Keeping Hope In The Fight Against Neutralizing Antibodies

As difficult as it was to get the news that Fritz was not going to be amenable to the current gene therapy trials, I ultimately had some degree of peace, because I had knowledge. Knowing what we know about Fritz’s Neutralizing Antibodies levels not only helped us navigate our hope, it has given us a better idea of some important work that still needs to be done to save our son, and others.

It was nearly 3 years ago. After grieving a Duchenne diagnosis of our son, we yet again found ourselves grieving. Grieving an unexpected answer to what we thought was an opportunity to save his life. My 3 boys and I headed out to enjoy a beautiful day with a hike through the Arizona desert. As I was loading up the car to head home my phone rang. Recognizing the area code was from his neurologist, I anxiously answered.

“We have the results of the bloodwork we ran at your last visit,” a quiet voice shared on the phone.

“Both shockingly, and unfortunately your son’s AAV Neutralizing Antibody levels came back too high, making him ineligible for our Gene Therapy Trial.”

“Ok,” I said, my voice starting to quiver. “So that’s it, is there anything we can do? Is there anything being done to solve this problem?”

“Unfortunately right now, there is nothing you can do. We can check his levels again in 6 months, see if they’ve changed. We are aware this issue exists, and there is some early research being done to figure out how to solve this problem, but there is nothing that we can do right now.”

Just as the tears, anxiety, panic attacks came with the diagnosis, I found it all, every difficult, ugly emotion, yet again ever present. As a mom, all you want is what’s best for your kids. And I couldn’t help but hurt deeply and cry hard, when I learned that a therapy I thought was going to save my boy, was no longer any option.

I looked back at an old journal I wrote during this time and found these words:

“I feel that the idea of being hopeful can often lead one to a better sense of optimism. And I like optimism, I think it’s good and healthy. Hope gives reason to keep seeking after. Hope paired with determination leads to progress and to change. However, I think one has to be cautious when being hopeful; especially in the world of Duchenne. I find myself hoping every day that something will be done and that a cure will be found for my wide-eyed, curly-haired little boy. But I fear, when my hope exceeds the reality of our circumstance, feelings of disappointment soon follow. I want to be hopeful. I want life to be different for Fritz. But I worry that if I spend too much time hoping, I will ultimately spend so much of my time hurting. How do I hope, when there is no guarantee what I hope for will happen. How do I hope in a realistic way, maintaining a sense of optimism, while not losing sight of the fact that Duchenne only gets worse with time? I’m finding that with Duchenne there can be so much hope, but also, so much reality. I’m often confused about what ride to ride. How do I balance hope and reality? I want to be hopeful, but I fear the disappointment that can follow. Wishful thinking has led to high levels of anxiety and heartache. I hoped, when all this began, that it was something as simple as a food allergy, but there we were 6 months later with a diagnosis of Duchenne. I hoped this gene therapy clinical trial was it, that he was going to be a part of some major progress, but here we are with a phone call informing us otherwise. Hurt. Confused. Almost wishing we hadn’t hoped. Is it possible to hope in a way that leads to progress and not pain?”

Since this entry, I’m continually learning to view closed doors as opportunities to think differently,  invitations to learn more, nudges in a different direction. Closed doors are answers, even if they aren’t the answers we were initially looking for. This doesn’t mean that these closed doors don’t feel like they slammed your finger in them when they flew shut, (You better believe I yelled a few choice words after I hung up the phone with the nurse that day).

Weirdly though,  as much as this news prompted me to cry and grieve, almost like I did the day he was diagnosed, I soon found myself with a piece of information that few people had. I soon felt like I could hope again because I knew where it was safe to place my hope.

As difficult as it was to get the news that Fritz was not going to be amenable to the current gene therapy trials, I ultimately had some degree of peace, because I had knowledge. Knowing what we know about Fritz’s Neutralizing Antibodies levels not only helped us navigate our hope, it has given us a better idea of some important work that still needs to be done to save our son, and others.

And I think that might be a part of the answer to the question I posed to myself years ago in my journal.

Is it possible to hope in a way that leads to progress and not pain in the world of Duchenne? I think so, but a key piece to my hope has been knowledge and information. Information has not only helped set realistic expectations for my hope, information, and knowledge have pointed me to other work that still needs to be done. Hope that leads to progress requires work and action. And efficient and effective action can only be done when people have access to information.

In our journey of raising a son with Duchenne, I do believe hanging on to hope is important, because oftentimes, it can feel like all we have.  However, I think it is also fair to expect and have access to information that lets us know how to hope, and/or where to place our hope. We continue more forward, cautiously hopeful, knowing what work still needs to be done to not just save our son, but many who may unknowingly find themselves in a similar place. Like I said, I find myself weirdly grateful to know Fritz has AAV neutralizing antibodies, because I think if we didn’t, we may have spent the last several years just sitting around hoping for something that in the end wouldn’t work for our son. Instead, we have answers that have allowed us to focus on finding more answers; for instance, how do we overcome this issue of preexisting AAV antibodies?!

In our experience thus far, Hoping with little information is nothing more than wishful thinking and where we yet again find ourselves confused and hurting. Hoping with answers, however,  has allowed us to make decisions that ultimately lead to progress. And progress will be what leads us to an open door, to a cure, not just for our son, but many others living with rare disease.

Basic Info one needs to know about AAV Neutralizing Antibodies (NAb’s):

-Antibodies are the body’s defense mechanism against foreign pathogens (viruses). AAV is a type virus used to deliver therapeutics

-Certain levels of NAb’s can cause the body to attack AAV virus instead of accepting it as a helpful therapeutic.

-Whether micro-dystrophin or CRISPR, Individuals can have pre-existing NAb’s to the AAV virus as a function of everyday life.

-There are different versions of AAV (called serotypes), and it is unclear what/ if there is any correlation between having antibodies from one version of AAV to another.

-It’s speculated that antibody levels can fluctuate over extended periods of time.

-It is unknown exactly how many patients have higher levels of NAb’s preventing them from receiving any AAV mediated therapies.

-There is research being done to figure out how to make those with antibodies amenable to therapies using AAV; however, there is still more work and funding needed to be done to make this a viable option for patients and families who find themselves with certain antibody levels.

-CRD has partnered with the University of Massachusetts Medical School to provide Cure Rare Disease families the opportunity to test and gain knowledge about NAb’s in efforts to help themself or their loved one make the best decision for therapeutic options.

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