DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for alternating hemiplegia of childhood — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAlternating hemiplegia of childhood maps to a 12-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 alternating hemiplegia of childhood 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
nuclear receptor subfamily 0 group B member 1 (NR0B1) — NR0B1 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 2sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4RWV · 1.859 Å · ligand (2S)-3-{[(R)-{[(1S,2S,3R,4S,5S,6S)-2,6-dihydroxy-3,4,5-tris(phosphonooxy)cyclohexyl]oxy}(hydroxy)phosphoryl]oxy}propane
-1,2-diyl dihexadecanoate (PIZ). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 case report describes a 14-year-old female with alternating hemiplegia of childhood who did not respond to haloperidol, flunarizine, or propranolol. Treatment with aripiprazole reduced the frequency, duration, and severity of hemiplegic episodes. When the patient was inadvertently given an inactive drug, her episodes worsened, then improved again on rechallenge with aripiprazole. The report is a single case with no control, no blinding, and no replication.
The genetic basis of alternating hemiplegia of childhood was established by 2013, when heterozygous de novo mutations in the ATP1A3 gene were identified as the cause. The disorder is almost exclusively sporadic, with only a few cases of concordance in monozygotic twins and dominant transmission in families with a milder phenotype. A 2022 case report confirms that genetic testing now allows diagnosis in young children: a 3-year-old male who presented with frequent falls and gait abnormality, and had been treated for seizure disorder since 5 months of age, was diagnosed with AHC after genetic testing.
A 1972 review (the abstract is in Japanese but the English portion states) that no cure is available and that flunarizine is the most commonly used drug for reducing the frequency and intensity of paroxysmal events. The same abstract notes that mutations in ATP1A2 and particularly ATP1A3 are the main genes responsible, and that the term ATP1A3 syndrome now encompasses a range of disorders including rapid-onset dystonia-parkinsonism, cerebellar ataxia, early infant epileptic encephalopathy, and fever-induced paroxysmal weakness and encephalopathy.
What is still missing: no controlled trials of aripiprazole or any other drug for AHC exist; the evidence rests on single case reports and clinical experience with flunarizine. No trial has stratified patients by ATP1A3 mutation type, and no funding for a multi-centre randomised trial has been reported. The natural history and genotype-phenotype correlations remain incompletely mapped.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Developmental Medicine & Child Neurology · 2008 · 21 citations · open access
Treatment of alternating hemiplegia of childhood with aripiprazole
AbstractWe report the pharmacological treatment of a case of alternating hemiplegia of childhood (AHC) in a 14-year-old female with an established diagnosis. Although the patient's symptoms are consistent with those of the condition, she did not respond to treatment with haloperidol, flunarizine, or propranolol. Treatment with aripiprazole resulted in a reduction in the frequency, duration, and severity of episodes of alternating hemiplegia, along with other therapeutic benefits. After treatment with aripiprazole was started, the patient was inadvertently given an inactive drug, resulting in a worsening of her hemiplegic episodes, which improved again on rechallenge. A comparison of the pharmacological actions of successful and unsuccessful treatments for AHC is made. Modulation of both dopamine and histamine systems together appears to be important in the treatment of AHC and further investigation of such pharmacotherapies is suggested.
Journal of Pediatric Neurology · 2015 · 2 citations
Alternating hemiplegia of childhood
AbstractWe reviewed the etiologic aspects, clinical symptoms, complementary studies, differential diagnosis and treatment of alternating hemiplegia of childhood (AHC). AHC is an uncommon illness of uncertain pathophysiology that provokes crisis of transient hemiplegia affecting one hemibody or occasionally both at the same time. Clinical symptoms of AHC usually begin before the age of 18 months and in some cases may present in the neonatal period. Clinical symptoms include abnormal ocular movements such as nystagmus and dystonic or tonic posturing. Hemiplegic attacks are not associated with alteration of consciousness. Hemiplegia may disappear after arousal and may reappear 10 to 20 minutes after arousal in children with AHC. The diagnosis of AHC is clinically made, and most of the clinically used diagnostic tests result in negative. The treatment of AHC includes flunarizine. It is necessary to suspect this diagnosis to identify patients with AHC.
Alternating hemiplegia of childhood is caused by heterozygous de novo mutations in the ATP1A3 gene: The expanding mutational spectrum of ATP1A3-related dystonic movement disorders
AbstractAims: Alternating hemiplegia of childhood (AHC) is a rare neurological disorder characterized by early onset of hemiplegic episodes, dystonia, and developmental impairment. Besides few cases of concordance in monozygotic twins and dominant transmission in families with milder phenotype, AHC is almost exclusively sporadic. The aim of the study is to identify de novo mutations associated with the disease.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · 2022 · 0 citations · open access
Frequent Fall: Seizure or Weakness? A Case Report of Alternating Hemiplegia of Childhood
AbstractAlternating Hemiplegia of Childhood (AHC) is a complex disease which causes recurrent hemiplegic attacks. Although ATP1A3 gene has been identified as the cause of this neurological entity, many variants are being reported nowadays, adding to the spectrum of ATP1A3 gene-related disorders due to the advancement in genetic testing. Hereby, authors presents a case report of a 3-year-old male child who presented with a complaint of frequent falls while walking with gait abnormality and has been on treatment for seizure disorder since, 5 months of age. On assessing the history and evaluating the child, AHC was suspected and the same was confirmed using genetic tests.
AbstractAlternating Hemiplegia of Childhood (AHC) is a rare disorder with onset in the first 18 months of life characterized by stereotyped paroxysmal manifestations of tonic and dystonic attacks, nystagmus with other oculomotor abnormalities, respiratory and autonomic dysfunctions. AHC is often associated with epileptic seizures and developmental delay. Hemiplegic paroxysm is the most remarkable symptom, although AHC includes a large series of clinical manifestations that interfere with the disease course. No cure is available and the treatment involves many specialists and therapies. Flunarizine is the most commonly used drug for reducing the frequency and intensity of paroxysmal events. Mutations in ATP1A2, particularly in ATP1A3, are the main genes responsible for AHC. Some disorders caused by ATP1A3 variants have been defined as ATP1A3-related disorders, including rapid-onset dystonia-parkinsonism, cerebellar ataxia, pes cavus, optic atrophy, sensorineural hearing loss, early infant epileptic encephalopathy, child rapid-onset ataxia, and relapsing encephalopathy with cerebellar ataxia. Recently, the term ATP1A3 syndrome has been identified as a fever-induced paroxysmal weakness and encephalopathy, slowly progressive cerebellar ataxia, childhood-onset schizophrenia/autistic spectrum disorder, paroxysmal dyskinesia, cerebral palsy/spastic paraparesis, dystonia, dysmorphism, encephalopathy, MRI abnormalities without hemiplegia, and congenital hydrocephalus. Herewith, we discussed about historical annotations of AHC, symptoms, signs and associated morbidities, diagnosis and differential diagnosis, treatment, prognosis, and genetics. We also reported on the ATP1A3-related disorders and ATP1A3 syndrome, as 2 recently established and expanded genetic clinical entities.
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.
