DeCure for Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEarly-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome maps to a 2-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 early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome 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
ubiquitin C-terminal hydrolase L1 (UCHL1) — UCHL1 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 4-chlorophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8EDE · 1.799 Å · ligand 2-[(4-chlorophenyl)-methyl-amino]-~{N}'-ethanoyl-ethanehydrazide (WEU). Experimental structure, not a prediction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2004 · 12 citations
A founder effect in three large Newfoundland families with a novel clinically variable spastic ataxia and supranuclear gaze palsy
AbstractA distinctive slowly progressive neurodegenerative disorder, which falls under a new category of neurological diseases, the hereditary spastic ataxias (HSA), is described in three independently ascertained Newfoundland kindreds. HSA is a heterogeneous group of disorders in which pyramidal tract features overlap cerebellar characteristics. The families are assumed to have the same condition as, although apparently unrelated, all originate in a historically isolated cluster of rural communities and link to the same locus at 12p13, SAX1. Clinically the phenotype is very variable but lower limb hypertonicity and hyperreflexia are early and prominent generally preceded by eye movement abnormality, an impaired vertical downward saccade and a typical involuntary head jerk. These are followed by variable levels of ataxia, dysarthria, and dysphagia. Onset occurs in the first two decades and can be detected in most by early adulthood. Significant mobility problems are present by the fourth decade with a broad based ataxic and spastic gait. MRI scans of brain and spinal cord were normal. Neuropathology showed degeneration of corticospinal tracts and posterior columns and midbrain neuronal loss. The phenotype is striking in its diversity among and within families and the variability of expression can be observed within the same sibship. Pedigree analysis shows no evidence of anticipation or any sex differences in severity. The condition is unusually prevalent in the province of Newfoundland, which is characteristic of a founder effect followed by isolation and large family size. Fine mapping efforts have reduced the critical interval of the SAX1 locus to 1.9Mb. Identification of the SAX1 gene will help to clarify the pathogenesis of this type of HSA.
Neurology Genetics · 2025 · 0 citations · open access
Deciphering Spastic Ataxia
AbstractBackground and Objectives: Hereditary cerebellar ataxia (HCA) and hereditary spastic paraplegia (HSP) are rare neurologic disorders that often represent opposite ends of a shared clinical spectrum. Spastic ataxia, defined by the co-occurrence of cerebellar syndrome and overt spasticity, remains comparatively underexplored and is associated with relatively few genetic causes. The aim of this study was to characterize the clinical and genetic features of spastic ataxia in a large HCA cohort and compare them with those of nonspastic HCA. Methods: A prospective HCA cohort was initiated in 2017, incorporating annual assessments following a structured and standardized protocol. Spastic ataxia was defined as ataxia occurring in conjunction with spasticity grade ≥2 on the Modified Ashworth Scale. Patients meeting this criterion were identified; their clinical and genetic data were analyzed and compared with those of patients with nonspastic forms of HCA. The Movement Disorder Society's nomenclature for genetic disorders was adopted, using dual-prefix notation for combined phenotypes (e.g., HSP/ATX for spastic ataxia), except for entities such as MJD/SCA3 or ARSACS, which are more readily recognized by their original designations. Results: (4.3% each). A noncerebellar presentation was observed in 30 patients with spastic ataxia (53.6%) while 26 (46.6%) had cerebellar onset. After adjustment for disease duration, patients with spastic ataxia had significantly higher baseline scores on the Scale for the Assessment and Rating of Ataxia, reflecting a greater disease burden. In addition, falls were more frequent in this group. Discussion: Spastic ataxia represented a clinically and genetically distinct subgroup within HCA, marked by recessive inheritance, large genetic heterogeneity, and more severe motor impairment. Greater awareness of its heterogeneous presentations and progressive disability over time is crucial for timely diagnosis, genetic counseling, and development of tailored management strategies for these 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.
