DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Kufor-Rakeb syndrome — 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 moduleKufor-Rakeb syndrome 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 kufor-rakeb 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
ATPase cation transporting 13A2 (ATP13A2) — ATP13A2 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 befdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7M5X · 2.7 Å · ligand BERYLLIUM TRIFLUORIDE ION (BEF). Experimental structure, not a prediction.
What the evidence adds up to
Kufor-Rakeb syndrome is an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration that maps to a 9 cM region of chromosome 1p36, with a maximum multipoint lod score of 3.6. Onset is in the teenage years with Parkinson’s disease features plus spasticity, supranuclear upgaze paresis, and dementia. Brain scans show atrophy of the globus pallidus and pyramids, and later widespread cerebral atrophy. The syndrome is caused by loss-of-function mutations in the ATP13A2 gene at the PARK9 locus. A 2017 study of five Iranian siblings carrying a homozygous nonsense mutation c.2455C>T;p.Arg819* in ATP13A2 reported cognitive deficits, hypokinesia, rigidity, spasticity, brisk deep tendon reflexes, upward gaze palsy, tremor, and facial-faucial-finger mini-myoclonus in all affected siblings. Two had seizures, and the most severely affected sibling demonstrated severe action myoclonus, which had not been reported before.
A 2016 case report described a 24-year-old male with a one-year history of abnormal behaviour, apathy, dystonia, slowness, anarthria, tremulousness, and cognitive decline. Examination showed cognitive decline, supranuclear upgaze paresis, spasticity, hyperreflexia with extensor plantar response, tremor, and facial-faucial-finger mini myoclonus. MRI brain revealed bilateral cerebral, brainstem and cerebellar generalised atrophy, and DWI showed hypointensity in putamen and globus pallidus surrounding a hyperintense lesion described as an “eye of tiger” sign, which had not been reported earlier in the literature. The patient showed minimal improvement initially on trihexyphenidyl and levodopa plus carbidopa combination, but the response was not consistent on follow-up, and he became bed-bound within one and a half years after disease onset.
A 2019 case report described a 32-year-old male with Kufor-Rakeb syndrome who presented with daily behavioural outbursts and psychotic symptoms. At first assessment, the CGI scale was estimated at 5 (“Markedly ill”). Aripiprazole was started at 2 mg and increased to 3 mg. Two years later, psychotic symptoms were judged to be “much improved” (CGI-C = 2). The report states that this improvement occurred without drug-induced motor side effects, and suggests that low-dose aripiprazole (2–5 mg) is effective and tolerated in patients with KRS. This is a single case report, not a controlled trial.
No treatment has been shown to alter the course of the neurodegeneration itself. The response to levodopa and trihexyphenidyl was inconsistent in the one case that reported it. What is missing are any controlled trials, any therapies targeting the underlying ATP13A2 deficiency, and any systematic data on patient stratification by mutation type or disease stage. Funding for natural history studies and for preclinical work on ATP13A2 biology remains limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Medical Genetics · 2001 · 151 citations · open access
Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36
AbstractKufor-Rakeb syndrome is an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration. The onset is in the teenage years with clinical features of Parkinson's disease plus spasticity, supranuclear upgaze paresis, and dementia. Brain scans show atrophy of the globus pallidus and pyramids and, later, widespread cerebral atrophy. We report linkage in Kufor-Rakeb syndrome to a 9 cM region of chromosome 1p36 delineated by the markers D1S436 and D1S2843, with a maximum multipoint lod score of 3.6.
Movement Disorders Clinical Practice · 2017 · 18 citations · open access
Action Myoclonus and Seizure in Kufor‐Rakeb Syndrome
AbstractAbstract View Supplementary Video 1 View Supplementary Video 2 View Supplementary Video 3 View Supplementary Video 4 View Supplementary Video 5 Background Kufor‐Rakeb syndrome ( KRS ) is a rare autosomal recessive neurologic disease with diverse phenotypic features. Herein we report an Iranian KRS family with seizure and action myoclonus in addition to other typical manifestations of this syndrome. Method All family members underwent careful neurologic examination. Exome sequencing was performed and ATP 13A2 variation genotyped in all family members. Results Cognitive deficits, hypokinesia, rigidity, spasticity, brisk deep tendon reflexes, upward gaze palsy, tremor, and facial‐faucial‐finger mini‐myoclonus were the common manifestations of all affected siblings. Two cases had seizure and the most severely affected sibling demonstrated severe action myoclonus. Exome sequencing identified a homozygous nonsense mutation c.2455C>T;p.Arg819* in ATP 13A2 gene. Conclusions We reported five KRS affected siblings who manifested myoclonus and seizure. The most severely affected one demonstrated action myoclonus, which has not been reported so far.
Successful treatment of psychosis in a patient with Kufor-Rakeb syndrome with low dose aripiprazole: a case report
AbstractWe present a case of a 32-year-old male with Kufor-Rakeb syndrome (KRS), a form of juvenile parkinsonism due to mutations of the ATP13A2 gene at PARK9 locus. The patient was seen for daily behavioral outbursts and psychotic symptoms. At first assessment, CGI scale was estimated at 5; "Markedly ill". Aripiprazole was started at 2 mg and then increased to 3 mg. Two years later, psychotic symptoms were judged to be "much improved" (CGI-C = 2). This significant improvement without drug-induced motor side effects suggests that aripiprazole at low doses (2-5 mg) is effective and tolerated in patients with KRS.
Indian Journal of Medical Specialities · 2016 · 2 citations
Kufor–Rakeb syndrome (KRS): Clinico-radiological phenotype of a probable sporadic case with “eye of tiger” sign
AbstractKufor–Rakeb syndrome (KRS) is a rare autosomal recessive form of pallidopyramidal degeneration, supranuclear upgaze paresis and cognitive decline, first described in Kufor–Rakeb. Disease pathogenesis of KRS is due to loss of function of ATP13A2 (PARK9) gene which was identified by Ramirez et al. A 24 years old adolescent male presented with one-year history of abnormal behavior followed by apathy since 3 months. Subsequently, he developed one episode of abrupt abnormal twisting posture of left upper limb and lower limb lasting for an hour which preceded slowness in his daily activities and anarthria. He also developed tremulousness in all four extremities and cognitive decline in the form of difficulty in simple calculation and naming. On neurological examination he had cognitive decline, supranuclear upgaze paresis, pyramidal features in the form of spasticity, hyperreflexia with extensor plantar response and extrapyramidal features in the form of tremor and myoclonus suggestive of facial-faucial-finger mini myoclonus (FFF mini myoclonus) without sensory involvement. MRI brain revealed bilateral cerebral, brainstem and cerebellar generalized atrophy and DWI showed hypo intensity in putamen and globus pallidus surrounding a hyperintense lesion like “eye of tiger” sign. He showed minimal improvement initially on trihexyphenidyl and levodopa plus carbidopa combination but response was not consistent on follow up and he became bed bound within one and half years after disease onset. In our patient dystonia was an early feature and interestingly MRI brain showed “eye of tiger” sign which has not been reported earlier in the literature.
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.
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