DeCure for Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset — 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 moduleNeurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset 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 neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset 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
sequestosome 1 (SQSTM1) — SQSTM1 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6TGY · 3.5 Å · ligand none (apo structure). 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.
European Journal of Neurology · 2012 · 46 citations · open access
Pontine‐to‐midbrain ratio indexes ocular‐motor function and illness stage in adult Niemann–Pick disease type C
AbstractBACKGROUND AND PURPOSE: Niemann-Pick disease type C (NPC) is a progressive neurovisceral disorder associated with dystonia, ataxia and a characteristic gaze palsy. Neuropathological studies have demonstrated brainstem atrophy associated with neuronal inclusions and loss, and neurofibrillary tangles, although it is not known whether this pathology can be detected in vivo or how these changes relate to illness variables, particularly ocular-motor changes. Our aim was to utilize a method for brainstem atrophy, validated in progressive supranuclear palsy (PSP), in a group of adult patients with NPC, and explore its relationship to illness variables and ocular-motor functioning. METHODS: We calculated the midbrain and pontine area, and pontine-to-midbrain ratio (PMR) from midsagittal images of 10 adult patients with NPC and 27 age- and gender-matched controls. Measures were correlated with illness variables, and measures of horizontal saccadic functioning. RESULTS: Pontine-to-midbrain ratio was 14% higher in the NPC group, but this difference was not significant. However, PMR showed a significant positive correlation with duration of illness and a measure of illness severity. Furthermore, PMR was significantly negatively correlated with saccadic peak velocity and gain, and self-paced saccadic performance. CONCLUSIONS: Pontine-to-midbrain ratio was increased in adult patients with NPC compared to controls, although not to the same degree as previously described in PSP, which also presents with significant gaze palsy. These changes were driven predominantly by progressive midbrain atrophy. The strong correlation with illness and ocular-motor variables suggests that it may be a useful marker for illness progression in NPC.
Movement Disorders Clinical Practice · 2020 · 8 citations · open access
Two Patients with Niemann Pick Disease Type C Diagnosed in the Seventh Decade of Life
AbstractBACKGROUND: Niemann-Pick disease type C (NPC) is a rare, autosomal recessive lysosomal lipid storage disorder. It may present with cerebellar ataxia, vertical supranuclear gaze palsy, and cognitive impairment, and the age of symptom onset in adult-onset NPC is usually earlier than the fourth decade. CASES: We present 2 patients with adult-onset NPC diagnosed in the seventh decade of life. The slow motor progression and subtle findings of supranuclear vertical gaze palsy and ataxia can lead to a delayed diagnosis and misdiagnosis with parkinsonian disorders, particularly progressive supranuclear palsy. CONCLUSION: This report highlights and differentiates key clinical characteristics between NPC and parkinsonian disorders. It is important to consider NPC in the differential diagnosis when patients present with slowed vertical saccades, vertical supranuclear gaze palsy, ataxia, and cognitive impairment present at any age. This will allow appropriate and prompt treatment with miglustat and novel experimental therapies.
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.
