DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for familial congenital mirror movements — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial congenital mirror movements maps to a 4-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 familial congenital mirror 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
RAD51 recombinase (RAD51) — RAD51 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 9TRM · 2.4 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
Seven patients with congenital mirror movements and RAD51 haploinsufficiency (mean age 33.3 years) were compared with 14 healthy volunteers. They showed abnormal decussation of the corticospinal tract, abnormal interhemispheric inhibition, and bilateral cortical activation of primary motor areas during intended unimanual movements, plus abnormal involvement of the supplementary motor area during both unimanual and bimanual movements. A Norwegian pedigree carrying a heterozygous nonsense mutation c.760C>T (p.Arg254*) in RAD51 included eight subjects: four with obvious and disabling mirror movements, four with a mild phenotype. Across six families, 32 patients with congenital mirror movements linked to RAD51 variants have been reported.
A separate family with a nonsense mutation in the DCC gene included four affected individuals across three generations. The index case, a three-year-old child, had more significant symptoms than his grandmother, who showed the mildest manifestations. Another report described a family with a novel DCC mutation and autosomal dominant inheritance. No drug treatment is described in any of these genetic studies.
An eight-year-old boy with severe mirror movements of both hands received a two-week regimen of repetitive transcranial magnetic stimulation. Mirror movement grades improved from grade 4 to grade 1 in both hands on the Woods and Teuber scale. Purdue Pegboard Test scores improved from 12 to 14 for the right hand and from 12 to 13 for the left hand. These improvements were maintained for one month after the regimen ended. At 18 months, the mirror movement grade was maintained; the right hand Pegboard score had improved to 15, and the left hand score remained at 13, without any additional stimulation or other treatment.
In 39 children aged 4–11 years and 11 normal adults, mirrored electromyographic activity during unilateral finger movements decreased with age. In younger children, involuntary mirrored activity occurred during a single finger movement; by age 11 and in adults, mirrored activity was only detected in the average of 25 sequential movements or during forceful, unfamiliar movements. Transcranial magnetic stimulation in adults showed a significant decrease in motor evoked potential from one motor cortex when the other motor cortex was conditioned, consistent with a transcallosal inhibitory effect. Slower callosal fibre conduction in children, due to late myelination, was proposed as the mechanism for mirror movements in healthy children. What remains missing is a controlled trial of repetitive transcranial magnetic stimulation in a larger, genetically characterised cohort, and any pharmacological intervention tested in patients with confirmed RAD51 or DCC mutations.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 2013 · 66 citations · open access
RAD51 deficiency disrupts the corticospinal lateralization of motor control
AbstractMirror movements are involuntary symmetrical movements of one side of the body that mirror voluntary movements of the other side. Congenital mirror movement disorder is a rare condition characterized by mirror movements that persist throughout adulthood in subjects with no other clinical abnormalities. The affected individuals have mirror movements predominating in the muscles that control the fingers and are unable to perform purely unimanual movements. Congenital mirror movement disorder thus provides a unique paradigm for studying the lateralization of motor control. We conducted a multimodal, controlled study of patients with congenital mirror movements associated with RAD51 haploinsufficiency (n = 7, mean age 33.3 ± 16.8 years) by comparison with age- and gender-matched healthy volunteers (n = 14, mean age 33.9 ± 16.1 years). We showed that patients with congenital mirror movements induced by RAD51 deficiency had: (i) an abnormal decussation of the corticospinal tract; (ii) abnormal interhemispheric inhibition and bilateral cortical activation of primary motor areas during intended unimanual movements; and (iii) an abnormal involvement of the supplementary motor area during both unimanual and bimanual movements. The lateralization of motor control thus requires a fine interplay between interhemispheric communication and corticospinal wiring. This fine interplay determines: (i) the delivery of appropriate motor plans from the supplementary motor area to the primary motor cortex; (ii) the lateralized activation of the primary motor cortex; and (iii) the unilateral transmission of the motor command to the limb involved in the intended movement. Our results also unveil an unexpected function of RAD51 in corticospinal development of the motor system.
Journal of Neurology Neurosurgery & Psychiatry · 1991 · 55 citations · open access
Central motor pathways in patients with mirror movements.
AbstractCentral motor pathways were investigated in three patients with congenital mirror movements using magnetic motor cortex stimulation. Response thresholds, amplitudes and latencies were normal. The projection of the corticomotoneuronal pathways was assessed by placing the coil over the vertex and comparing the size of responses in the first dorsal interosseous (FDI) muscles evoked by anticlockwise and clockwise [corrected] coil currents. In normal subjects, right FDI responses are larger with anticlockwise currents than with clockwise [corrected] currents at the same stimulation strength and vice versa. In two out of three patients with congenital mirror movements, this sensitivity of response amplitude to coil current direction was reversed. The third patient with congenital mirror movements and a fourth patient with acquired mirror movements had responses which were normally sensitive to current direction. These findings support the hypothesis that some cases of congenital mirror movements may be due to abnormal projection of corticomotoneuronal pathways.
