Justin Cohen: Living with FSHD, and efforting to find a cure

Justin Cohen (@TheChair1130) is a remarkable young researcher, living with FSHD, and efforting to find a cure for the disease. The Carrino Foundation is proud to make his work possible. Here is Justin’s story, in his own words:

When I was born, it was not immediately apparent that there was anything different about me. Due to the insidious onset of FSHD, my major muscle weakness was not immediately obvious. As a young child, my parents noticed that I would always respond to my father’s deep voice, but couldn’t hear when my mother was talking to me. This early hearing loss was the neurological sign of what would later be a life altering muscle disease. I wasn’t officially given hearing aids until four years old, at which point the doctor stated that I would never recover from the lack of exposure to language during those critical years for early language and cognitive development. As I recently accepted my doctorate degree, I am happy to say that he was very wrong.

It was shortly afterwards that I was formally diagnosed with FSHD. Luckily for my family, my path to diagnosis was not as arduous as most patients. Both my parents are in the medical field, and I quickly received a clinical diagnosis from Dr. Spiro, one of the top muscle disease specialists, who luckily lived only an hour and a half away. A blood sample was sent to the Netherlands to genetically confirm the results, as there were no existing testing sites in the United States at the time. This test also confirmed that my diagnoses was a result of a spontaneous genetic mutation; both my parents and siblings tested negative.

My childhood development was otherwise normal throughout most of elementary school. I was never the strongest kid in my age group but my muscles were growing. Things changed once I turned 11. It started as a limp in my left leg that required me to wear a foot brace. By the time I was 12, I was starting to use crutches. At first, I mainly used the crutches in school, helping to speed up navigating the
long hallways of middle school. At home I tended to use whatever I could to be independent from a device, including use of walls, countertops, grabbing my knees for support, or even crawling; much to my parents’ chagrin. By high school, I could no longer convince myself that I was just like my peers. Due to the school’s size, I had no choice but to use a power wheelchair in order to make it to classes on time. I required a new bus to school with a wheelchair lift, preventing me from riding the bus with my friends. My homeroom was changed nearly every year in order to be closer to my first class. Gym class was no longer with my friends, instead it was a much smaller class focused on those with disabilities. I had to leave every class several minutes early to navigate the halls before thousands of students poured from the classrooms, causing me to miss valuable education time each day.

In ninth grade my scoliosis became so severe that I required a spinal fusion surgery. This had profound effects on my mobility, changing my life forever. Post-surgery, my body could no longer compensate for my broken ambulation the way it used to. My balance and endurance on crutches was significantly affected, and I was completely wheelchair bound shortly after.

Around this time was when I began attending physical therapy. There are some in the field who recommend physical therapy as a way to help maintain muscle strength/ slow the decline. However, my personal experience has taught me that it is vital that you do not over exert yourself. My time in physical therapy coincided with the dramatic and rapid decline in my muscle mass and strength throughout my life at the time. The fact that this occurred in the muscles that we focused on the most in physical therapy is too much of a parallel to be a coincidence. I have noticed that the research on exercise tends to be on those that developed FSHD much later on in life, leading me to consider that exercise may affect patients differently, depending on age of onset.

After this, my muscular atrophy became subtler visually, but the physical effects were just as consequential. Raising my arms on their own became a challenge and then impossible without using the other arm for support. Getting out of bed changed from a ten second mindless action, to a 20-minute endeavor. Transferring in and out of my chair became a complex physics equation with risky
consequences. Still, to the best of my ability, I tried to adapt.

When I left for college in fall of 2008, my initial plan was to go to medical school. However, I quickly realized that I was unwilling to wait for the day I would no longer be able to adapt to my quickly deteriorating body. I resolved to take matters into my own hands by getting my PhD with the goal of pursuing FSHD research. Thanks to a fellowship from the Chris Carrino Foundation for FSHD, I am now able to realize that dream as a Postdoctoral Researcher in the Lek laboratory at Yale School of Medicine. This path was not as simple as it may sound. As an FSHD patient, there are many physical tasks I am unable to perform, and laboratory work requires precise and complex maneuvers or dexterity and coordination. I was fortunate that during my time earning my PhD at Drexel University, I was provided a handicapped accommodation from their disabilities/equal opportunity office in the form of a research
assistant that could act as my “hands” in the laboratory. I directed the assistant step-by-step at their side for the physical experimental manipulations, which allowed me to perform my thesis work. Acquiring this same accommodation for my postdoctoral research proved to be much more difficult. However, with enough perseverance, I was provided with this assistance from an MDA grant, which has
allowed me to actualize my dream of researching FSHD.

The research at Yale is particularly meaningful to me as an FSHD patient, as it directly involves identifying drugs that can be used as potential treatments. As many of us with FSHD know, there is a wide variability in the degree that the disease affects us. This suggests that there can be some aspect of our biology which makes us more “resistant” to FSHD progression. The Lek lab took advantage of this by using a gene editing tool called CRISPR to randomly induce mutations that inactivate genes in a muscle cell line. They then increased expression of DUX4, the toxic protein associated with FSHD, and identified which mutations prevented cell death. I am now evaluating pathways associated with those mutations and testing drugs that inhibit those pathways to see if we can mimic the effect of inactivating the genes. Most importantly, I am emphasizing drugs that are already FDA-approved, meaning drugs that are already used in patients for other diseases. Since the drugs have already been evaluated for safety, very little time needs to be spent during clinical trials assessing the harshness of side effects. This will significantly reduce the wait before a treatment becomes available for patients.

So what’s next? We plan to take any drugs that show promise in our patient cell culture experiments and test them with our collaborators in mouse models of FSHD. These models have improved dramatically over the years and we now have greater control over the degree of muscle weakness present, making them more like that experienced in patients. Overall, I am very optimistic that FSHD research is moving forward on a promising path. Not only has there been an exponential increase in our knowledge of FSHD within the last 10 years, but the scientific advances have allowed our research tools to become more sophisticated as well. Initially, I would expect to see treatments that can halt or reverse disease progression, and as gene editing technology improves, a complete cure. With the help of the Chris Carrino Foundation for FSHD and my colleagues in the Lek lab and beyond, I for one, cannot wait to be a part of this journey.