DeCure for Neurodevelopmental disorder with involuntary movements
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for neurodevelopmental disorder with involuntary movements — 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 moduleNeurodevelopmental disorder with involuntary movements 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 neurodevelopmental disorder with involuntary movements 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
G protein subunit alpha o1 (GNAO1) — GNAO1 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 8alphadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9BSB · 2.32 Å · ligand (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide (7LD). Experimental structure, not a prediction.
What the evidence adds up to
In a 2016 study of 28 patients with FOXG1 mutations, 93% had a mixed movement disorder phenotype, with dystonia, choreoathetosis, and orolingual/facial dyskinesias most common. Four patients with missense mutations had a milder phenotype including independent ambulation and spoken language, but hyperkinetic involuntary movements remained a major feature. Of the symptomatic treatments tried for abnormal movements, most did not emerge as clearly beneficial; four patients had a caregiver-reported response to levodopa. The authors concluded that further research on treatment strategies is necessary.
A 2002 textbook on movement disorders in children notes that these conditions are involuntary, conscious, and usually secondary to abnormalities of central nervous system neurotransmitter function, often in the basal ganglia. The book is clinically oriented and organised by signs and symptoms, covering hypotonic-rigid syndromes, dyskinesias (dystonia, athetosis, chorea, tics, myoclonus, tremor), and ataxia. It excludes disorders of pyramidal tract lesions, peripheral nervous system lesions, and cerebellar dysfunction.
A 2021 case series described four adults with rare neurodevelopmental disorders (SON, ZMYND11, DNMT1, YY1) who received a genetic diagnosis only in adulthood. All had early developmental delay and a movement disorder (dystonia, ataxia, tremor) that first appeared or worsened in adulthood, prompting neurological referral. The report expands knowledge of these four disorders beyond paediatric cases and emphasises the need for neurological surveillance extending beyond childhood.
What is still missing: larger prospective cohorts to establish prevalence of movement disorder subtypes in FOXG1 and other rare neurodevelopmental syndromes; controlled trials of symptomatic treatments such as levodopa, which currently rely on caregiver report in small numbers; and systematic adult follow-up protocols to capture late-emerging or worsening movement disorders in patients diagnosed as children.
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 · 2016 · 75 citations · open access
Delineation of the movement disorders associated with <i>FOXG1</i> mutations
AbstractOBJECTIVE: The primary objective of this research was to characterize the movement disorders associated with FOXG1 mutations. METHODS: We identified patients with FOXG1 mutations who were referred to either a tertiary movement disorder clinic or tertiary epilepsy service and retrospectively reviewed medical records, clinical investigations, neuroimaging, and available video footage. We administered a telephone-based questionnaire regarding the functional impact of the movement disorders and perceived efficacy of treatment to the caregivers of one cohort of participants. RESULTS: We identified 28 patients with FOXG1 mutations, of whom 6 had previously unreported mutations. A wide variety of movement disorders were identified, with dystonia, choreoathetosis, and orolingual/facial dyskinesias most commonly present. Ninety-three percent of patients had a mixed movement disorder phenotype. In contrast to the phenotype classically described with FOXG1 mutations, 4 patients with missense mutations had a milder phenotype, with independent ambulation, spoken language, and normocephaly. Hyperkinetic involuntary movements were a major clinical feature in these patients. Of the symptomatic treatments targeted to control abnormal involuntary movements, most did not emerge as clearly beneficial, although 4 patients had a caregiver-reported response to levodopa. CONCLUSIONS: Abnormal involuntary movements are a major feature of FOXG1 mutations. Our study delineates the spectrum of movement disorders and confirms an expanding clinical phenotype. Symptomatic treatment may be considered for severe or disabling cases, although further research regarding potential treatment strategies is necessary.