Tremor and Other Hyperkinetic Movements · 2016 · 6 citations · open access
Congenital Mirror Movements Due to RAD51: Cosegregation with a Nonsense Mutation in a Norwegian Pedigree and Review of the Literature
Abstract<strong>Background:</strong> Autosomal dominant congenital mirror movements (CMM) is a neurodevelopmental disorder characterized by early onset involuntary movements of one side of the body that mirror intentional movements on the contralateral side; these persist throughout life in the absence of other neurological symptoms. The main culprit genes responsible for this condition are <em>RAD51</em> and <em>DCC</em>. This condition has only been reported in a few families, and the molecular mechanisms linking <em>RAD51</em> mutations and mirror movements (MM) are poorly understood. <strong>Methods:</strong> We collected demographic, clinical, and genetic data of a new family with CMM due to a truncating mutation of <em>RAD51</em>. We reviewed the literature to identify all reported patients with CMM due to <em>RAD51</em> mutations. <strong>Results:</strong> We identified a heterozygous nonsense mutation c.760C>T (p.Arg254*) in eight subjects: four with obvious and disabling MM, and four with a mild phenotype. Including our new family, we identified 32 patients from 6 families with CMM linked to <em>RAD51</em> variants. <strong>Discussion:</strong> Our findings further support the involvement of <em>RAD51</em> in CMM pathogenesis. Possible molecular mechanisms involved in CMM pathogenesis are discussed.
Therapeutic benefit of repetitive transcranial magnetic stimulation for severe mirror movements: A case report.
AbstractCongenital mirror movements retard typical hand functions, but no definite therapeutic modality is available to treat such movements. We report an 8-year-old boy with severe mirror movements of both hands. His mirror movements were assessed using the Woods and Teuber grading scale and his fine motor skills were also evaluated by the Purdue Pegboard Test. A 2-week regimen of repetitive transcranial magnetic stimulation produced markedly diminished mirror movement symptoms and increased the fine motor skills of both hands. Two weeks after the completion of the regimen, mirror movement grades had improved from grade 4 to 1 in both hands and the Purdue Pegboard Test results of the right and left hands also improved from 12 to 14 or 13. These improvements were maintained for 1 month after the 2-week repetitive transcranial magnetic stimulation regimen. After 18 months, the mirror movement grade was maintained and the Purdue Pegboard test score had improved to 15 for the right hand while the left hand score was maintained at 13. This occurred without any additional repetitive transcranial magnetic stimulation or other treatment. These findings suggest that repetitive transcranial magnetic stimulation for this patient had a therapeutic and long-term effect on mirror movements.
Congenital mirror movements in a family: Outcomes associated with DCC mutations
AbstractINTRODUCTION: Congenital mirror movement disorder refers to involuntary movements on one side of the body that mimic the deliberate movements on the opposite side. Congenital mirror movement is primarily associated with mutations in the DCC netrin-1 receptor (DCC) gene. CASE PRESENTATION: A 3-year-old child had been involuntarily grasping with one hand and then the other from infancy. His neuromotor development corresponded with that of his contemporaries. Identical unusual movements were also observed in his father, uncle, and grandmother within his family heritage. In the family where identical observations were noted throughout three generations, the mildest manifestations were reported in the grandmother, but our patient, the index case, had more significant symptoms. The quadruple WES study of the family indicated that all clinically symptomatic individuals harbored a nonsense mutation in the DCC gene. CONCLUSIONS: Mirror movements, typically identified in childhood, may result from genetic or neurological disorders. This study presents four individuals from the same family diagnosed with congenital mirror movement disorder.
AbstractThe mechanism of mirror movements in 11 normal adults and 39 children (aged 4-11 years) was studied in the Department of Physiology, University College London, UK. Surface electromyographic (EMG) activity was recorded from the left and right first dorsal interosseous muscles (IDI) during voluntarily activated sequential finger-thumb opposition or repetitive index finger abduction. During unilateral opposition movements (IDIvol), mirrored EMG activity (IDImm) in the homologous muscle of the opposite hand was decreased with increasing age. In the younger children, involuntary EMG activity in the IDImm was associated with activity recorded from the IDIvol during a single finger-thumb opposition. In older children, age 11 years, and adults, mirrored activity was not always present and was only detected in the average of 25 sequential finger-thumb oppositions or during performance of forceful and the less familiar index finger abduction. Mirrored activity was variable in time of onset but could occur at the same time as the voluntary burst. The slowly conducting ipsilateral corticospinal projection was not responsible for the mirrored activity recorded. In adults but not in children, transcranial magnetic stimulation showed a significant decrease in the motor evoked potential (MEP) from one motor cortex, in response to the conditioning stimulus of the other motor cortex, consistent with a transcallosal effect. Slower conducting callosal fibers in children because of late myelination would prevent the transcallosal inhibitory mechanism. The bilateral activation of both motor cortices during unilateral voluntary tasks is suggested as the likely mechanism for mirror movements in healthy children. (
Congenital mirror movements in a family with a novel mutation in the DCC gene
AbstractMirror movements are contralateral involuntary movements which mirror voluntary ones. Mirror movements are also seen in congenital disorders as Klippel-Feil syndrome and Kallmann syndrome and are also found in otherwise neurological health persons. They may occur occasionally in young children, but persistence beyond age 10 is unusual. Familiar appearance of congenital mirror movements with evidence for autosomal dominant inheritance was reported.
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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