DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for episodic kinesigenic dyskinesia 1 — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEpisodic kinesigenic dyskinesia 1 maps to a 3-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 episodic kinesigenic dyskinesia 1 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
sodium voltage-gated channel alpha subunit 8 (SCN8A) — SCN8A 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 3beta,14beta,17beta,25rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 25II · 2.5 Å · ligand (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en (9Z9). Experimental structure, not a prediction.
What the evidence adds up to
ADCY5-related dyskinesia is a childhood-onset hyperkinetic disorder that includes dystonia, chorea, and myoclonus, often with facial involvement. In a 2015 study of 50 new and previously reported cases, mutations in ADCY5 caused a mixed movement disorder with episodic worsening on a fluctuating background, sometimes painful, and many patients had axial hypotonia. Recurrent mutations at residues 418 and 726 were identified; p.R418W or p.R418Q mutations, de novo in 13 individuals and inherited in 1, produced moderate to severe disorder with axial hypotonia, limb hypertonia, paroxysmal nocturnal or diurnal dyskinesia, chorea, myoclonus, and intermittent facial dyskinesia. Somatic mosaicism was usually associated with a less severe phenotype. In one family, a p.M1029K mutation in the C2 domain caused severe dystonia, hypotonia, and chorea, and the progenitor, whose childhood-onset episodic movement disorder almost disappeared in adulthood, was mosaic for the mutation.
A 2016 case report described a patient with infantile-onset paroxysmal nonkinesigenic dyskinesia (PNKD) who failed multiple pharmaceutical agents used alone or in combination. Treatment with oxcarbazepine resulted in a substantial reduction in the frequency and severity of episodes, and the outcome was consistently favourable over four years of follow-up. The authors noted that oxcarbazepine had been effective in managing the kinesigenic form of this disorder but its use had never been reported in PNKD. They stated that blinded clinical trials are needed to verify its efficacy.
A 2023 review noted that gene discovery in paediatric movement disorders has accelerated in the next-generation sequencing era, and that investigations linking molecular and clinical aspects have often followed, exemplified by the developing stories of paroxysmal kinesigenic dyskinesia and myoclonus-dystonia syndrome. No new drug data or clinical trial results were presented in that review.
What is still missing for episodic kinesigenic dyskinesia 1 are blinded clinical trials for any drug, including oxcarbazepine, and systematic genotype-stratified studies that could clarify whether specific ADCY5 mutations predict treatment response. Funding for such trials and for larger patient cohorts to account for mosaicism and phenotypic variability remains 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.
Neurology · 2015 · 120 citations · open access
<i>ADCY5</i> -related dyskinesia
AbstractOBJECTIVE: To investigate the clinical spectrum and distinguishing features of adenylate cyclase 5 (ADCY5)-related dyskinesia and genotype-phenotype relationship. METHODS: We analyzed ADCY5 in patients with choreiform or dystonic movements by exome or targeted sequencing. Suspected mosaicism was confirmed by allele-specific amplification. We evaluated clinical features in our 50 new and previously reported cases. RESULTS: We identified 3 new families and 12 new sporadic cases with ADCY5 mutations. These mutations cause a mixed hyperkinetic disorder that includes dystonia, chorea, and myoclonus, often with facial involvement. The movements are sometimes painful and show episodic worsening on a fluctuating background. Many patients have axial hypotonia. In 2 unrelated families, a p.A726T mutation in the first cytoplasmic domain (C1) causes a relatively mild disorder of prominent facial and hand dystonia and chorea. Mutations p.R418W or p.R418Q in C1, de novo in 13 individuals and inherited in 1, produce a moderate to severe disorder with axial hypotonia, limb hypertonia, paroxysmal nocturnal or diurnal dyskinesia, chorea, myoclonus, and intermittent facial dyskinesia. Somatic mosaicism is usually associated with a less severe phenotype. In one family, a p.M1029K mutation in the C2 domain causes severe dystonia, hypotonia, and chorea. The progenitor, whose childhood-onset episodic movement disorder almost disappeared in adulthood, was mosaic for the mutation. CONCLUSIONS: ADCY5-related dyskinesia is a childhood-onset disorder with a wide range of hyperkinetic abnormal movements. Genotype-specific correlations and mosaicism play important roles in the phenotypic variability. Recurrent mutations suggest particular functional importance of residues 418 and 726 in disease pathogenesis.
Effective Treatment of Paroxysmal Nonkinesigenic Dyskinesia With Oxcarbazepine
AbstractParoxysmal nonkinesigenic dyskinesia (PNKD) is a rare chronic disorder characterized by intermittent, non-movement-related involuntary movements. The response to currently available therapies is inconsistent and temporary. We describe here a patient with infantile-onset PNKD who failed a number of pharmaceutical agents used alone or in combination. Treatment with oxcarbazepine resulted in a substantial reduction in the frequency and severity of episodes. The patient has been followed for 4 years now, and the outcome of treatment is consistently favorable. Oxcarbazepine has been effective in managing the kinesigenic form of this disorder; however, its use has never been reported in PNKD to our knowledge. Oxcarbazepine is safer and better tolerated than most of the drugs currently used for treating PNKD, but blinded clinical trials are needed to verify its efficacy in the management of this debilitating, often difficult-to-treat disease.
Somatosensory & Motor Research · 2017 · 2 citations
Transcallosal conduction in paroxysmal kinesigenic dyskinesia
AbstractOBJECTIVES: Detecting whether a possible disequilibrium between the excitatory and inhibitory interhemispheric interactions in paroxysmal kinesigenic dyskinesia (PKD) exists. METHODS: This study assessed measures of motor threshold, motor evoked potential latency, the cortical silent period, the ipsilateral silent period and the transcallosal conduction time (TCT) in PKD patients. Data were compared between the clinically affected hemisphere (aH) and the fellow hemisphere (fH). RESULTS: The transcallosal conduction time from the aH to the fH was 11.8 ms (range = 2.3-20.7) and 13.6 ms (range = 2.8-67.7) from the fH to the aH. The difference in TCT in the affected side was significant (p = .019). CONCLUSION: The findings demonstrated that, although inhibitory interneurons act normally and symmetrically between the motor cortices and transcallosal inhibition was normal and symmetrical between both sides, the onset of transcallosal inhibition was asymmetrical. The affected hemisphere's inhibition toward the unaffected hemisphere is faster compared to the inhibition provided by the fellow hemisphere. These results are consistent with an inhibitory deficit in the level of interhemispheric interactions. SIGNIFICANCE: This study revealed a defect in inhibition of the motor axis could be responsible in the pathological mechanisms of kinesigenic dyskinesia.
Advanced Genetics · 2023 · 0 citations · open access
AbstractThe pace of gene discovery in the field of pediatric movement disorders has skyrocketed in the next-generation sequencing era. With the identification of novel disease-causing genes, a flurry of investigations aiming to link the molecular and clinical aspects has often followed. Here, this process is exemplified by the developing stories of paroxysmal kinesigenic dyskinesia and myoclonus-dystonia syndrome.
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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