DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for CHARGE syndrome — screening already-approved drugs against its 11-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCHARGE syndrome maps to a 11-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 charge 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
lysine demethylase 6A (KDM6A) — KDM6A 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 e7zdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6FUL · 1.649 Å · ligand 1-methyl-5-oxidanyl-4-oxidanylidene-pyridine-2-carboxylic acid (E7Z). Experimental structure, not a prediction.
What the evidence adds up to
CHARGE syndrome is a multiple congenital anomaly condition caused, in a majority of individuals, by loss-of-function pathogenic variants in the gene CHD7 on chromosome 8. The acronym stands for coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, and ear anomalies or deafness. Between 80% and 90% of individuals meet the qualifications for deaf-blindness even when the hearing or vision impairment is mild. Intellectual disabilities are not as common as early research indicated; cognitive functioning ranges widely, and some contend that intelligence is often underestimated due to communication barriers or inappropriate assessments.
No drug treatment for CHARGE syndrome itself is described in any of these abstracts. The 2017 special issue summarises advances in animal models (mice, zebrafish, flies, frog) and cell-based systems developed since 2004 to explore underlying pathophysiology, but no therapeutic trial is reported. The 2020 paper presents two new CHD7 gene mutations and suggests that missense mutations may be associated with milder clinical expression whereas truncating mutations may be associated with more severe expression, but notes that in the scientific literature to date there is no clear genotype-phenotype correlation.
Behavioural challenges are prevalent and distinct, more frequent than expected compared to others with deaf-blindness or similar syndromes. Causes cited include communication difficulties, sensory impairments, balance problems, medical discomfort, stress, anxiety, and executive dysfunction. One 2017 study investigates positive behaviour support strategies for young adults who are deafblind, including those with CHARGE, but does not report quantitative outcomes such as reduction in problem behaviours or sample sizes. The authors state that behaviour interventions should incorporate recognising the cause of behaviours, reducing stress and discomfort, and accounting for sensory impairments.
What is still missing is any clinical trial of a pharmacological intervention for CHARGE syndrome, any drug repurposing data, and any systematic behavioural intervention study with reported effect sizes. The field lacks funded trials, validated outcome measures for the syndrome’s core features, and patient stratification beyond the emerging genotype-phenotype suggestion.
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 C Seminars in Medical Genetics · 2017 · 80 citations · open access
New insights and advances in CHARGE syndrome: Diagnosis, etiologies, treatments, and research discoveries
AbstractCHARGE syndrome is a multiple congenital anomaly condition caused, in a majority of individuals, by loss of function pathogenic variants in the gene CHD7. In this special issue of the American Journal of Medical Genetics part C, authors of eleven manuscripts describe specific organ system features of CHARGE syndrome, with a focus on recent developments in diagnosis, etiologies, and treatments. Since 2004, when CHD7 was identified as the major causative gene in CHARGE, several animal models (mice, zebrafish, flies, and frog) and cell-based systems have been developed to explore the underlying pathophysiology of this condition. In this article, we summarize those advances, highlight opportunities for new discoveries, and encourage readers to explore specific organ systems in more detail in each individual article. We hope the excitement around innovative research and development in CHARGE syndrome will encourage others to join this effort, and will stimulate other investigators and professionals to engage with individuals diagnosed as having CHARGE syndrome, their families, and their care providers.
AbstractCHARGE syndrome is a condition that has historically been diagnosed on the basis of the clinical findings of coloboma, heart disease, choanal atresia, restricted growth, and/or central nervous system anomalies, genital hypoplasia, and ear anomalies and/or deafness. Recently, researchers have discovered a genetic link, specifically, a strong association between the CHARGE phenotype and a mutation of the CHD 7 gene on the long arm of chromosome 8. Diagnosis now can be confirmed but not excluded with a positive mutation of this gene. This article offers an explanation of the diagnostic process as well as a description of the physical assessment and corresponding clinical implications of CHARGE syndrome in the neonatal population.
Korean Journal of Ophthalmology · 1998 · 8 citations
Clinical characteristics of CHARGE syndrome
AbstractCHARGE syndrome, first described by Pagon, was named for its six major clinical features. They are: coloboma of the eye, heart defects, atresia of the choanae, retarded growth and development including CNS anomalies, genital hypoplasia and/or urinary tract anomalies, and ear anomalies and/or hearing loss. We experienced three cases of CHARGE syndrome who displayed ocular coloboma, heart defects, retarded growth and development, and external ear anomalies, and we also review the previously reported literature concerning CHARGE syndrome.
