DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for stereotypic movement disorder — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleStereotypic movement disorder maps to a 10-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 stereotypic movement disorder 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
methyl-CpG binding protein 2 (MECP2) — MECP2 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…
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RCSB Protein Data Bank · entry 6OGK · 1.65 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
The two 2021 reviews on clinicogenetic correlations in movement disorders do not report any treatment outcomes. They describe how next-generation sequencing has revealed that mutations in a single gene can produce multiple distinct phenotypes (pleiotropy, variable expressivity, incomplete penetrance), and conversely that a single movement disorder phenotype can arise from mutations in many different genes. The authors note that there is no gold standard for diagnosis, that clinical classification systems overlap and are interpreted inconsistently, and that variant interpretation guidelines remain problematic. They call for deep phenotyping, close clinician-laboratory collaboration, and periodic reanalysis of sequencing data to improve diagnostic yield.
The 2022 German-language anthology on movement therapy for psychiatric disorders states that movement therapy is an indispensable tool in multimodal treatment and can alleviate disorder-specific symptoms across the lifespan, but it provides no quantitative data on efficacy, no sample sizes, and no specific results for stereotypic movement disorder. The 2023 DystoGen compendium paper describes a database of 28,377 genetic variants from 118 genes associated with monogenic movement disorders, of which 5,118 (18.03%) are classified as pathogenic or likely pathogenic according to ACMG/AMP guidelines. That resource does not report any therapeutic intervention or clinical trial.
No abstract in this set tests a drug for stereotypic movement disorder. There are no response rates, survival figures, or controlled trial results to report. What is missing is any clinical trial of a pharmacological intervention for this condition, any patient stratification strategy based on the genetic heterogeneity described, and the funding or study design needed to move from genetic annotation to treatment testing.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Movement Disorders Clinical Practice · 2021 · 60 citations · open access
Challenges in Clinicogenetic Correlations: One Gene – Many Phenotypes
AbstractBACKGROUND: Progress in genetics - particularly the advent of next-generation sequencing (NGS) - has enabled an unparalleled gene discovery and revealed unmatched complexity of genotype-phenotype correlations in movement disorders. Among other things, it has emerged that mutations in one and the same gene can cause multiple, often markedly different phenotypes. Consequently, movement disorder specialists have increasingly experienced challenges in clinicogenetic correlations. OBJECTIVES: To deconstruct biological phenomena and mechanistic bases of phenotypic heterogeneity in monogenic movement disorders and neurodegenerative diseases. To discuss the evolving role of movement disorder specialists in reshaping disease phenotypes in the NGS era. METHODS: This scoping review details phenomena contributing to phenotypic heterogeneity and their underlying mechanisms. RESULTS: Three phenomena contribute to phenotypic heterogeneity, namely incomplete penetrance, variable expressivity and pleiotropy. Their underlying mechanisms, which are often shared across phenomena and non-mutually exclusive, are not fully elucidated. They involve genetic factors (ie, different mutation types, dynamic mutations, somatic mosaicism, intragenic intra- and inter-allelic interactions, modifiers and epistatic genes, mitochondrial heteroplasmy), epigenetic factors (ie, genomic imprinting, X-chromosome inactivation, modulation of genetic and chromosomal defects), and environmental factors. CONCLUSION: Movement disorders is unique in its reliance on clinical judgment to accurately define disease phenotypes. This has been reaffirmed by the NGS revolution, which provides ever-growing sequencing data and fuels challenges in variant pathogenicity assertions for such clinically heterogeneous disorders. Deep phenotyping, with characterization and continual updating of "core" phenotypes, and comprehension of determinants of genotype-phenotype complex relationships are crucial for clinicogenetic correlations and have implications for the diagnosis, treatment and counseling.
Movement Disorders Clinical Practice · 2021 · 22 citations · open access
Challenges in Clinicogenetic Correlations: One Phenotype – Many Genes
AbstractBACKGROUND: In the field of movement disorders, what you see (phenotype) is seldom what you get (genotype). Whereas 1 phenotype was previously associated to 1 gene, the advent of next-generation sequencing (NGS) has facilitated an exponential increase in disease-causing genes and genotype-phenotype correlations, and the "one-phenotype-many-genes" paradigm has become prominent. OBJECTIVES: To highlight the "one-phenotype-many-genes" paradigm by discussing the main challenges, perspectives on how to address them, and future directions. METHODS: We performed a scoping review of the various aspects involved in identifying the underlying molecular cause of a movement disorder phenotype. RESULTS: The notable challenges are (1) the lack of gold standards, overlap in clinical spectrum of different movement disorders, and variability in the interpretation of classification systems; (2) selecting which patients benefit from genetic tests and the choice of genetic testing; (3) problems in the variant interpretation guidelines; (4) the filtering of variants associated with disease; and (5) the lack of standardized, complete, and up-to-date gene lists. Perspectives to address these include (1) deep phenotyping and genotype-phenotype integration, (2) adherence to phenotype-specific diagnostic algorithms, (3) implementation of current and complementary bioinformatic tools, (4) a clinical-molecular diagnosis through close collaboration between clinicians and genetic laboratories, and (5) ongoing curation of gene lists and periodic reanalysis of genetic sequencing data. CONCLUSIONS: Despite the rapidly emerging possibilities of NGS, there are still many steps to take to improve the genetic diagnostic yield. Future directions, including post-NGS phenotyping and cohort analyses enriched by genotype-phenotype integration and gene networks, ought to be pursued to accelerate identification of disease-causing genes and further improve our understanding of disease biology.
Academia – ein Verlag in der Nomos Verlagsgesellschaft eBooks · 2022 · 0 citations
Bewegungstherapie bei psychischen Erkrankungen in der Lebensspanne
AbstractMovement therapy is an indispensable tool in the multimodal treatment approach. Regardless of age, its impact on activating and strengthening physical, mental and social resources is crucial. It offers a variety of therapeutical approaches to behavioral patterns of patients and it alleviates disorder-specific symptoms. In this anthology, experts shed light on a variety of facets regarding movement therapy for children, teens, adults and seniors. The contributions combine interesting facts and new developments in practice and academia and offer valuable impulses and suggestions on applying them for different diagnosis groups and treatment settings.
bioRxiv (Cold Spring Harbor Laboratory) · 2023 · 0 citations · open access
DystoGen Compendium: A comprehensive resource of ACMG annotated movement disorder associated genetic variants
AbstractAbstract Purpose In recent years, the advent of high throughput sequencing techniques has led to the identification of a number of genetic variants across different genes that are associated with movement disorders. However, the under-appreciation of the variant spectrum in movement disorders and the lack of consolidated and systematic evidence-based annotation of these variants has long undermined the true potential of genomic approaches to expedite precision medicine. Methods We manually curated the genetic variants from a panel of 118 genes that have been associated with monogenic causes of movement disorders and systematically annotated them according to ACMG & AMP (American College of Medical Genetics and the Association of Molecular Pathologists) guidelines. Results Data integration after systematic classification of variants according to ACMG & AMP guidelines showed 5118 pathogenic/likely pathogenic variants accounting for 18.03% of the total unique variants being annotated. This data and annotations are available in a comprehensive online compendium DystoGen. Conclusion To the best of our knowledge, this is the most comprehensive compendium of genetic variants in movement disorders annotated as per the ACMG & AMP guidelines for pathogenicity. The compendium indexes 28377 variants along with a wide array of information including the geographical origin of the variant, global distribution, and population allele frequency. The resource has been made available in the URL https://clingen.igib.res.in/dystogen/ .
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.
