One of the first lessons I learned in my career was that research study results often raise as many questions as they answer. Such is the case with new results from the gene therapy clinical trial for children and young adults with Leber congenital amaurosis (LCA, RPE65 mutations) at the Universities of Pennsylvania and Florida.
In the Proceedings of the National Academy of Sciences, the investigators report sustained vision improvement of three years, thus far, in the treated eyes of participants. However, they also note that retinal degeneration, the loss of photoreceptors, continued in the treated eyes at a rate that was similar to untreated eyes.
Before I elaborate on the questions these results raise, it is important to be clear on what we do know from the LCA gene therapy human studies underway.
First, the Pennsylvania-Florida team has treated 15 patients, providing vision improvements without any serious adverse events. Establishing safety is the primary goal of this Phase I/II study, and, thus far, the team has done that.
Second, patients in the other gene therapy clinical trials for LCA, including the study at the Children’s Hospital of Philadelphia (CHOP), have also experienced vision improvements without serious adverse events. CHOP has also reported good results in the treatment of some patients’ second eyes. More than 40 people have been treated in six LCA gene therapy clinical trials.
The most important and immediate question is: Are the other LCA (RPE65) gene therapy clinical trials also observing loss of photoreceptors in the treated eyes of their patients? Their teams haven’t formally reported information on rates of degeneration, but I’m currently investigating this to learn what they do know at this juncture. If they aren’t seeing loss of photoreceptors, then we need to figure out why there are differences in retinal degeneration in treated eyes among the different studies.
If investigators at the other trials are observing continued retinal degeneration, it may mean that we need a more advanced form of gene therapy, to ensure that all of a patient’s photoreceptors are treated. Such a therapy might do a better job of slowing or stopping degeneration and preserving vision over a longer period of time.
Or, we may have to combine gene therapy with a drug or supplement that can stave off degeneration. These recent study results may also underscore the benefit of treating a patient early, before the degenerative process has time to gain momentum and becomes more difficult to stop.
I am very interested to see what will be observed in the early-stage gene therapy clinical trials underway for other retinal diseases. Thus far, we only have preliminary safety reports, so we’ll need to wait and see how these therapies impact both vision and retinal degeneration.
One of the big challenges in fighting blindness is the diversity of retinal degenerative diseases, and the likelihood that one approach to gene therapy will not work for all conditions. But the good news is that the retinal research community isn’t putting all of its eggs in one gene therapy basket.
As current gene therapy clinical trials move forward, and more are launched in the next two to three years, we’re going to learn a lot more about which approaches work well and which need refinement. I look forward to reporting additional information on these gene therapy studies as I get it.