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Dispatches from ARVO 2015 Day 2

May 4, 2015

by Jennifer Phillips, Ph.D.

Day 2 is in the books, and, whether by virtue of my coincidental itinerary selection or of the magnificent foresight of the ARVO Annual Meeting organizers, today’s talks and posters were the ideal ‘next level’ to the material that was presented on Day 1. As I mentioned yesterday, the take home message from the first day of presentations was one of great hope and potential. The presentations I attended today, while no less committed to problem solving and advancement, were far more detailed about the mechanisms and limitations of emerging therapies. I heard many reports of unexpected outcomes, big changes in results when switching from one animal model to another, or from animal model to human, or from cell culture to a more complex system. In every case, though, the culminating message wasn’t one of defeat, but of resolve. Learning what doesn’t work is a huge part of ultimately successful science, although that fact often gets lost in the bacchanalian celebrations of experimental triumphs. It’s important to remember that we learn far more from trial and error than we can from instant success.

The big news that’s been buzzing through this meeting has to do with the most recent report on the LCA gene therapy trial. This trial was huge news a few years back (plug in the search term “LCA” to see my older posts on this study) because the early results of the Phase I trial were so promising, with many participants reporting (and measuring) vision improvements after receiving gene replacement therapy for this fairly severe form of RP. A subsequent report showed that, while the visual function improvements were sustained, the therapy did not change the rate of photoreceptor death in treated eyes. This most recent report showed that, indeed, after following participants for three years, the rate of degeneration continued unabated, and gains in visual function seen early on had declined by the end of the follow-up period. Also, somewhat surprisingly, younger participants with less advanced RP did not show better outcomes than older patients with worse vision at baseline.

While this is undoubtedly disappointing for LCA patients and the researchers who worked on this therapy, there is much to be learned from this first trial, and the drawing board is already full of modifications for the next go-round. Something to keep in mind is that this was a Phase I/II trial. The primary readouts were meant to address the safety of the treatment, which was a valuable gain in and of itself. Additional data obtained on treatment efficacy during the course of the trial was indescribably valuable for fine-tuning future attempts, and the researchers involved in developing this treatment now know how to use the existing animal models of this type of LCA to even greater advantage as well as to optimize the viral delivery system for future attempts.

This is how great science is done: Methodically, carefully, with optimism tempered by ruthless analysis of the data.  The Usher community is eagerly awaiting news on the UshStat trials using a viral delivery system to treat USH1B. This trial hasn’t been going on for long, so it’s far too soon to tell whether the treatment as it is currently designed will be effective and suitable for USH1B patients across the board. But, as a Phase I/II trial, just as in the case of the LCA trial, the primary goal is to determine the safety of the intervention, and that’s a crucial first step. Additionally, Dr. Richard Weleber of the Casey Eye Institute at OHSU presented some data today on the beautiful clinical tools that have been developed to monitor the visual function and retinal cell health of study participants. These tools, this trial, will be valuable to our community no matter what the outcome of the study may be.

Another big day is on tap for tomorrow, so stay tuned for the next update.

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