Genetic therapeutic strategies for Bardet-Biedl Syndrome

Genetic diseases are passed on from one generation to the next, and often have few treatment options or cures. Genetic diseases are caused by mutations in DNA, which in many cases leads to the inability to produce an important protein or enzyme. This can cause a vast variety of symptoms, depending on the gene that is affected by the mutation. An increasingly popular strategy to treat people with genetic disease is by a technique called gene therapy or gene replacement therapy, which uses various delivery methods to introduce a functional copy of a gene to a patient. A more recent technique to treat genetic disease is by using enzymes to directly change patient DNA to fix their disease-causing mutation.

Bardet-Biedl syndrome (BBS) is a rare genetic disease that causes many disease features in humans, including progressive blindness, male infertility, obesity, and intellectual disability. There are no effective treatments for BBS. My thesis research was aimed at providing a deeper understanding of why male patients with BBS are infertile, as well as testing the therapeutic value of gene therapy and gene correction for several of the disease features of BBS. I have shown that gene therapy to treat male infertility is effective in mice that have mutations in BBS related genes. However, if only a small amount of BBS protein is replaced in the eye or the brain of mice with mutations in a BBS gene, Bbs1, those mice still progressively lose eyesight and become obese. These results have shown us that we need to provide a very specific amount of replacement gene in order to treat blindness and obesity in patients with mutations in BBS1.