DeCure for Biotin-responsive basal ganglia disease
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for biotin-responsive basal ganglia disease — 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 moduleBiotin-responsive basal ganglia disease 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 biotin-responsive basal ganglia disease 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
solute carrier family 19 member 3 (SLC19A3) — SLC19A3 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-[2-(pyrrolidin-1-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8Z7Y · 3.02 Å · ligand N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzenesulfonamide (2TA). Experimental structure, not a prediction.
What the evidence adds up to
Two European adults, a 33-year-old man and his 29-year-old sister of Portuguese ancestry, presented with recurrent encephalopathy episodes, generalised dystonia, epilepsy, and bilateral hyperintensities of the caudate and putamen. High doses of biotin or a combination of biotin and thiamine produced spectacular clinical and radiologic improvement. Sequencing revealed two novel SLC19A3 mutations creating premature stop codons. The authors concluded that a therapeutic trial of high-dose biotin and thiamine is mandatory in any unexplained encephalopathy with bilateral lesions of the putamen and caudate nuclei.
A retrospective review of 15 genetically proven Middle Eastern cases examined neuroimaging before and after biotin and thiamine therapy. Brain MRI at onset showed bilateral caudate lesions with complete or partial putamen involvement and sparing of the globus pallidus in all cases. In 80% there were abnormal signals in the mesencephalon, cerebral cortical-subcortical regions, and thalami. In 53% of advanced cases patchy deep white matter affection was found; the cerebellum was involved in 13.3%. After treatment, signal abnormalities in the mesencephalon, cortex, and white matter disappeared, but caudate and putamen necrosis persisted in all patients, including those who became asymptomatic.
One case report described a patient who presented much earlier, was milder, and responded better to lower doses of biotin than the ten previously reported cases. The authors noted this might represent a new entity or a milder form of the same condition. Another case report described a childhood case with dramatic response to biotin therapy, corroborated by neuroimaging.
What remains missing is prospective trial data with standardised dosing regimens, long-term follow-up beyond two to eight weeks, and systematic investigation of whether thiamine adds benefit beyond biotin alone. The condition is underdiagnosed, and no large-scale screening or treatment protocol has been funded. Patient stratification by genotype, age at onset, and lesion pattern on MRI has not been prospectively validated.
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 · 2010 · 117 citations
Biotin-Responsive Basal Ganglia Disease in Ethnic Europeans With Novel SLC19A3 Mutations
AbstractOBJECTIVE: To report the first 2 European cases of biotin-responsive basal ganglia disease and novel SLC19A3 mutations. DESIGN: Case reports. SETTING: University hospital. Patients A 33-year-old man and his 29-year-old sister, both of Portuguese ancestry, presented with recurrent episodes of encephalopathy. Between episodes patients exhibited generalized dystonia, epilepsy, and bilateral hyperintensities of the caudate and putamen. MAIN OUTCOME MEASURES: Clinical and radiologic findings. RESULTS: Administration of high doses of biotin or of a combination of biotin and thiamine during encephalopathies resulted in spectacular clinical and radiologic improvement in both patients. Sequencing of the SLC19A3 disclosed 2 novel mutations, both of which created premature stop codons in the protein sequence of hTHTR2. CONCLUSION: This study demonstrates that biotin-responsive basal ganglia disease is a panethnic condition. A therapeutic trial with high doses of biotin and thiamine seems mandatory in every unexplained encephalopathy with bilateral lesions of putamen and caudate nuclei.
American Journal of Neuroradiology · 2014 · 42 citations · open access
Biotin-Responsive Basal Ganglia Disease: Neuroimaging Features before and after Treatment
AbstractBACKGROUND AND PURPOSE: Biotin-responsive basal ganglia disease is an autosomal recessive neurometabolic disorder presenting with subacute encephalopathy that can cause death if left untreated. The purpose of this study is to assess the neuroimaging and clinical features of the disease before and after treatment with biotin. MATERIALS AND METHODS: We retrospectively reviewed the clinical, laboratory, and neuroimaging features of 15 genetically-proved Middle Eastern cases of biotin-responsive basal ganglia disease. Brain MR imaging was done at the onset of symptoms in all cases and within 2-8 weeks after biotin and thiamine therapy in 14 patients. The MR imaging datasets were analyzed according to lesion location, extent, and distribution. RESULTS: Brain MR imaging showed bilateral lesions in the caudate nuclei with complete or partial involvement of the putamen and sparing of the globus pallidus in all cases. In 80%, discrete abnormal signals were observed in the mesencephalon, cerebral cortical-subcortical regions, and thalami. In 53%, when the disease was advanced, patchy deep white matter affection was found. The cerebellum was involved in 13.3%. The signal abnormality of the mesencephalon, cortex, and white matter disappeared after treatment whereas the caudate and putamen necrosis persisted in all patients, including those who became asymptomatic. CONCLUSIONS: Biotin-responsive basal ganglia disease is a treatable underdiagnosed disease. It should be suspected in pediatric patients with unexplained encephalopathy whose brain MR imaging shows bilateral and symmetric lesions in the caudate heads and putamen, with or without involvement of mesencephalon, thalami, and cortical-subcortical regions, as the therapeutic trial of biotin and thiamine can be lifesaving.
Biotin-Responsive Basal Ganglia Disease: Case Report and Review of the Literature
AbstractBiotin-responsive basal ganglia disease is a rare entity of which 10 cases have been reported in the literature. We report a case of biotin-responsive basal ganglia disease with similarities and differences compared to the previously reported cases by Ozand et al. Our case presented much earlier, was milder and responded better to lower doses of biotin, compared to the cases reported previously. Since our case showed differences with those in the literature, it might represent a new entity or a milder form of the same entity.
Biotin-Responsive Basal Ganglia Disease: A Treatable and Reversible Neurological Disorder of Childhood
AbstractBiotin-responsive basal ganglia disease is a rare childhood neurological disorder of uncertain etiology that is treatable if suspected and diagnosed. Only few cases have been reported earlier in literature. We report a case of biotin-responsive basal ganglia disease suspected clinically, corroborated by neuroimaging and a dramatic response to biotin therapy.
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.
