Choosing Gene Therapy: Reflections on Dosing, Before, During and After

An Interview With Seda Filenko

As one of the first families dosed with gene therapy, what were some of your thoughts, feelings, hopes, fears, anything you really considered as you made the decision to enroll in the trial?

  • The idea of gene therapy was circulating at the time of our diagnosis.  We had discussed the significant benefits with a few clinicians and research teams and the successful precedent set forth in use in SMA patients.  We were further encouraged by Généthon’s released video of gene therapy used in DMD canines and further gained an understanding of the importance and effects of different doses of the vectors.  We had enough information to feel that it was a safe and critical option for our son to move forward with gene therapy.  We were also always mindful of the fact that Duchenne is a race against time.  The earlier you can have access to gene therapy, the higher the efficacy.  We couldn’t afford to wait.  We also knew that gene therapy is mutation agnostic and would be the only potential treatment option available as our son has a unique mutation on his dystrophin gene. At that point for us, we knew that we had to get into one of the gene therapy trials as quickly and early as possible.

Once enrolled, what type of preparations were required before dosing?

  • We wanted to do everything possible to make sure our son would make it into the trial.  The preparations were immense.  We first switched from weekend dose to daily dose of steroids months ahead of enrollment in order to ensure that we qualify for all gene therapy protocols.  Once a commercial antibody test for AAV9 was available, we made sure to test as soon as possible, prior to enrollment, to make certain we knew which gene therapy trials we would qualify for.  We also knew that numerous non-sedation MRIs would be involved as part of the enrollment and were advised that if our son fails to complete MRIs correctly, we would not be able to be admitted into the trials.  We spent weeks training our son for MRIs.  We asked a hospital to have a practice MRI visit and spent hours each week mimicking a series of 90-minute MRI scans at home.  Of all of the MRIs, physical assessments, and biopsies involved, the most frightening part of everything to my son was the dozens of blood draws and IVs.  He cried every single time and it was heartbreaking.  And each time I questioned whether I was making the right choice.  He liked Super Mario at the time and I tried to turn the weeks of visits of the whole enrollment-to-dosing process into a leveled Mario game.  We drew a game board and moved the characters up through the levels as he completed each visit and task.  

What was the actual dosing experience like?

  • On our end, the actual dosing day was a relief. We had been preparing for so many months, and we were so happy that it was finally happening.  It was a long day with a lot of preparation and protocol at the hospital and clinic end, and we tried to keep our son distracted with device games, puzzles, and homework.  We had explained to our son that we would not be in the room while he receives the medicine but that he would have a device to play games on and watch movies.  We knew that he was in great hands with the amazing team of doctors, nurses, and research coordinators.  Dosing began nearly 12 hours after we had arrived at the clinic.  We stepped out of the hospital room for two hours and strolled around the hospital campus while the dosing occurred.  Once it was over, I stayed with our son in his room overnight, and the next day the hospital continued to monitor him.  We checked out and drove home 24 hours after his dosing.

What was your experience like days/weeks post-dosing? Did your son experience any side effects?

  • On the drive home after his dosing, our son began vomiting.  We assumed it was car sickness and did not think much of it.  In the following days, he was vomiting so much that he was unable to hold down water and we decided to go to the emergency room to get him fluids.  His general health and organ functions were completely normal, so after 3 days in the hospital, once we were able to control his nausea better, he was released to go home. The nausea remained and gradually dissipated over the next 3 months.

Did you notice any immediate changes with your son after dosing?

  • Because our son experienced so much nausea after dosing, we did not notice the typical heightening of activity that comes with the increased steroids in the first 60 days after dosing.  We did specifically notice that within 1 week after dosing, he was much sturdier when we picked him up.  He was severely nauseated and crying, but each time we picked him up, he felt so sturdy and together, and would even wrap his legs around us tightly, something that he had never done, and despite our frenzy in trying to hydrate and feed him, we were so happy to see these differences.