With a $90,000 grant from the FRAXA Research Foundation from 2013-2014, Dr. Andres Ozaita led a team to test rimonabant’s ability to blockade the CB1 receptor. Blocking CB1 has shown potential to reverse most symptoms of disease in mice bred to mimic Fragile X syndrome.
Susana Mato Santos, PhD
This team in Spain recently published a high-profile paper demonstrating that blockade of CB1, a major receptor for an unusual class of neurotransmitters called endocannabinoids, could reverse most features of Fragile X in the knockout mouse model. They used a drug called rimonabant, which had been marketed in Europe as a weight-loss treatment. However, rimonabant was withdrawn because of serious psychiatric side effects, including depression and suicidal ideation, so it is far from ideal as a potential treatment for Fragile X.
In this project, the investigators will study the effects of low doses of rimonabant, which may be able to treat Fragile X without unacceptable side effects. They will also examine the effects of other CB1 antagonists, with different mechanisms of action, which may be more useful in treating Fragile X.
This approach is based on modulating the cerebral endocannabinoid system. Using genetically modified mice that lacked FMRP protein, this team showed that blocking CB1 cannabinoid receptors with rimonabant can correct cognitive alterations, sensitivity to pain and epileptic crises.
Nature Medicine, 2013: Targeting the endocannabinoid system in the treatment of Fragile X syndrome