And at Last I See the Light, because a Virus Implanted into my Eye is Fixing it

If you’re a Disney princess with long hair flowing down the side of a tower, then seeing the light means sharing a duet with the dashing young man next to you. For Dr. Katherine High it means a breakthrough in gene therapy and for thousands of patients with LCA it means hope.

Following an announcement by Spark Therapeutics, there is a new light to be seen for patients with an inherited retinal disease. This is a literal statement, as the company’s new gene therapy helps restore vision to patients with Leber Congenital Amaurosis (LCA). LCA causes night blindness and peripheral degeneration and can eventually lead to blindness. LCA is one of the leading causes of blindness among children. It, as well as other blindness inducing mutations, affect an estimated 3,500 people in the U.S. and Europe. Data was collected by having subjects navigate through an obstacle course at varying light levels. Spark Therapeutics, co-founded by Dr. High, revealed that subjects who underwent their therapy experienced a significant improvement in their low-light vision, shown by their increased ability to navigate themselves.

How does this gene therapy work? Spark Therapeutics reveals that they implanted a virus carrying RPE65, a gene that helps maintain the health of retinal photoreceptors. By incorporating RPE65 into a relatively inactive form of the virus, it can in turn be incorporated into the genome of targeted cells. According to Lief Fenno et al of Stanford University, this viral vector therapy has “the dual advantages of fast/versatile implementation and high infectivity/copy number for robust expression levels.” It is a powerful tool for gene manipulation commonly used in optogenetics.

Optogenetics combines gene manipulation with light stimulation. By inserting certain light sensitive proteins, namely opsins, scientists can use a light stimulus to manipulate that cells behavior. Optogeneticists commonly use the same viral implantation method of gene manipulation as used by Dr. High and Spark Therapeutics. The same tool is used by Dr. Steidel of Loyola University Chicago. Dr. Steidel studies reward pathways of the brain. By using optogenetics he is able to determine the roles of different proteins in the dopamine system.

In both cases viral expression systems provide a unique advantage to researchers. The manipulation of genes and the expression of proteins is a powerful and promising tool. Already Spark Therapeutics’ application is closing in on becoming one of the first gene therapies approved in the U.S. While the application is not quite ready for market yet, this breakthrough in gene therapy shows great promise for the future of medicine.

"Eye Treatment Closes In on Being First Gene Therapy Approved in U.S." New York Times. N.p., 5th Oct. 2015. Web. 15th Oct. 2015 

http://www.nytimes.com/2015/10/05/science/eye-treatment-closes-in-on-being-first-gene-therapy-approved-in-us.html?action=click&contentCollection=science&region=stream&module=stream_unit&version=latest&contentPlacement=48&pgtype=sectionfront

Fenno, L., Yizhar, O., & Deisseroth, K. (2011).The Development and Application of Optogenetics. Annual Review of Neuroscience, 34: 389-412. Retrieved from 

https://luc.app.box.com/neuroscienceseminar/1/4284607235/35367156127/1