DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spinocerebellar ataxia type 28 — 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 moduleSpinocerebellar ataxia type 28 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 spinocerebellar ataxia type 28 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
AFG3 like matrix AAA peptidase subunit 2 (AFG3L2) — AFG3L2 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6NYY · 3.0 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
Spinocerebellar ataxia type 6 is caused by a polyglutamine repeat expansion within a second CACNA1A gene product, α1ACT, whose expression is controlled by an internal ribosomal entry site (IRES) within the CACNA1A coding region. In a 2016 study, mice expressing AAV9-mediated CACNA1A IRES-driven α1ACTSCA6 exhibited early-onset ataxia, motor deficits, and Purkinje cell degeneration. The microRNA miR-3191-5p was identified as targeting the CACNA1A IRES and preferentially inhibiting IRES-driven translation of α1ACT in an Argonaute 4-dependent manner, blocking the interaction of eukaryotic initiation factors eIF4AII and eIF4GII with the IRES. AAV9-mediated delivery of miR-3191-5p protected mice from the ataxia, motor deficits, and Purkinje cell degeneration caused by CACNA1A IRES-driven α1ACTSCA6. The authors described this as proof of principle that viral delivery of an miRNA can rescue a disease phenotype through modulation of cellular IRES activity in a mouse model.
A 2025 longitudinal study of 53 patients with early stage SCA1, 2, 3, and 6 (mean age 48.7 years, mean SARA score 9.3) and 24 age-matched healthy controls found that few measures showed statistically significant changes at 12 months. At 24 months, the FARS-ADL, PROM-Ataxia total, PROM-Ataxia physical, and PROM-Ataxia ADL scores showed the strongest associations of change. The authors concluded that patient-reported or derived outcome measures can capture longitudinal change over a two-year period even in early disease, but noted more work is needed to identify outcomes that reliably capture change earlier.
A 2003 review of spinocerebellar degenerations noted that the diseases are rare, slowly progressive, often inherited, of incompletely understood pathophysiology, have few animal models and no reliable biomarkers, and no universally validated rating scale for clinical trials. At that time, at most 18 controlled trials for ataxia had been conducted over 25 years, focusing on neurotransmitter mechanisms. There were no FDA-approved drugs for SCA, and current treatment practices consisted of rehabilitation interventions and off-label use of symptomatic medications.
What is still missing for spinocerebellar ataxia type 28 specifically: no abstracts addressed this subtype at all. For SCA6, the miRNA therapy has only been tested in a mouse model, with no human data. The field as a whole lacks validated biomarkers, early-stage outcome measures that change within one year, and any FDA-approved drugs. Funding for human trials of the miR-3191-5p approach, better patient stratification for early disease, and trial designs that can detect change within 12 months remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science Translational Medicine · 2016 · 74 citations · open access
An miRNA-mediated therapy for SCA6 blocks IRES-driven translation of the <i>CACNA1A</i> second cistron
AbstractSpinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by slowly progressive ataxia and Purkinje cell degeneration. SCA6 is caused by a polyglutamine repeat expansion within a second CACNA1A gene product, α1ACT. α1ACT expression is under the control of an internal ribosomal entry site (IRES) present within the CACNA1A coding region. Whereas SCA6 allele knock-in mice show indistinguishable phenotypes from wild-type littermates, expression of SCA6-associated α1ACT (α1ACTSCA6) driven by a Purkinje cell-specific promoter in mice produces slowly progressive ataxia and cerebellar atrophy. We developed an early-onset SCA6 mouse model using an adeno-associated virus (AAV)-based gene delivery system to ectopically express CACNA1A IRES-driven α1ACTSCA6 to test the potential of CACNA1A IRES-targeting therapies. Mice expressing AAV9-mediated CACNA1A IRES-driven α1ACTSCA6 exhibited early-onset ataxia, motor deficits, and Purkinje cell degeneration. We identified miR-3191-5p as a microRNA (miRNA) that targeted CACNA1A IRES and preferentially inhibited the CACNA1A IRES-driven translation of α1ACT in an Argonaute 4 (Ago4)-dependent manner. We found that eukaryotic initiation factors (eIFs), eIF4AII and eIF4GII, interacted with the CACNA1A IRES to enhance α1ACT translation. Ago4-bound miR-3191-5p blocked the interaction of eIF4AII and eIF4GII with the CACNA1A IRES, attenuating IRES-driven α1ACT translation. Furthermore, AAV9-mediated delivery of miR-3191-5p protected mice from the ataxia, motor deficits, and Purkinje cell degeneration caused by CACNA1A IRES-driven α1ACTSCA6 We have established proof of principle that viral delivery of an miRNA can rescue a disease phenotype through modulation of cellular IRES activity in a mouse model.
Movement Disorders Clinical Practice · 2025 · 4 citations · open access
Longitudinal Changes in Patient‐ and Clinical‐Reported Outcomes in Early Spinocerebellar Ataxia Types 1, 2, 3, and 6 from the <scp>IDEA</scp> Study
AbstractBACKGROUND: Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients. OBJECTIVES: To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6. METHODS: We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls. Participants were seen every 6 months for 2 years. Mixed models were used to estimate change over 12- and 24-months of follow-up. Changes on the FARS-FS and PGI-C were used as anchors to estimate meaningful changes. RESULTS: Among persons with SCA, mean age was 48.7 years and mean SARA score was 9.3. Few measures showed statistically significant changes at 12 months. At 24-months, the FARS-ADL, PROM-Ataxia total, PROM-Ataxia physical, and PROM-Ataxia ADL scores showed the strongest associations of change. CONCLUSIONS: Patient reported or derived outcome measures, such as FARS-ADL and ADL sub domain of the PROM-Ataxia, can capture longitudinal change in patients' symptom experience over a 2-year period and its impact on daily activities, even in those with early disease. More work is needed to identify outcomes that reliably capture change earlier.
Expert Opinion on Pharmacotherapy · 2003 · 4 citations
Spinocerebellar degeneration
AbstractThe spinocerebellar degenerations/ataxias (SCAs) are a diverse group of rare, slowly progressive, neurological diseases, often inherited but of incompletely understood pathophysiology, which affect the cerebellum and its related pathways. They have few animal models and share no reliable biomarkers. They have, as yet, no universally validated rating scale for use in clinical trials. In the past 25 years, there have been, at most, 18 controlled (Class 1) trials for ataxia, which have focused on neurotransmitter mechanisms. There is currently only one National Institute of Neurological Disorders and Stroke-sponsored drug trial for ataxia (Phase I study of idebenone in Friedreich's ataxia). There are, as yet, no FDA-approved drugs for SCA. Current treatment practices encompass rehabilitation interventions and off-label use of symptomatic medications [1,2].
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.
