DeCure for Intellectual disability-hypotonia-spasticity-sleep disorder syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intellectual disability-hypotonia-spasticity-sleep disorder syndrome — 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 moduleIntellectual disability-hypotonia-spasticity-sleep disorder syndrome 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 intellectual disability-hypotonia-spasticity-sleep disorder syndrome 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
ankyrin 3 (ANK3) — ANK3 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4O6X · 2.103 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Three children with Prader-Willi syndrome, a rare genetic disease that includes hypotonia, hyperphagia, sleepiness and cognitive defects, were given pitolisant, a histamine 3 receptor inverse agonist approved for narcolepsy. In this case series, the drug was reported to decrease daytime sleepiness and improve cognition, with faster processing speed and better mental clarity. No sample size beyond three patients is given, and no control group is mentioned. The report is from 2019 and has not been followed by a larger trial.
A 2021 review notes that sleep disorders are common in adults with intellectual disabilities but are often overlooked or considered difficult to treat. The evidence base for managing these sleep disorders in this population is limited, and the authors call for collaborative work between psychiatrists and sleep specialists. No specific drug or intervention is tested in that paper.
A 2022 paper argues that in children with intellectual or developmental disabilities, sleep disorders such as restless sleep, restless legs syndrome, and sleep-disordered breathing are underdiagnosed. It states that central iron deficiency, often worsened by vitamin D deficiency, underlies much hypermotor restlessness. The paper recommends routine blood tests for ferritin, transferrin, vitamin D, and C-reactive protein, and claims that treating sleep-disordered breathing, restless legs syndrome, and restless sleep disorder improves daytime behaviour and cognition in children with intellectual disabilities. No new patient data are presented.
What is missing is any controlled trial of pitolisant in intellectual disability-hypotonia-spasticity-sleep disorder syndrome specifically. The pitolisant evidence is limited to three children with Prader-Willi syndrome, a different condition. No funding for a larger trial is reported, no trial design has been published, and no patient stratification by iron or vitamin D status has been tested in this syndrome.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Pediatric Pharmacology and Therapeutics · 2019 · 37 citations · open access
Cognitive Improvements in Children with Prader-Willi Syndrome Following Pitolisant Treatment—Patient Reports
AbstractWhile children with Prader-Willi Syndrome (PWS), a rare genetic disease with an incidence of 1:15,000, typically present with hypotonia and hyperphagia, their lives are made more difficult by an ever-present sleepiness as well as multiple neuro-cognitive dysfunctions, including cognitive defects. We describe a case series of 3 children who were treated with the histamine 3 receptor inverse agonist pitolisant. While this first-in-class inverse agonist is approved for another orphan disease (i.e., narcolepsy with or without cataplexy), we have observed that pediatric patients with PWS prescribed pitolisant demonstrate decreased daytime sleepiness and improved cognition, as evidenced by increased processing speed and improved mental clarity. Pitolisant may represent a novel therapeutic option that might relieve substantial PWS disease burden, including cognitive disability, excessive daytime sleepiness, and poor-quality nighttime sleep.
BJPsych Bulletin · 2021 · 14 citations · open access
Sleep: the neglected life factor in adults with intellectual disabilities
AbstractSleep is vital for our physical and mental health. Studies have shown that there is a high prevalence of sleep disorders and sleep difficulties amongst adults with intellectual disabilities. Despite this, sleep is often overlooked or its disorders are considered to be difficult to treat in adults with intellectual disabilities. There is a significant amount of research and guidance on management of sleep disorders in the general population. However, the evidence base for sleep disorders in adults with intellectual disabilities is limited. In this review paper, we look at the current evidence base for sleep disorders in adults with an intellectual disability, discuss collaborative working between intellectual disabilities psychiatrists and sleep medicine specialists to manage sleep disorders, and provide recommendations for future directions.
Image_1_Behavioral sleep medicine—The need for harmonization of clinical best practice outcome measures in children and adolescents with intellectual or developmental disabilities and restless sleep.pdf
Abstract<p>In behavioral medicine, sleep disorders, insomnia in particular, may be considered comorbidities and precipitating factors to intellectual or developmental disabilities (IDD). Nevertheless, sleep alterations have often been neglected in favor of daytime features and symptoms, albeit simple behavioral nighttime observations may disclose hypermotor features that characterize restless sleep. The root of most hypermotor restlessness is linked to central iron deficiency. The latter is often exacerbated by vitamin D deficiency (VDD), which interferes with both dopaminergic and serotonergic mechanisms. In this way, an imbalance affecting daytime behavior and mood is created. Several sleep-related motor disorders such as bruxism, periodic and aperiodic leg movements, Restless Legs Syndrome (RLS), and Restless Sleep Disorder (RSD) are commonly seen in Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD). However, they are rarely diagnosed and often overlooked in affected children and adolescents. As a result, not only are these disorders not adequately addressed therapeutically, but their symptoms may be worsened by the side-effects of drugs used to contain disruptive daytime behavior, such as antipsychotics and antidepressants. In children with IDDs, obesity, inactivity and metabolic effects of antipsychotics often lead to Sleep Disordered Breathing (SDB), which is currently understood as an inflammatory state leading to “hyperactive” lethargy and further alterations of the hypoxic chain and vitamin D levels. Endorsing simple routine blood tests, including inflammatory markers such as C-reactive protein, ferritin, transferrin, and vitamin D levels, may favorably complement caregiver observations and ambulatory sleep recordings, leading to a sleep disorder diagnosis and consequent therapy. In fact, the treatment of SDB, RLS, and RSD has been copiously demonstrated to favorably impact vigilance, behavior, social competence, and academic skills in healthy and, to a greater extent, in IDD children. Thus, consulting and deliberating the root causes of functional and categorical diagnoses within a clinical framework may engender a more precise diagnosis and further benefit pediatric daytime and nighttime management of hyperactive behaviors.</p>
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.
