DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spastic quadriplegic cerebral palsy — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSpastic quadriplegic cerebral palsy maps to a 5-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 spastic quadriplegic cerebral palsy 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
glutamate decarboxylase 1 (GAD1) — GAD1 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 hlddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3VP6 · 2.1 Å · ligand 4-oxo-4H-pyran-2,6-dicarboxylic acid (HLD). Experimental structure, not a prediction.
What the evidence adds up to
In 115 boys with cryptogenic infantile spasms, an expansion of the first polyalanine tract of the ARX gene from 10 to 17 GCG repeats was found in six boys (5.2%) from four families. All six had infantile spasms, severe mental retardation, and generalised dystonia that appeared around six months of age and worsened to stable severe quadriplegic dyskinesia by age two. Three children had recurrent, life-threatening status dystonicus. Brain MRI in four children showed multiple small foci of abnormal cavitation and increased T2 signal in the putamina. The authors concluded that ARX gene testing should be considered in boys with infantile spasms and dyskinetic cerebral palsy without a consistent perinatal history. Separately, three unrelated individuals with very-early-onset (before seven months) complex hereditary spastic paraplegia carried novel ATL1 pathogenic variants: a de novo missense p.(Lys406Glu), a homozygous frameshift p.(Arg403Glufs*3), and a homozygous missense p.(Tyr367His). Their phenotypes included axial hypotonia, spastic quadriplegia, dystonia, seizures, and intellectual disability, and in two of the three led to an initial diagnosis of cerebral palsy. The heterozygous parents were asymptomatic, supporting possible autosomal recessive forms of SPG3A.
A single case report described a 16-year-old girl with spastic quadriplegic cerebral palsy from premature birth and periventricular leukomalacia who had a dramatic improvement in motor function after treatment with carbidopa/levodopa. Kinematic and electromyographic analyses showed that levodopa decreased muscle co-contraction, decreased unwanted movements, and improved her ability to maintain a steady arm posture. The authors suggested levodopa be considered as adjunct therapy, but this is a single unblinded observation with no controls.
A randomised trial compared Adeli suit treatment with neurodevelopmental treatment in 24 children with cerebral palsy (GMFCS Levels II to IV). Twelve children received AST (mean age 8.3 years; five with spastic/mixed quadriplegia) and twelve received NDT (mean age 8.1 years; seven with spastic/mixed quadriplegia). Both groups were treated for four weeks (two hours daily, five days per week). Small but significant time effects for GMFM-66 and mechanical efficiency index were noted after one month in both groups, greater than expected from natural maturation. Improvements in motor skills and their retention nine months after treatment were not significantly different between the two modes. Post hoc analysis suggested a greater increase in mechanical efficiency in AST than NDT at ten months (p=0.004), predominantly in children with higher motor function (GMFCS Levels II and III), but without a corresponding gain in gross motor skills.
A narrative review on management of spastic hips in cerebral palsy described conservative and surgical procedures and noted new treatments are being explored, but gave no new trial data. What remains missing are adequately powered, blinded, controlled trials of any pharmacological intervention for spastic quadriplegic cerebral palsy, including levodopa; genetic stratification of patients to identify who might benefit from specific treatments; and funding for trials that can move beyond single case reports and small underpowered comparisons of physiotherapy modalities.
