DeCure for Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies
DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies — 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 developmental disorder with hypotonia, impaired speech, and dysmorphic facies 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 developmental disorder with hypotonia, impaired speech, and dysmorphic facies 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.
What the evidence adds up to
Two siblings with a novel homozygous TBCK mutation (c.1854delT) presented with severe intellectual disability, no speech, hypotonia, convulsions, and complete dependence for daily skills. Elevated beta-HCG in maternal serum during both pregnancies was noted, a finding not previously reported. The 2016 study describes a severe, nonspecific neurodevelopmental disorder with very poor psychomotor development and inability to walk independently.
A separate 2017 report describes a male patient with Potocki-Lupski syndrome, a different genetic condition caused by a 17p12-p11.2 duplication. He showed speech and borderline cognitive delay with behavioural troubles but no autism features. By age five, speech skills had noticeably improved and scholastic performance was moderate. The authors note that Potocki-Lupski syndrome can range from mild behavioural disturbances to severe autism.
A third abstract reviews 33 previously reported cases of TBCK-related disorder, now called infantile hypotonia with psychomotor retardation and characteristic facies-3 (IHPRF3). Two sisters with a novel TBCK mutation (c.753dup; p.(Lys252*)) are added. The review concludes that TBCK mutations cause a progressive neurodegenerative disease with predominant central nervous system involvement. No treatment or intervention is discussed in any of these abstracts.
What remains missing is any understanding of the pathogenesis of TBCK mutations, any preclinical model or drug screening data, and any clinical trial design or patient stratification strategy. No drug is mentioned in any of these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Medical Genetics Part A · 2016 · 19 citations
TBCK‐related intellectual disability syndrome: Case study of two patients
Journal of Pediatric Genetics · 2017 · 18 citations · open access
A New Patient with Potocki–Lupski Syndrome: A Literature Review
AbstractSpeech delay, intellectual disability, and behavioral disturbances are the main clinical manifestations of Potocki-Lupski syndrome. Other features include infantile hypotonia, the absence of major dysmorphism, sleep disorders, and congenital anomalies, particularly of the cardiovascular system. A male patient with Potocki-Lupski syndrome is reported herein. He showed speech and borderline cognitive delay, behavioral troubles with no signs suggestive of autism, in the absence of major dysmorphism. A de novo 17p12-p11.2 duplication spanning 3.6 Mb was detected, with boundaries from 15,284,052 to 18,647,233 (hg19 assembly). At the age of 5 years, the child showed a noticeable improvement of speech skills and a moderate scholastic performance was reached. Upon analysis of the clinical manifestations of the present patient and those reported in existing literature, we found that the syndrome may present in various degrees of clinical expressivity. Affected patients may manifest symptoms ranging from mild behavioral disturbances to severe degrees of autism.
Revista de estudios locales. Cunal · 1997 · 0 citations
Las funciones reservadas a los funcionarios locales con habilitación de carácter nacional.
AbstractDeleterious homozygous or compound heterozygous mutations in the TBCK (TBC1-domain-containing kinase) gene (implicated in the MTOR pathway) produce profound hypotonia, global developmental delay, facial dysmorphic features, and brain abnormalities. The disorder has been named "infantile hypotonia with psychomotor retardation and characteristic facies-3" (IHPRF3). Here we present two sisters with a novel mutation in TBCK (NM_001163435.2: c.753dup; p.(Lys252*)) who have this ultrarare disorder. We have reviewed the literature on the 33 previously reported cases to provide a characterization of this emerging phenotype. Pathogenic mutations in TBCK have a predominant involvement of the Central Nervous System with a progressive pattern, leading to the conclusion where pathogenic mutations of the said gene lead to a progressive neurodegenerative disease. This report adds novel mutation and features to this complex phenotype. Further investigation is required to understand the pathogenesis of TBCK.
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.
