Changes

It's fall here in New England, and the leaves are just beginning to change. It's still hot and sunny outside most afternoons, but the evenings are turning cool, and the mornings are misty and dark and there is the temptation to stay in our cozy beds just a little longer. School has begun and fall has arrived. These early stages of transition seem to echo the experiences our family has had over the past couple of months. Things are still pretty much the same, but changes are coming.

It was fall when Griffin was diagnosed five years ago, just after Thanksgiving in 2013. My family was still reeling from the loss of my cousin, Jenn, who had just passed away from cancer at the way-too-young age of 38. I will not tell that story here, since it isn't mine to tell, but the two events are tied together in my mind. I can't think of one without thinking of the other. I brought baby Ronan and 4-year-old Griffin with me to her celebration of life. This picture of Griffin was taken there. At the time, we were in the midst of doctor appointments and tests to find out why he still couldn't jump with both feet off the ground, alternate his feet on stairs or run. I remember watching him walk around the field that day and noticing the little waddle he had. I remember that he went into the bouncy house and was bounced around by the other kids jumping and couldn't stand up. In a few weeks, he would have an MRI and bloodwork. The MRI would reveal nothing out of the ordinary. The bloodwork would reveal everything. I expected that whatever was causing his mild symptoms wouldn't be too serious. There had been some small complications during his birth, perhaps he had a very mild form of Cerebral Palsy. It never even occurred to me it could be something progressive, and of course it had never crossed my mind that it could be fatal. Deep down, though, I think I knew. I remember that I had a feeling of foreboding that fall, and had assumed it was just part of the shock and sadness I was feeling about Jenn. It was a nagging feeling though, an unsettling one. After his MRI, I remember feeling strangely emotional, some part of me aware that we were about to get bad news. His MRI was in the morning, and that afternoon, the developmental pediatrician called to say that his MRI was normal, but that his bloodwork indicated some form of muscular dystrophy. "Don't google it" was her advice. I googled it, the world crashing down around me piece by piece with each word I read.

In the spring of 2016 (spring, the opposite of fall, a time for new beginnings, new hope and new life) Griffin began a clinical trial. The drug in the trial was a myostatin inhibitor. Myostatin is the enzyme that stops muscles from growing indefinitely (without it, we would all be like The Hulk). By inhibiting it and taking the brake off of muscle regeneration, it was hoped that the boys in the trial would be able to regenerate muscle more quickly and as a result gain strength and slow the progression of the muscular dystrophy. The trial was designed so that 1/3 of participants would receive an escalating dose of the trial drug for two years, 1/3 would receive placebo the first year and drug the second, and 1/3 would receive drug the first year, and placebo the second. For the first few months, we weren't so sure anything was happening. But at about month 3, we noticed little things. We went on a walk down a trail near our house against my better judgement. I wasn't sure Griff could make it the whole way, and I didn't relish the idea of having to carry him back if he couldn't do it. But he insisted, and I actually had to hustle a little to keep up with him. It was the first time I could remember having to try to keep up with him. Hmmm. By month 4, we were sure. He began alternating his feet going up stairs (rather than taking the steps one at a time, like a toddler does) and his run started to look almost like the run of a healthy child, just a bit slower. He had more energy, he seemed to move through the world with more ease. During the second year of the trial, he slowly settled back into his former ways, and in the last few months he was slowing down noticeably. He was having more difficulty with stairs, we didn't see him running much anymore. So we assumed he was on placebo for the second half of the trial, and hoped against hope that when he started the extension study (the extended part of the trial in which all participants are on the drug with no chance of placebo), we would see a little of a rebound back to the gains we saw during the first year. 

About four months into the extension study, we noticed little things again. A little more energy, a little more spring in his step. Some of the difficulty he was having with stairs seemed to ease up. He didn't have a dramatic return to where he was at the end of the first year as we hoped, but it seemed to be moving in the right direction again. We went to his fourth monthly trial visit to Pittsburgh in August feeling optimistic, and Griffin breezed through "the pokes" without a single complaint. I think it was our easiest visit. I hoped that this dose would be the one that reminded his body what it could do on the drug.

A week after his fourth open label dose, and mere days after I watched him go up the stairs to our house with less effort than usual, we found out that Pfizer, the company sponsoring the clinical trial, had decided to end the trial effective immediately. Ironically, they had analyzed the data and it turned out that there was no significant difference in the time it took the placebo group and the drug treated group to ascend four stairs. This was their primary endpoint. The data did not support continuing the trial, as it showed no difference from placebo on the timed four stair climb. I will suggest here that timed tests may not be the best trial design for drugs for Duchenne. Our trial coordinator noted that while the time to go up the stairs may not have changed, the way the boys approached the stairs did (using the railing less, alternating feet, not pushing a hand off of their legs). But the only thing that counted toward the end point was time. In any case, the results were not overwhelmingly positive, and Pfizer is a business after all. Why continue to invest in a drug that will never make it through the FDA approval process? 

