Dr. David Bloom investigated gene therapy for fragile X. The Bloom lab specializes in the development of gene therapy techniques, and they have succeeded in transferring the fragile X gene (fmr1) into the brains of live mice, using viral vectors. They studied ways to enhance this process, with the ultimate goal of gene therapy for people with fragile X.
The primary cause of fragile X syndrome is a genetic defect that results in the lack of a protein, FMRP. FMR1 knockout mice, which lack the ability to produce normal FMRP, show a number of central nervous system defects which may be similar to those present in the disease in humans.
Our goal is to develop a gene therapy approach to deliver a functional copy of the FMR1 gene into the brains of FMR1 knockout mice and determine if this will repair the observed defects in their central nervous system. Viruses that have been altered to make them safe (vectors) can be used as efficient delivery systems for gene therapy. We have been constructing two unique delivery systems to introduce the FMR1 gene into the brain. One system is a vector based on the Herpes Simplex Virus (HSV) and the second is based on Adeno Associated Virus (AAV), a harmless virus which often accompanies the common cold virus. Each of these two vectors possess different properties which will increase the likelihood of successfully delivering the FMR1 gene to as many brain cells as possible, as well as ultimately controlling how much FMRP is made. We have demonstrated that these vectors are capable of expressing FMR1. In collaboration with Dr. Bill Greenough’s laboratory at the University of Illinois, tests are underway to determine if vectored expression of FMRP can restore biochemical and behavioral functions that are lacking in the FMR1 knockout mice.
These experiments will allow us to determine if gene therapy is a possible therapeutic approach for treating fragile X syndrome. This study will also enable us to learn more about how the fragile X protein works, which may lead to the development of other types of therapies.