On The Road to Personalized Therapies for Blindness: New Study Reveals Why Genetic Testing is Vital

January 31st, 2017 by FFB Canada

Photo: Ruanne (left) with her familyEvery day, my research is focused on developing an effective treatment for the blinding eye disease retinitis pigmentosa (RP). Recently, we made an alarming discovery: the SAME drug makes some genetic forms of RP better and others worse. This means that knowing the genetic cause of RP is essential.

Our FFB-funded, award-winning research project is hot off the press in the Journal of Neuroscience. After I was diagnosed with RP in 2010, I contacted FFB-funded scientists, Dr. Orson Moritz to express my desire to help advance RP research. With Dr. Moritz’s mentorship, our team investigated the role of valproic acid (VPA) and other related drugs in four different genetic models of RP. Using tadpoles with human RP mutations in their DNA, we found that the drugs had different effects on the tadpole’s photoreceptors depending on their type of mutation: for one type of mutation, the drugs slowed down the retinal degeneration. But, for the three other mutations, the drugs made the condition worse.

Imagine you are trying to put out a fire. You must determine if it’s a wood or a grease fire. Using water to extinguish a campfire works perfectly well, but is highly dangerous to put out a grease fire. The same logic applies to treating RP: in order to stop or slow down the degeneration, it’s important to know the genetic cause.

The tricky part of this project was figuring out how VPA was doing its job to help one form of RP but worsen other types. This is because VPA has a handful of different pharmacological activities. It took many months to figure out which one of these activities affects retinal degeneration. In the end, we found that VPA had an activity that regulated the epigenome.

What is an epigenome? Think of an orchestral score as the genome. The epigenome, or the “above” genome, is the music that is played by the musicians. The musical score is the same, but the music can be played in many ways by the flutist or the oboist. Similarly, the genome can be “played” differently by different regulators, depending on the genetic and/or environmental condition. Interestingly, our research suggests that proper regulation of “music playing” is important for retinal health.

How does our work advance RP research? We are starting to understand that genetics plays a heavy role in developing an effective therapy of RP. Currently there are over 60 genes known to cause RP and genetic testing is not standard practice. Until recently, there was no reason to do so. In the future, I believe that genetic testing in people living with RP will be standard practice and this will be vital in advancing personalized RP therapies.  Our results strongly suggest that future clinical trials for RP therapies should always collect genotype information on patient participants, in case some genotypes respond differently. We are also looking forward to the results of the recent Phase II clinical trial testing VPA as a potential treatment for retinitis pigmentosa.

Lastly, I express sincere gratitude to Dr. Moritz for his amazing mentorship throughout my PhD since 2012. Dr. Moritz never made me feel that my visual impairment was holding me back. He treated me as an equal member of his research team and provided a safe, team-building learning environment. I have been in medical science research for over 12 years and Dr. Moritz is a truly inspiring scientist and leader with an authentic kindness that is rare in the competitive research environment.

Thank you to all of the FFB donors. Without your financial support, our research would not have been possible. Your help brings us one step closer to finding a therapy for RP and helps to keep my hopes up about never fully losing my sight.

About the study:

Vent-Schmidt, Ruanne et al. 2016. Opposing effects of valproic acid treatment mediated by histone deacetylase inhibitor activity in four transgenic X. laevis models of retinitis pigmentosa. The Journal of Neuroscience doi.org/10.1523/JNEUROSCI.1647-16.2016

By: Ruanne Lai, PhD Candidate

Ruanne’s research project won best poster award at the 2014 International Symposium on Retinal Degeneration in Pacific Grove, California. Ruanne also won best oral presentation for her research at the 2013 Research Day in the Department of Ophthalmology & Visual Sciences at UBC in Vancouver, BC. She is an invited panel speaker at the FFB Vision Quest Vancouver Speaker Series on March 1st, 2017.