I knew from talking to other parents that some boys didn't seem to be responding much to the drug, and either stayed the same or declined a little during both years of the trial. But I also knew from talking to other parents that many boys improved, some significantly. I also knew that my own son had most certainly shown improvement during the first year. However, Griffin and the other boys who improved were apparent anomalies. Even though I knew this could happen, it came as a total shock. We had been talking about the possibility of taking him out of the Pfizer trial to try and get him into a different trial that could potentially address the underlying issue of lack of dystrophin, rather than just treating the symptoms. There is a "wash out" period of 3-6 months for boys who want to change trials, so we were trying to decide when the right time might be start the wash out and be ready when the trial we had our eye on started recruiting. A gamble, since we actually have no idea when it will start recruiting, and there was a chance he could decline during the wash out to the point where he wouldn't qualify for the next trial, AND we heard there were wait lists hundreds of boys long for some of these trials. This is a good thing, it means these newer drug trials are looking good and everyone is hopeful this will finally bring a real, life-changing treatment that would turn Duchenne into a manageable chronic condition, rather than a terminal disorder. In any case, the sudden cessation of the trial made the decision about when to start "washing out" for us.

The funny thing is, despite the fact that we were already considering taking him off at some point, the news was devastating. It was reminiscent of when he was first diagnosed, which is perhaps why I am finding myself beginning this blog post with memories. Fall is a time of change, but also a time of reflection and remembrance.

We had no idea when we went for his August trial visit that it would be our last. The routine of going to Pittsburgh every month gave me a certain level of comfort. I knew that we were doing absolutely everything we possibly could for him, and this was enough for me to feel at peace with whatever was coming, and hopeful that it wouldn't be as bad as I imagined. Having the psychological safety net the trial visits were providing suddenly torn away, I found that, in fact, I was still in free fall and always had been, but the net had given me a sense of security. Now, I feel a little like I am aware again of the bottomless pit below me, and I am grasping at thin air, hoping to find something to grab onto.

In addition to the heartbreak about the trial cancelation, Griffin has been recovering from an ileotibial band injury over the summer, followed quickly by a foot injury on the second day of school. This means he has been using his wheelchair more. Even though he isn't using the wheelchair more because he is weaker, seeing him in it more and having to lug it around everywhere feels like an unwelcome taste of changes to come. 

I have written before about the silver linings of having this in our lives, and none of that has gone away. We appreciate little things more. We say "yes" to more experiences and have more fun than we would have. We have had the gift of experiencing what it is like to have infinitely supportive family and friends. When he was first diagnosed, I spent a lot of time worrying about what life would be like for Griffin now, at almost 10 years old. Would he be in a wheelchair full time? Would he have any cardiac or pulmonary symptoms? Would we have the means to make the adjustments necessary to make school, our house, the world, accessible for him? Would he have friends? Would he be bullied? Would he be unhappy? It turns out, none of those fears have been realized, and I wasted all that time worrying for no reason. I still have those same fears about the future, but I also know now that none of it is insurmountable. We can handle it, whatever "it" may be. Last week, he went on a hike with his school. It was a 4-mile hike and he walked a mile and a half of it on his own. Brian piggy-backed him for the rest of it. I have just the right partner in parenting this gift of a child. Brian would do anything for him. At this point, Griffin weighs half of what Brian weighs, and yet he carried him through the woods with a smile on his face and without complaint.

Worrying doesn't change anything, it won't make any difference in his future if I spend all my time worrying versus just trying to make the most of each day. I try to remember that now, during this time of transition when my fears about the future begin to overtake me. Treatments and even potential cures for Duchenne are happening at a rapid pace, and the outlook seems to change (in roller coaster fashion) almost daily. One trial gets canceled while another reports astoundingly positive preliminary results. Things change for Griffin, but he always adjusts quickly and is impressively resilient. By now, his summer injuries have healed, and he is back to his normal speed and gait. Naturally, I worried (unnecessarily again, it seems) that the summer injuries would be the beginning of the end of walking for him. They weren't, and he is his usual happy, optimistic self. He does worry too, and he has wondered out loud if the end of the trial will mean he will get worse. But he doesn't let any of it get him down for long. He is here to live life to the fullest no matter what, and shows no sign of letting anything get in his way. The truth is, we have no idea what is next, and Griffin has surprised me too many times for me to think that I can make any assumptions.