Fragile X Syndrome

The purpose of this Phase IIa study is to evaluate the safety, tolerability, and effectiveness of CTH120 in adult males with Fragile X syndrome.

This study is a multicenter, double-blind, randomized, placebo-controlled study to assess the safety and tolerability of 3 doses of MRM-3379 in male participants with Fragile X Syndrome ages 16 to 45 (inclusive). In addition, a parallel cohort of participants ages 13 to \<16 will receive open-label MRM-3379. All participants will participate for 12 weeks of treatment. The study is also intended as a proof-of-concept investigation to evaluate whether MRM-3379 can improve FXS symptoms

Cell-free fetal DNA (cffDNA) is present in the maternal blood from the early first trimester of gestation and makes up 5%-20% of the total circulating cell-free DNA (cfDNA) in maternal plasma. Its presence in maternal plasma has allowed development of noninvasive prenatal diagnosis for single-gene disorders (SGD-NIPD). This can be performed from 9 weeks of amenorrhea and offers an early, safe and accurate definitive diagnosis without the miscarriage risk associated with invasive procedures. One of the major difficulties is distinguishing fetal genotype in the high background of maternal cfDNA, which leads to several technical and analytical challenges. Besides, unlike noninvasive prenatal testing for aneuploidy, NIPD for monogenic diseases represent a smaller market opportunity, and many cases must be provided on a bespoke, patient- or disease-specific basis. As a result, implementation of SGD-NIPD remained sparse, with most testing being delivered in a research setting. The present project aims to take advantage of the unique French collaborative network to make SGD-NIPD possible for theoretically any monogenic disorder and any family.

Fragile X Syndrome (FXS) is a complex neurodevelopmental disorder caused by a mutation on the X chromosome. Scientists have investigated FXS extensively in both humans and animals. Thus far, phenotypic rescue in animal models has not resulted in treatment breakthroughs in humans, though some important discoveries have been made. Research has shown that individuals with FXS process sounds differently than those in the typical population, and they also show baseline differences in brain activity, including high gamma activity, increased theta activity, and decreased alpha activity. The investigators' central hypothesis is that these alterations in brain activity (specifically alpha and gamma activity) impair the brain's ability to process new information, thereby impeding cognitive functioning and increasing sensory sensitivity. The investigators propose that auditory entrainment, a technique that involves playing special sounds through headphones, will normalize brain activity in individuals with FXS and lead to increased cognitive function and decreased sensory hypersensitivity.

Individuals with Fragile X Syndrome show differences in how they understand and learn language from infancy. They frequently have lifelong delays in speech and language as well. In addition, they experience other auditory symptoms, including being very sensitive to certain sounds as well as being more sensitive than others to loud sounds. The underlying brain activity for sound perception and speech learning in Fragile X is not well understood, especially in the infant and toddler years. This study uses behavioral assessment of speech and language abilities, neuroimaging, and hearing tests to understand how speech and hearing are different in children with Fragile X Syndrome.

The goal of this study is to identify which brain regions are active during speech-in-noise perception, as well as how those regions interact. The investigators are studying brain activation during speech-in-noise in autism and controls as well as individuals with Fragile X Syndrome. The main question\[s\] it aims to answer are: 1) How does the brain's response to background noise affect a person's ability to understand speech? 2) Can visual cues improve hearing in background noise? Participants will complete the following: * hearing tests * cognitive and behavioral measures * questionnaires about their symptoms * both passive and active hearing tasks while brain activity is recorded with a neuroimaging cap Results will be compared between individuals with autism with and without Fragile X Syndrome as well as individuals without autism.

The purpose of this study is to investigate the Psychiatric and Cognitive Phenotypes in Velocardiofacial Syndrome (VCFS), Williams Syndrome (WS)and Fragile X Syndrome Characterization, Treatment and Examining the Connection to Developmental and Molecular Factors

Purpose: Conduct a wait-list randomized controlled trial (RCT) of an inclusive physical activity program called PACE for adults with intellectual disability (ID) who are not yet showing signs of Alzheimer's Disease (AD)/age-related dementias (ARD). Participants: Participants include 120 adults with ID, their caregivers, and their coaches (up to 360 individual participants, grouped as triads), recruited through the University of North Carolina at Chapel Hill and the University of Arkansas. Participants also include 16 exercise professionals. Procedures (methods): Each cohort will include 20 triads who are randomly assigned to the PACE program or the waitlist control group.

