5.15 drug treatment of irritability, aggression, agitation, and self-injurious behavior in fragile x syndrome: a large-scale cross-sectional analysis
Behavioral dysregulation is a key manifestation of the fragile X syndrome (FXS) phenotype, often presenting out-of-proportion to the individual ’s cognitive level. One common behavioral cluster noted in individuals with FXS—particularly in males—is irritability, agitation, aggression, and self-injurious (IAAS) behaviors estimated to occur in at least 50 percent of individuals. Despite this significant level of patient and caregiver bu rden attributable to IAAS behaviors and the relatively high proportion of individuals with FXS who exhibit these traits, there remains limited large-scale information concerning the psychopharmacologic management of IAAS to help guide future treatment.
The U.S. Patent and Trademark Office has issued a patent to Zynerba Pharmaceuticals for the company ’s lead new drug candidate, a synthetic cannabidiol medicine. The patent, which expires in 2038, expands the Devon company’s intellectual property portfolio covering the experimental therapy called Zygel, which is formulated as a gel that is applied to the skin. Cannabidiol is a compound found in cannabis plants. Zygel is in late-stage clinical testing as potential treatment for fragile X syndrome.…
Authors: D'Antoni S, de Bari L, Valenti D, Borro M, Bonaccorso CM, Simmaco M, Vacca RA, Catania MV Abstract Impaired energy metabolism may play a role in the pathogenesis of neurodevelopmental disorders including fragile X syndrome (FXS). We checked brain energy status and some aspects of cell bioenergetics, namely the activity of key glycolytic enzymes, glycerol-3-phosphate shuttle and mitochondrial respiratory chain (MRC) complexes, in the cerebral cortex of the Fmr1 knockout (KO) mouse model of FXS. We found that, despite a hyperactivation of MRC complexes, adenosine triphosphate (ATP) production via mitochondri...
ConclusionThese results support the expansion of FXS screening criteria in guidelines.
Conclusion: This randomized controlled trial of sertraline treatment showed no benefit with respect to primary or secondary outcome measures. For the 6-month period, treatment in young children with ASD appears safe, although the long-term side effects of low-dose sertraline in early childhood are unknown.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT02385799.
CONCLUSIONS: Our results demonstrate that sound exposure, but not attenuation, during early developmental window restores molecular, cellular and functional properties in the auditory cortex of Fmr1 KO mice, and suggest this approach as a potential treatment for sensory phenotypes in FXS. PMID: 31698054 [PubMed - as supplied by publisher]
CONCLUSION: In this concise review, we summarize and analyze the main hypotheses proposed to explain synaptic dysregulation in FXS, by reviewing the scientific evidence that led to pharmaceutical clinical trials and their outcome. PMID: 31682210 [PubMed - as supplied by publisher]
The investment will be used to build a clinical-stage portfolio for rare diseases, including treatments for Fragile X syndrome.
ConclusionsFindings from this investigation strongly suggest that the PPVT-III should not be used as a screening tool for language levels or cognitive function in clinical studies since the scores from the PPVT-III were not representative of global language or non-verbal cognitive skills in adults with intellectual disabilities. This finding is critical in order to understand how to evaluate, as well as to treat, language in individuals with FXS. Development of efficient and appropriate tools to measure language, cognition, and behavior in individuals with FXS is essential.
This article suggests that systems biology, emphasizing the epigenetic component of systems biology, could help identify clinically useful biomarkers in neuropsychiatric disorders like SZ, BD, and MDD.
Abstract Expansions of simple trinucleotide repeats, such as (CGG)n, (CAG)n or (GAA)n, are responsible for more than 40 hereditary disorders in humans including fragile X syndrome, Huntington's disease, myotonic dystrophy, and Friedreich's ataxia. While the mechanisms of repeat expansions were intensively studied for over two decades, the final picture has yet to emerge. It was important, therefore, to develop a mammalian experimental system for studying repeat instability, which would recapitulate repeat instability observed in human pedigrees. Here, we describe a genetically tractable experimental system to stud...