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 · 2007 · 147 citations
Expansion of the first PolyA tract of <i>ARX</i> causes infantile spasms and status dystonicus
AbstractBACKGROUND: ARX is a paired-type homeobox gene located on the X chromosome that contains five exons with four polyalanine (PolyA) tracts, a homeodomain, and a conserved C-terminal aristaless domain. Studies in humans have demonstrated remarkable pleiotropy: malformation phenotypes are associated with protein truncation mutations and missense mutations in the homeobox; nonmalformation phenotypes, including X-linked infantile spasms (ISS), are associated with missense mutations outside of the homeobox and expansion of the PolyA tracts. OBJECTIVE: To investigate the role of ARX, we performed mutation analysis in 115 boys with cryptogenic ISS. This included two pairs of brothers. RESULTS: We found an expansion of the trinucleotide repeat that codes for the first PolyA tract from 10 to 17 GCG repeats (c.333_334ins[GCG]7) in six boys (5.2%) ages 2 to 14, from four families, including the two pairs of brothers. In addition to ISS, all six boys had severe mental retardation and generalized dystonia that appeared around the age of 6 months and worsened, eventually leading to stable severe quadriplegic dyskinesia within age 2 years. Three children experienced recurrent, life-threatening status dystonicus. In four children brain MRI showed multiple small foci of abnormal cavitation on T1 and increased signal intensity on T2 in the putamina, possibly reflecting progressive multifocal loss of tissue. CONCLUSION: The phenotype of infantile spasms with severe dyskinetic quadriparesis increases the number of human disorders that result from the pathologic expansion of single alanine repeats. ARX gene testing should be considered in boys with infantile spasms and dyskinetic cerebral palsy in the absence of a consistent perinatal history.
Developmental Medicine & Child Neurology · 2006 · 86 citations · open access
Comparison of efficacy of Adeli suit and neurodevelopmental treatments in children with cerebral palsy
AbstractThis study compared the efficacy of Adeli suit treatment (AST) with neurodevelopmental treatment (NDT) in children with cerebral palsy (CP). Twenty-four children with CP, Levels II to IV according to the Gross Motor Function Classification System (GMFCS), were matched by age and functional status and randomly assigned to the AST or NDT treatment groups. In the AST group (n=12; eight males, four females; mean age 8.3 y [SD 2.0]), six children had spastic/ataxic diplegia, one triplegia and five spastic/mixed quadriplegia. In the NDT group (n=12; nine males, three females; mean age 8.1 y [SD 2.2]), five children had spastic diplegia and seven had spastic/mixed quadriplegia. Both groups were treated for 4 weeks (2 hours daily, 5 days per week, 20 sessions). To compare treatments, the Gross Motor Function Measure (GMFM-66) and the mechanical efficiency index (EIHB) during stair-climbing were measured at baseline, immediately after 1 month of treatment, and 10 months after baseline. The small but significant time effects for GMFM-66 and EIHB that were noted after 1 month of both intensive physiotherapy courses were greater than expected from natural maturation of children with CP at this age. Improvements in motor skills and their retention 9 months after treatment were not significantly different between the two treatment modes. Post hoc analysis indicated a greater increase in EIHB after 1 month (p=0.16) and 10 months (p=0.004) in AST than that in NDT, predominantly in the children with higher motor function (GMFCS Levels II and III). The results suggest that AST might improve mechanical efficiency without a corresponding gain in gross motor skills, especially in children with higher levels of motor function.
Motor benefit from levodopa in spastic quadriplegic cerebral palsy
AbstractWe report on a 16-year-old girl with spastic quadriplegic cerebral palsy associated with premature birth and typical periventricular leukomalacia, who had a dramatic improvement in motor function after treatment with carbidopa/levodopa. Kinematic and electromyographic analyses of reaching movements demonstrate that levodopa decreased muscle co-contraction, decreased unwanted movements, and improved her ability to maintain a steady arm posture. These findings suggest that levodopa be considered as an adjunct therapy for the treatment of spastic quadriplegic cerebral palsy.
Current Concept and Management of Spastic Hip in Children: A Narrative Review
AbstractCerebral palsy (CP) is a non-progressive motor condition that hinders the development of movement and posture. One of the common problems faced in CP is spastic hips, which can cause discomfort, deformity, and functional restrictions. This review article seeks to offer a thorough summary of the most recent methods for treating spastic hips in cerebral palsy patients. Additionally, it describes the success and potential risks of various conservative and surgical procedures. It also looks at new treatments and potential avenues for managing this complicated ailment.
