Stanford Scientists Awarded $90K to Screen Therapy Combinations

The FRAXA Research Foundation has awarded a $90,000 research grant to Stanford University scientists to evaluate the effects of potential therapy combinations in fragile X syndrome.

The project will be led by researchers Philippe Jacques Mourrain, PhD, Gordon Wang, PhD, and Rochelle Coulson, PhD.

Fragile X syndrome is a genetic disorder characterized by developmental problems that include cognitive impairment, learning disabilities, and hyperactivity. It is caused by defects in the FMR1 gene, resulting in abnormal brain development.

Lack of FMRP — the protein produced from FMR1 that is necessary for normal brain development — affects the migration of neurons (nerve cells) to form brain circuits, causing these developmental problems.

Although there is still no therapy to target all the deficits observed in the brain of patients with fragile X syndrome, new therapeutic strategies have the potential to improve their lives.

Thus, the main goal of the researchers is to evaluate the additive effects of combinatorial pharmacological therapies and their ability to correct a wide range of brain deficits.

The scientists will use a combination of imaging and molecular techniques in both human cell culture models and mice brains.

“The use of human [fragile X syndrome] cells will improve the clinical significance of our study, allowing us to quickly test a large number of drug combinations in the context of actual patient conditions,” the scientists wrote.

They intend to create a map of the changes that happen in the brain of both humans and mice that are caused by the loss of the FMRP protein and in response to pharmacological treatment. The team expects that this project will improve the translation between the mouse model of the disease and the abnormalities observed in patients’ brains.

The researchers will also assess potential treatments for the development of tolerance — or diminished response to a treatment as the patient’s body adapts to it after repeated use — a critical issue in long-term therapies. They will also evaluate the effects of therapy combinations in patients’ brains to identify improvements in cellular pathways that underlie the deficits found in the brain.

“This analysis opens the possibility that drugs are not tied to a single disease, but to specific deficits, and that a combinatorial approach can be devised to target the array of deficits observed for any neurological disease,” the scientists wrote.