DeCure for Congenital contractures of the limbs and face, hypotonia, and developmental delay
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital contractures of the limbs and face, hypotonia, and developmental delay — 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 moduleCongenital contractures of the limbs and face, hypotonia, and developmental delay 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 congenital contractures of the limbs and face, hypotonia, and developmental delay 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
tRNA splicing endonuclease subunit 2 (TSEN2) — TSEN2 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 8HMZ · 2.9 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2022 case report describes a patient with CLIFAHDD syndrome (congenital contractures of limbs and face, hypotonia, and developmental delay) caused by a NALCN mutation who was treated with pyridostigmine. The patient had hypotonia and apnea episodes requiring resuscitation. After starting pyridostigmine, the authors observed a significant reduction in apnea episodes and slight psychomotor progress. Congenital myasthenic syndrome was initially suspected but later excluded; the report attempts to explain a possible mechanism for the improvement in a NALCN mutation patient. No other patients were treated, and the report does not provide quantitative data such as number of apnea events before and after treatment or any measure of developmental progress.
A 2019 study from Russia describes two patients with CLIFAHDD syndrome caused by heterozygous missense mutations in the NALCN gene (c.4355T>C and c.3541C>G). The paper discusses the clinical features and approaches to differential diagnosis with monogenic distal arthrogryposis but reports no treatment outcomes or interventions. A 1997 report describes two brothers with macrocephaly, facial abnormalities, disproportionate tall stature, and mental retardation who were hypotonic neonatally and had developmental delay, but this predates the identification of NALCN mutations and does not involve CLIFAHDD syndrome or any drug treatment.
The evidence for pyridostigmine in CLIFAHDD syndrome rests on a single uncontrolled case report with no numerical outcomes. What is missing is any controlled trial, any replication in additional patients, any standardised measure of respiratory or motor function, and any understanding of which NALCN mutations might respond. Funding for natural history studies and genotype-stratified trials of cholinergic agents in NALCN-related disorders is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
International Journal of Environmental Research and Public Health · 2022 · 7 citations · open access
Central Apneas Due to the CLIFAHDD Syndrome Successfully Treated with Pyridostigmine
AbstractNALCN mutations lead to complex neurodevelopmental syndromes, including infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) and congenital contractures of limbs and face, hypotonia, and developmental delay (CLIFAHDD), which are recessively and dominantly inherited, respectively. We present a patient in whom congenital myasthenic syndrome (CMS) was suspected due to the occurrence of hypotonia and apnea episodes requiring resuscitation. For this reason, treatment with pyridostigmine was introduced. After starting the treatment, a significant improvement was observed in reducing the apnea episodes and slight psychomotor progress. In the course of further diagnostics, CMS was excluded, and CLIFAHDD syndrome was confirmed. Thus, we try to explain a possible mechanism of clinical improvement after the introduction of treatment with pyridostigmine in a patient with a mutation in the NALCN gene.
Neuromuscular Diseases · 2019 · 2 citations · open access
Clinical and genetic characteristics of the syndrome of contractures of the limbs and face, hypothony and psychomotor retardation (OMIM: 616 266), caused by mutations in the NALCN gene
AbstractA description of the clinical and genetic characteristics of the syndrome of congenital contractures of the limbs and face in combination with muscular hypotonia and psychomotor retardation of 2 patients from Russia is presented. As a result of full-exome DNA sequencing, 2 heterozygous missense mutations c 4355T C and c.3541C G were found in the NALCN gene, leading to amino acid substitutions at the functionally important center of the protein molecule. The effect of identified mutations in the NALCN gene on the function of its protein and approaches to the differential diagnosis of congenital contracture syndrome of the extremities and face in combination with muscular hypotonia and psychomotor retardation with monogenic variants of distal arthrogryposis with autosomal dominant type of inheritance are discussed.
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.
