Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome

Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation funded during 2014-2015, Dr. Frank Kooy and colleagues at the University of Antwerp are conducting a double blind crossover trial of ganaxolone in patients with Fragile X syndrome. Results of this study were mixed (see Marinus: Results from Phase 2 Exploratory Clinical Study Support Continued Development of Ganaxolone in Fragile X Syndrome.

Read more

GABA-A Receptor in Fragile X Syndrome

GABA-A Receptor in Fragile X Syndrome
FRAXA Research Foundation funded studies under the direction of Dr. Frank Kooy at the University of Antwerp in Belgium. $210,000 GrantsFrank Kooy, PhD Principal Investigator University of Antwerp, Belgium FRAXA Research Grants $45,000 in 2010 $100,000 in 2007-8 $65,000 in 1999-2000 by Frank Kooy, PhD Absence of a single protein, FMRP, in Fragile X patients leads to a cascade of molecular events in brain cells. To find out which other genes are involved the clinical symptoms, we have been looking for genes that are differentially expressed in Fragile X syndrome. One of the genes specifically underexpressed is part of the GABAA receptor. As GABA-A receptors are the main inhibitory receptors in the brain, involved in processes like anxiety, mood swings, sleep and cognition, processes also disturbed in Fragile X patients, we followed up on this finding. In subsequent studies, we demonstrated abnormalities in expression levels of multiple parts of the GABA-ARead more

Development of a Novel GABA-A Agonist in Fragile X Syndrome

Development of a Novel GABA-A Agonist in Fragile X Syndrome

Of the many genes known to be regulated by FMRP, the gamma-aminobutyric acid receptor A (GABA(A)), is gaining attention as a potential target for the treatment of FXS. Mounting evidence suggests decreased expression and functioning of GABA(A) is involved in the pathophysiology of FXS. Non-selective GABA(A) agonism in animal models of FXS has been associated with normalization of morphological features, GABA(A) expression, and behavior. However, the clinical use of these agents in Fragile X is associated with unwanted side-effects, such as sedation, dulling of cognition, and occasional paradoxical agitation, which limits their use. Given the limitations in available GABA(A)-based treatment of FXS, this group plans to investigate a novel selective GABA(A) agonist in a mouse model of FXS. This agent has the potential to relieve many symptoms of Fragile X without the unwanted side effects.

Read more

Tori Schaefer, PhD — Cincinnati Children’s Hospital

Tori Schaefer, PhD — Cincinnati Children’s Hospital

Development of a Novel GABA(A) a2,3 Agonist in Fragile X Syndrome with Craig Erickson, MD, Consultant FRAXA Awards: $21,000 in 2013 SUMMARY: Dr. Schaeffer used this 2013 grant from FRAXA Research Foundation to analyze an investigational new compound that targets the GABA-A receptor. This study has led to a clinical trial of the compound, led by Dr. Craig Erickson at Cincinnati Children’s Hospital. Of the many genes known to be regulated by FMRP, the gamma-aminobutyric acid receptor A (GABA(A)), is gaining attention as a potential target for the treatment of FXS. Mounting evidence suggests decreased expression and functioning of GABA(A) is involved in the pathophysiology of FXS. Non-selective GABA(A) agonism in animal models of FXS has been associated with normalization of morphological features, GABA(A) expression, and behavior. However, the clinical use of these agents in Fragile X is associated with unwanted side-effects, such as sedation, dulling of cognition, and occasional

Read more

GABAergic Inhibitory Function in Fragile X Syndrome

GABAergic Inhibitory Function in Fragile X Syndrome

With a $100,000 grant from FRAXA Research Foundation, Drs. Joshua Corbin and Molly Huntsman from the Children’s National Medical Center examined the role of a particular class of brain cells (inhibitory interneurons) that dampen excessive activity in the “emotional center of the brain” (the amydala). This inhibition is deficient in Fragile X, and so they are looked for ways to remedy this. This is particularly interesting to parents of children who are overly anxious and emotional. They worked with Dr. Walter Kaufmann, a clinician at Kennedy Krieger Institute in Maryland.

Read more

Neurobiology of Fragile X Syndrome: A Unifying Neuro-Endocrine Hypothesis

With a $74,000 grant from FRAXA Research Foundation, Dr. Abdeslem El Idrissi at CUNY explored the GABA receptor system in Fragile X mice and tested somatostatin and taurine as potential therapies for Fragile X; while somatostatin must be infused intravenously, taurine is available as a nutritional supplement.

Read more