When should innovation slow?
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Ophthalmology is a wonderful specialty because innovations come quickly.
As a group of practitioners, we welcome new technologies more quickly than other specialties. Rapid adoption of promising technology means that companies and investors support innovation in our field, and ultimately our patients are the biggest winners.
I sometimes wonder if there are times when we should deliberately slow down innovation. Gene therapy is one example. By inserting viruses into the body to rewrite the genetic code where a localized disease results from a defective protein, for example, we can “program” the body to produce the missing compound. In the case of macular degeneration, we can set up long-term delivery of anti-VEGF proteins that will obviate the need for regular injections. In the case of inherited retinal diseases, we can effectively cure what used to cause uniform blindness.
But should we be cautious when rewriting the genetic code? We know very well that inflammation results from introducing viruses that promote the altering of genes. In 2019, a group of ophthalmologists conducting trials on gene therapy identified a common finding: Dose-dependent intraocular inflammation occurred very commonly in treated eyes. Furthermore, other structural and morphologic changes of unknown significance were identified in treated tissues. Long-term steroid use seemed to be one possible solution, albeit with its usual side effects and risks. Other modes of inflammation control, such as biologics, may also work. Either way, we have to employ a long-term second treatment (anti-inflammatories) to manage the side effect of the first treatment (gene therapy).
What about other unintended consequences of gene therapy? Editing the wrong gene or affecting nearby genes that regulate cell growth can have catastrophic results. Last year, Bluebird Bio suspended two clinical trials for a gene therapy designed to treat sickle cell disease after two patients developed leukemia years after therapy. Gene therapy-induced cancer is not a new concept, and it does not appear to be dose dependent. Naturally, many different genes can contribute to a single biologic effect in the body, so changing one gene can have far-off implications that do not show up for many years.
Clearly, we must not let fear of the unknown hinder our efforts to develop gene therapies. Let’s face it, these diseases cause very clear human hardship and a demonstrable high cost. The nature of editing genes is going to require us to take some risk, even of severe consequences, if we are ever to see progress. As always, we should make decisions about innovation based on what best serves our patients. We have a lot of good work to do, but let’s do it as carefully as we can.
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