AbstractMovement Disorders in Children by Emilio Fernandez-Alvarez and Jean Aicardi London, England, MacKeith Press, 2001, 263 pp, $74.95. Movement disorders in childhood constitute a complex group of problems that are difficult to characterize and clarify. The variability of presentation of movement disorders in children, depending on age and developmental stage, adds to this difficulty. The authors of this volume, which is part of the International Review of Child Neurology series, attempt to sort through information on movement disorders and present it in a cohesive, organized manner. They succeed in providing a no-nonsense approach to a complicated topic that has not previously been well addressed. The book is clinically oriented and is organized in a signs-and-symptoms approach that is practical to the clinician. Its focus is on children and adolescents under 18 years of age. This approach is especially valuable because movement disorders of childhood vary significantly from those of adulthood, but they have not previously been brought together in one review source. The term “disorders of movement,” as used in the book, includes those conditions expressed clinically by abnormalities of movement and posture, often in association with alterations of muscular tone. These conditions are involuntary but conscious and are usually secondary to abnormalities of central nervous system neurotransmitter function, often in the basal ganglia. Disorders of pyramidal tract lesions (e.g., spastic cerebral palsy), lesions of the peripheral nervous system, and those secondary to cerebellar dysfunction are excluded. The chapters are organized according to the predominant clinical feature(s), which allows the clinician to easily find the information relevant to a particular clinical presentation. The first chapter is a clear, concise review of general concepts involved in the study of movement disorders, specifically the pathophysiology of the basal ganglia and its typical clinical manifestations. This includes normal functional organization, pathophysiology of movement disorders, main types of movement abnormalities, and the clinical context of abnormal movements (history and clinical examination). The authors divide movement disorders into three major categories that have in common a defect in the speed and accuracy of voluntary actions in the absence of muscular weakness or unwanted muscle activity. These categories include the following: (1) hypotonic-rigid syndromes (parkinsonism), (2) dyskinesias (dystonia/athetosis, chorea-ballism, tics, myoclonus, and tremor), and (3) ataxia. Eight chapters are devoted to the evaluation and management of these topics, including one chapter reviewing diseases with several types of movement disorders. Additional chapters review drug-induced movement disorders, dyskinetic movement disorders in cerebral palsy, and miscellaneous movement disorders in childhood. A final chapter examines ancillary investigations, including the recording of abnormal movements and the application of positron emission tomography (PET) technology in the study of movement disorders. The authors are two very knowledgeable and veteran child neurologists who have interwoven a review of the literature with their lifetime experience with movement disorders in an exhaustive and systematic approach. Although all movement disorders of childhood and adolescence are covered, the authors devote more space to the more commonly occurring movement disorders. Some chapter sections dealing with the less commonly occurring disorders are more esoteric in nature. However, the authors generally offer a sensible and pragmatic approach to the diagnosis and management of these problems. This volume will be extremely helpful for developmental-behavioral and neurodevelopmental pediatricians, who commonly encounter the spectrum of abnormalities of movement, from lower severity to higher severity problems.
Research Square · 2021 · 0 citations · open access
Untangling Neurodevelopmental Disorders in the Adulthood: A Movement Disorder is the Clue.
AbstractAbstract Background The genetic landscape of neurodevelopmental disorders is constantly expanding and children with early-onset neurological phenotypes increasingly receive a genetic diagnosis. Nonetheless, the awareness of the chronic course of these conditions, and consequently their recognition and management in the adult population, is still limited. Results Herein, we describe four patients with rare neurodevelopmental disorders ( SON , ZMYND11, DNMT1 and YY1- related diseases), who received a genetic allocation only in the adulthood. All these patients had an early developmental delay and displayed a movement disorder (dystonia/ataxia/tremor) which manifested for the first time, or worsened, in the adulthood, prompting the referral to a neurologist. The syndromic nature of the phenotype led eventually to the genetic testing. We report previously unrecognized features and highlight the peculiarities of the adult presentation of four neurodevelopmental disorders. Conclusions This report expands the current knowledge on four rare neurodevelopmental disorders ( SON , ZMYND11, DNMT1 and YY1 ), which was mainly based on reports from paediatric cases. This case series emphasize the importance of a tight neurological surveillance extending beyond the childhood.
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.