Journal of Neurology · 2024 · 2 citations · open access
Patients with complex and very-early-onset ATL1-related spastic paraplegia offer insights on genotype/phenotype correlations and support for autosomal recessive forms of SPG3A
AbstractSpastic paraplegia type 3A (SPG3A) is the second most common form of hereditary spastic paraplegia (HSP). This autosomal-dominant-inherited motor disorder is caused by heterozygous variants in the ATL1 gene which usually presents as a pure childhood-onset spastic paraplegia. Affected individuals present muscle weakness and spasticity in the lower limbs, with symptom onset in the first decade of life. Individuals with SPG3A typically present a slow progression and remain ambulatory throughout their life. Here we report three unrelated individuals presenting with very-early-onset (before 7 months) complex, and severe HSP phenotypes (axial hypotonia, spastic quadriplegia, dystonia, seizures and intellectual disability). For 2 of the 3 patients, these phenotypes led to the initial diagnosis of cerebral palsy (CP). These individuals carried novel ATL1 pathogenic variants (a de novo ATL1 missense p.(Lys406Glu), a homozygous frameshift p.(Arg403Glufs*3) and a homozygous missense variant (p.Tyr367His)). The parents carrying the heterozygous frameshift and missense variants were asymptomatic. Through these observations, we increase the knowledge on genotype-phenotype correlations in SPG3A and offer additional proof for possible autosomal recessive forms of SPG3A, while raising awareness on these exceptional phenotypes. Their ability to mimic CP also implies that genetic testing should be considered for patients with atypical forms of CP, given the implications for genetic counseling.
Iranian Journal of Pediatrics · 2018 · 2 citations · open access
The Efficacy of Cerebrolysin in Improvement of Spasticity in Children with Cerebral Palsy: A Clinical Trial
AbstractBackground: Cerebral Palsy (CP) constitutes a heterogeneous group of developmental disorders resulting from damage to the brain which affects motor system. Cerebrolysin, as a neurotrophic peptide has been used for improving symptoms of patients suffering from neurodegenerative disorders. Objectives: Due to the presence of limited information about the usefulness of Cerebrolysin in CP, this study was performed for the evaluation of Cerebrolysin in the management of spasticity in children with CP. Methods: 26 Spastic CP patients aged between 2 and 6 years entered this study. At the first visit, Modified Ashworth scale for assessment of spasticity was used. Then Cerebrolysin was administered at a dose of 0.1 cc/kg intramuscularly (IM) for 3 months. In the first month, the medication was injected 5 times per week. In the second month of therapy, injections were performed as follows: 4 injections in the first week, 3 injections in the second week, 2 injections in the third week and a single one in the fourth week. In the third month of therapy, Cerebrolysin was continued as weekly injections. The spasticity of the patients was evaluated at the end of the first and third month of therapy. Results: Modified Ashworth score at baseline was 20.62 ± 9.65 which reached 15.19 ± 7.30 after 1 month of treatment. This figure was 14.81 ± 3.77 at month 3. Total decline in Modified Ashworth Scale was 5.42 ± 5.33 at the first month and 5.81 ± 2.74 at the third month in comparison to baseline. The difference between Modified Ashworth Scale at baseline and 1 month after therapy was significant (P = 0.000) but there was no significant difference between first month and third month of therapy. (P = 0.755). Also analysis indicates that there was an association between absolute reduction of Modified Ashworth score and the age at beginning of treatment (P = 0.037). Conclusions: Using Cerebrolysin as a neurotrophic peptide may improve spasticity of children with CP and should be considered as a possible useful treatment in CP cases.
Motor benefit from levodopa in spastic quadriplegic cerebral palsy
AbstractWe report on a 16-year-old girl with spastic quadriplegic cerebral palsy associated with premature birth and typical periventricular leukomalacia, who had a dramatic improvement in motor function after treatment with carbidopa/levodopa. Kinematic and electromyographic analyses of reaching movements demonstrate that levodopa decreased muscle co-contraction, decreased unwanted movements, and improved her ability to maintain a steady arm posture. These findings suggest that levodopa be considered as an adjunct therapy for the treatment of spastic quadriplegic cerebral palsy. Ann Neurol 2000;47:662–665
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.