Positive Behavior Supports for a Young Adult with CHARGE Syndrome
AbstractCHARGE is a multifaceted syndrome, so named for a collection of characteristics commonly exhibited by individuals with this genetic condition. The acronym CHARGE stands for coloboma, heart defects, atresia choanae, retarded growth and development, genital hypoplasia, and ear anomalies and deafness (Blake, Salem-Hartshorne, Daoud, & Gradstein, 2005). Although individuals with CHARGE may not exhibit all of these traits, most--between 80% and 90%--meet the qualifications for deaf-blindness even when the hearing or vision impairment is mild (Hartshorne, Hefner, Davenport, & Thelin, 2011). Intellectual disabilities, however, are not as common in this population as early research indicated (Graham, Rosner, Dykens, & Visootsak, 2005). Those with CHARGE syndrome have a wide range of cognitive functioning, and some contend that intelligence is often underestimated due to communication barriers or the use of inappropriate assessments (Hartshorne et al., 2011). Furthermore, CHARGE syndrome is often associated with conditions such as obsessive-compulsive disorder, autism spectrum disorder, attention deficits, tic disorders or Tourette syndrome, anxiety, and executive dysfunction (Blake et al., 2005; Hartshorne et al., 2011; Hartshorne, Nicholas, Grialou, & Russ, 2007). In addition to these concomitant conditions, communication is often a challenge related to CHARGE. Some children with CHARGE develop symbolic communication, whereas others do not (Thelin & Fussner, 2005). Most experts attribute delayed or lack of language development to the sensory impairments associated with CHARGE (Graham et al., 2005; van Dijk & de Kort, 2005). Those who do develop symbolic communication most likely use total communication (the pairing of spoken and signed languages; Thelin & Fussner, 2005) and are prone to idiosyncratic communication patterns (van Dijk & de Kort, 2005). Communication skills are imperative for social and educational outcomes as well as for self-regulation (Kennert, Ramirez, Hartshorne, Deuce, & Nicholas, 2015). Closely related to issues of communication are behavioral challenges that are prevalent with CHARGE syndrome. Problematic behaviors are often attributed to communication difficulties, and as Hartshorne and colleagues (2011) note, behaviors are communication. Behaviors exhibited by individuals with CHARGE are distinct and more frequent than expected when compared to others with deaf-blindness or similar syndromes (Graham et al., 2005; Hartshorne et al., 2011). Beyond communication difficulties, other causes cited for challenging behaviors include sensory impairments, responses to or lack of control over environments, balance and equilibrium problems, medical issues and discomfort, stress and anxiety, and executive dysfunction (Blake et al., 2005; Graham et al., 2005; Hartshorne et al., 2007, 2011; van Dijk & de Kort, 2005). Experts say that behavior interventions for individuals with CHARGE syndrome should incorporate three key features: recognizing the cause of behaviors; reducing stress, anxiety, and discomfort; and accounting for sensory impairments (Blake et al., 2005; Graham et al., 2005; van Dijk & de Kort, 2005). These priorities align well with the positive behavior support model. Recognizing that challenging behaviors lead to exclusion and isolation, positive behavior support aims to reduce problematic behaviors to improve quality of life (Horner, 2000). Positive behavior support utilizes functional behavior analysis to understand the cause of inappropriate behaviors and then addresses issues in an individual's environments because [t]he assumption is not that individuals are defective or broken, but that they experience the world around them in a way that is different from their peers (Horner, 2000, p. 99). The present study investigates the use of positive behavior support strategies with young adults who are deafblind, including those with CHARGE syndrome, to determine which are effective for preventing or stopping problem behaviors. …
Saudi Journal of Ophthalmology · 2020 · 1 citations · open access
CHARGE syndrome
AbstractCHARGE syndrome is a genetic disorder comprising the following clinical features: coloboma, heart defects, choanal atresia, retardation (of growth and development), as well as genitourinary and ear abnormalities. This syndrome is caused by mutations in the CDH7 gene, located on chromosome 8 (8q12). We present two new gene mutations in two patients with CHARGE syndrome, not previously reported in the scientific literature. Both of these patients clearly demonstrate the difference in the clinical expression of this syndrome, with patient 1 having a greater clinical severity compared to patient 2. We conclude that although in the scientific literature to date there is no clear correlation between a patient's genotype and phenotype expression, we can assume from the cases we present that a correlation does in fact exist. Specifically, missense mutations (as in case of patient 2) are associated with milder clinical expression, whereas mutations which result in truncation of the CDH7 protein (as in the case of patient 1 having a nonsense mutation) may be associated with a more severe clinical expression.
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.
