Ganaxolone for Fragile-X Syndrome

Fragile X syndrome (FXS), the most common cause of inherited mental impairment and the most common known genetic cause of autism. The impairment can range from learning disabilities to more severe cognitive or intellectual disabilities. Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and ethnic groups (source CDC). About 1 in 259 women carry fragile X and could pass it to their children. About 1 in 800 men carry fragile X; their daughters will also be carriers. About 20% of boys with fragile X will meet criteria for autism. Patients with FXS exhibit autism-like symptoms including cognitive impairment, anxiety and mood lability, attention deficit, and heightened stimuli. Thirty percent of people with FXS have seizures. People with fragile X are affected throughout their lives. Special education and symptomatic treatments are employed to lessen the burden of illness.

Fragile-X Pharmacology

Fragile X syndrome arises from a mutation of the fmr1 gene in the coding for the FMRP protein. Studies using the fmr1 knock-out mouse models confirm that there is a deficit in the production of GABAA receptors containing the neurosteroid binding site resulting in inhibition in the neocortex and down-regulation of the GABA-ergic enzymes and protein in cerebellum and neocortex. Consequences of the reduced GABAA receptor expression in FXS include heightened sensitivity to sensory stimuli, anxiety and seizures in up to 30% of patients.

Ganaxolone, with a high-affinity for the GABAA/ delta receptors, should increase signaling at existing receptors to normalize GABA-mediated inhibition to reduce anxiety, hyperactivity and learning disabilities associated with this inherited disorder.

To learn about our clinical trials, please click here.