The Morgan Hoffmann Foundation believes in the power of research. Along with celebrating individuals who have shown great strength through their diagnosis, the Foundation also believes that recognition must be given to those who are making great strides in the community. The 2019 MHF Research Grant of $10,000 was awarded to Elisabeth Kilroy, a PhD candidate in Dr. Clarissa Henry’s graduate lab at the University of Maine, for her work related to zebrafish and muscular dystrophy.
I was six when I realized that my father was different. As I was learning to play sports, he could explain how to do certain movements but could not physically show me how to do them. This made me curious about why his muscles did not work like mine. When I was 11, I witnessed the inability of his muscles to catch him from a fall which left him paralyzed and left me unable to understand why he would never walk again. I remember being angry at the doctor for telling my brothers and I that there was no way that our father would take another step. This was the moment I fell in love with muscles.
Five years later, muscular dystrophy stole my brother’s dream of competing in the Winter Olympics as a freestyle skier. When I asked my father why, he explained to me that muscular dystrophy results in the loss of muscle mass due to repeated cycles of muscle fiber degeneration and regeneration that then culminate into a progressive muscle weakness. I could see this process occurring in Keegan. One year I watched him perform backflips off a ski jump and a year later I watched him spend three minutes tying one shoe. During this time, I was recovering from my second of three knee surgeries. I lost almost 70% of my muscle mass and I forgot how to lift my leg. This fascinated me. I had to retrain my muscle to contract, and I had to perform repetition after repetition to get my muscles to grow. I asked my physical therapist an endless of amount of questions about my own recovery, and these questions eventually turned into questions about muscular dystrophy; why can my muscles regrow but Keegan’s muscles could not?
As I began my applications for college, I knew one thing: I would study exercise science and learn everything I could about skeletal muscle and human movement. For every research paper I was assigned, I chose a muscle disease as my topic. From these assignments, I learned that there are lots of different types of muscular dystrophy caused by mutations in different genes that help maintain muscle structure and function. I asked Keegan if the doctors knew what type of muscular dystrophy he had or what gene was causing his symptoms. He said the doctors did not and then left it at that.
I was not going to let doctors give up on Keegan so quickly. A genetic diagnosis means that the moment a potential cure is identified, he can enroll in the treatment plan. Without that genetic diagnosis he would never know about potential therapies. I decided to dedicate my life to understanding muscular dystrophy and finding a cure for every single type. I am now a PhD Candidate in the Graduate School of Biomedical Science and Engineering at University of Maine. UMaine was the only school that believed in me and was excited to support my dreams of curing muscular dystrophy.
My research at UMaine stems from a phone call with Keegan. As he became more and more involved with golf, he wanted to protect the strength he still had. As a certified personal trainer and exercise scientist, I had never learned about exercise programs for individuals with muscular dystrophy. I told Keegan I would do some research and put together a plan. Unfortunately, I could not put a plan together. After reading through the literature I learned about a long-standing consensus that strength training is detrimental to dystrophic muscle. Since individuals with muscular dystrophy are missing a critical protein needed to build and maintain healthy muscle, their muscles are believed to be more susceptible to damage during muscle contractions, and strength training may speed the progression of the disease. Therefore, individuals with muscular dystrophy are advised to refrain from physical activity in order to protect their muscles from further damage. I was not convinced. I knew that inactivity caused muscle wasting in healthy individuals and I knew that strength training was the primary stimulus for improving muscle mass as well as muscle strength and function. With my advisor away at a weeklong conference, I decided to pursue my biggest question: what comes first –muscle degeneration due to increased muscle contractions or muscle degeneration due to inactivity?
As I thought about it further I wondered if we could avoid degeneration altogether by finding a strength training program that minimizes the forces on the muscle but maximizes muscle growth.
With the help of Keegan and his electrical engineering skills, we came up with an experimental design to study the impact of strength training on dystrophic muscle. During my physical therapy sessions, I received neuromuscular electrical stimulation to retrain my muscles on how to contract and provide a stimulus to prevent further muscle wasting. Keegan and I created four different series of electrical pulses to emulate each of the four types of strength training: endurance, hypertrophy, strength, and power. These series of electrical pulses vary in the number of pulses and their voltage to mimic the number of repetitions and the weight one would use while training at the gym.
Telling the top researchers in skeletal muscle disease that I strength train zebrafish larvae is intimidating. While zebrafish larvae are a well-established model for studying muscle development and disease, no one has looked at it as a potential model for studying how strength training impacts diseased muscle. Every single day I am amazed by the questions that I can answer using the zebrafish model: I use numerous microscopy techniques to study how dystrophic muscle responds to electrical stimulation; I image zebrafish multiple times a day, multiple days a week to track individual muscle fibers; I look at different aspects of muscle structure, including the nerves innervating the muscle and the mitochondria fueling the muscle; I monitor how different genes known to play an important in muscle growth and regeneration are responding to the stimulation.
Research is like a 1000-piece puzzle of a sunset, where all the pieces are different shades of yellow, orange and red. It can be frustrating, it can take more time than we think, and the pieces may not fit together how we thought. However, it is the support from individuals who attend events like the Morgan Hoffmann Foundation Celebrity Pro-Am, who cheer me on via social media, and who continue to advocate for a cure that are making a profound impact. The financial support, the encouragement, and the community make research easier. The grant provided by the Morgan Hoffmann Foundation is allowing me to expand this research to include more models of muscular dystrophy.
No individual with a muscle disease should ever feel like they are fighting this fight alone. We are stronger together. I am incredibly grateful for all the individuals I have met through muscular dystrophy.