.
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.
