DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for extrapyramidal and movement disease — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleExtrapyramidal and movement disease maps to a 14-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 extrapyramidal and movement 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
malate dehydrogenase 1 (MDH1) — MDH1 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 mlidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7RM9 · 1.65 Å · ligand MALONATE ION (MLI). Experimental structure, not a prediction.
What the evidence adds up to
A 1967 review of drug-induced extrapyramidal symptoms found that the literature was fraught with confusion and equivocal results, with contradictory conclusions drawn from similar observations. The authors urged future studies to be designed with adequate controls and methodological sophistication. A 2024 article on extrapyramidal examinations in psychiatry described the two categories of extrapyramidal symptoms: hyperkinetic (like Parkinson's disease) and hypokinetic (like Huntington's disease), and discussed how to elicit these signs in major mental illnesses.
A 1984 review noted that most extrapyramidal motor disorders, including those associated with Parkinson's disease and choreiform and athetoid involuntary movements, have been reproduced exclusively in primates, likely due to the complex organisation of the primate brain. Other motor disturbances, such as cervical and trunkal dystonias, ataxia, and spasticity, have been successfully induced in various mammalian species. The review stated that while numerous morphological, physiological and neurochemical data concerning the extrapyramidal system are now available, a better knowledge of their precise interrelationship is greatly needed to develop more efficient therapeutic procedures.
A 2017 study in rats used a rotenone model of Parkinson's disease to evaluate the combined use of citicoline and levodopa/carbidopa. Rotenone was administered for 14 days at 2 mg/kg/day subcutaneously, followed by 7 days of treatment. The combined therapy led to a decrease in muscle rigidity, as measured by resistance to passive flexion in the ankle joint, and a decrease in oligokinesia, shown by higher vertical and horizontal locomotor activity and reduced time for head turning and total time climbing down a pole. The combination had a more pronounced therapeutic effect on extrapyramidal disorders compared to monotherapy. A 2024 article on the appropriate use of anticholinergics noted that drug-induced movement disorders, including parkinsonism, dystonia, akathisia, and tardive dyskinesia, are common adverse effects of dopamine receptor blockers such as antipsychotics. It warned that despite similar presenting symptoms, different drug-induced movement disorders should not be treated with the same medication.
What is still missing is adequate methodological control in clinical studies, a precise understanding of the interrelationship between morphological, physiological and neurochemical data in the extrapyramidal system, and patient stratification to distinguish between the multiple etiologies of drug-induced movement disorders before applying treatments.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Psychiatry · 1967 · 45 citations
Drug-Induced Extrapyramidal Symptoms and Their Relations to Clinical Efficacy
AbstractVarious theories have been proposed relating classes of drug-induced extrapyramidal symptoms to the therapeutic actions of these drugs. But contradictory conclusions have been drawn from basically similar sets of observations; the literature on the topic is fraught with confusion and equivocal results. The authors suggest reasons for the past confusion and urge that future studies be designed with adequate controls and methodological sophistication.
International Journal of Advanced Psychiatric Nursing · 2024 · 16 citations · open access
Extrapyramidal examinations in psychiatry
AbstractIncreased motor tone, variations in movement quantity and speed, and involuntary motor activity are examples of extrapyramidal symptoms. They consist of two categories of symptoms and associated conditions: hyperkinetic (like Parkinson's disease) and hypokinetic (like Huntington's disease). This article discusses the main extrapyramidal movement disorders, the neurology behind extrapyramidal disorders, the importance of extrapyramidal signals in the major mental illnesses, and how to elicit extrapyramidal signs.
AbstractIn psychiatric literature, the term extrapyramidal syndrome has traditionally encompassed a wide variety of drug-induced movement disorders. Recently, it has become increasingly clear that the natural history, pathophysiology, and pharmacology of individual movement disorders are distinct, making this unifying term obsolete and, in fact, a source of confusion. The topic of drug-induced movement disorders is reviewed, and a classification system based on anatomy, pharmacology, and therapeutic considerations is discussed.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · 1984 · 10 citations · open access
Behaviour Correlates of Neurotransmitter Activity
AbstractMost disorders of motor activity including disturbances of muscle tone and of locomotor activity observed in patients with neurological disorders have been reproduced experimentally in animals. Most motor disorders of the extrapyramidal type including those associated with Parkinson's disease and choreiform and athetoid involuntary movements, have been reproduced exclusively in primates. This is most likely related to the highly complex organization of the extrapyramidal and related nervous mechanisms subserving the corresponding peculiar type of motor control in the primate brain. Other types of motor disturbances including cervical and trunkal dystonias, ataxia, hypotonicity, spasticity and intention tremor, however, have been successfully induced in various mammalian species. The latter types of motor disorders are related to disturbances of central nervous mechanisms which show similar patterns in the brains of different animal species. Histopathological and neurochemical changes associated with extrapyramidal disorders have been discovered and more precisely determined as a consequence of the development of new technical approaches. Therefore numerous morphological, physiological and neurochemical data concerning the extrapyramidal system are now available but a better knowledge of their precise and subtle interrelationship is greatly needed in order to develop more efficient therapeutic procedures.
S S Korsakov Journal of Neurology and Psychiatry · 2017 · 2 citations
A study of combination treatment with nacom (levodopa + carbodope) and citicoline in the model of Parkinson disease in rats
AbstractAIM: To evaluate the efficacy of the combined use of citicoline (neipilept) and levodopa/carbidopa (nakom) in the rotenone model of Parkinson's disease in rats. MATERIAL AND METHODS: Rotenone was administrated during 14 days in dose 2 mg/kg/day subcutaneously. The duration of treatment was 7 days, intragastrically. Alteration of locomotor behavior components, muscular rigidity in resistance to passive flexion in the ankle joint and signs of extrapyramidal disorders were assessed. RESULTS AND CONCLUSION: Combined therapy led to the decrease in muscle rigidity (the decrease of gibbosity in resistance to passive flexion in the ankle joint). There was a decrease in oligokinesia that emerged in higher vertical and horizontal locomotor activity of experimental animals, decrease in the time of head turning during climbing down the pole and total time of climbing down the pole. The combination of drugs had a more pronounced therapeutic effect on extrapyramidal disorders compared to monotherapy.
The Brown University Psychopharmacology Update · 2024 · 0 citations
Appropriate use of anticholinergics
AbstractDrug‐induced movement disorders, including drug‐induced parkinsonism, dystonia, akathisia, and tardive dyskinesia, are common adverse effects of dopamine receptor blockers, such as antipsychotics (especially first‐generation agents). Anticholinergic medications are commonly used to treat extrapyramidal symptoms and drug‐induced movement disorders. However, the multiple etiologies of the various types of abnormal movement disorders suggest that even though their presenting symptoms might be similar, different drug‐induced movement disorders should not be treated with the same medication.
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.