The purpose of this study is to evaluate the effectiveness of an adapted, telehealth functional behavioral therapy (FBTsIDD) specifically focused on promoting appropriate communication and behavioral strategies in individuals with syndromic intellectual and developmental disorders. Participants will be asked to complete virtual study assessments at intake and then on a monthly basis for the duration of 3-6 months. In addition, participants will attend weekly or biweekly virtual intervention visits with a study therapist.

There are currently no approved medications for the treatment of anxiety in children and youth with neurodevelopmental disorders (NDDs), both common and rare. Sertraline, a selective serotonin reuptake inhibitor, has extensive evidence to support its use in children's and youth with anxiety but not within NDDs. More research is needed to confirm whether or not sertraline could help improve anxiety in children and youth with common and rare neurodevelopmental conditions. This is a pilot study, in which we plan to estimate the effect size of reduction in anxiety of sertraline vs. placebo. across rare and common neurodevelopmental disorders, and determine the best measure(s) to be used as a primary transdiagnostic outcome measure of anxiety, as well as diagnosis specific measures in future, larger-scale clinical trials of anxiety in NDDs.

Individuals with Fragile X Syndrome show differences in how they understand and learn language from infancy. They frequently have lifelong delays in speech and language as well. In addition, they experience other auditory symptoms, including being very sensitive to certain sounds as well as being more sensitive than others to loud sounds. The underlying brain activity for sound perception and speech learning in Fragile X is not well understood, especially in the infant, toddler, and preschool years. This study uses behavioral assessment of speech and language abilities, neuroimaging, and hearing tests to understand how speech and hearing are different in children with Fragile X Syndrome.

This study is a controlled trial of metformin in children with fragile X syndrome(FXS). The age of FXS children range from 2 to 16 years old. Participants will be randomized in a double-blind design to either drug or placebo for 6-month period. The primary objectives are to assess metformin in treatment of behavior problems, cognitive and language with fragile X syndrome.

This proposal focuses on the therapeutic relevance of the endocannabinoid (eCB) system for the treatment of Fragile-X syndrome (FXS), the primary hereditary cause of autism spectrum disorder (ASD). Although most individuals with FXS have moderate to severe intellectual disability (ID), caregivers are mainly concerned about aggressive behavior and anxiety problems, hallmark features of the condition. Concurrent lines of evidence suggest that targeting the endocannabinoid (eCB) system by administration of cannabidiol (CBD) could upregulate GABAergic functions and correct inhibitory deficits presumed responsible for the neuropsychiatric phenotype of FXS. However, the eCB system and its effect on the brain remains unexplored in FXS patients. This clinical trial aims to define the therapeutic relevance of the eCB system for FXS using a multimodal neuroimaging approach to finely characterize the acute effects of oral CBD on the principal inhibitory neurotransmitter system (GABA) in a large cohort of FXS patients.

This study focuses on the therapeutic relevance of the endocannabinoid (eCB) system for the treatment of Fragile-X syndrome (FXS), the primary hereditary cause of autism spectrum disorder (ASD). Most individuals with FXS have moderate to severe intellectual disability (ID), and caregivers are mainly concerned about aggressive behavior and anxiety problems. Since FXS individuals have a normal lifespan, the overall lifetime cost for the Canadian society of a single case is estimated at $1.2 to $4.7 millions reaching $18 billions for all FXS cases. There is no cure for FXS, as all clinical trials so far have been unsuccessful.FXS is caused by transcriptional silencing of the Fragile X mental retardation protein (FMR1) gene, making FXS a simple model to study ASD and ID pathophysiological mechanisms. Of those, neuronal hyperexcitability is largely recognized as a core deficit in FXS, and a critical therapeutic target for the disorder. Using transcranial magnetic stimulation (TMS) in FXS patients, our team provided the first direct evidence of Gamma-aminobutyric acid (GABA) receptor a (GABAa) dysfunctions in humans with this disorder and showed that this inhibitory deficit is linked with cortical hyperexcitability (PMID: 31748507). Concurrent lines of evidence suggest that stimulation of the endocannabinoid (eCB) system with the administration of Cannabidiol (CBD) could upregulate GABAergic function and correct inhibitory deficits presumed responsible for the neuropsychiatric phenotype of FXS. CBD has been shown to increase GABA concentration levels in the brains of healthy individuals, an effect that could help correct the hyperexcitability typically found in FXS. Thus, this trial aims to define the therapeutic potential of the eCB system for FXS, by measuring the impacts of oral CBD administration on the principal inhibitory neurotransmitter system of FXS patients, and the severity of the clinical phenotype.