Anna’s Story: A Patient’s Role in Furthering Friedreich’s Ataxia Research

By Lauren Ingeno and Abny Santicola

Kristin Morrow first noticed an issue with her daughter Anna's balance during field hockey practice in 2015. Anna, who was 9 years old at the time and is now 18, had always been a natural athlete, so it struck Kristin that her daughter was struggling to get through a basic warm-up drill without tripping. In the weeks that followed, Kristin saw that Anna was stumbling during walks to school.

"This was a kid who rode a bike at age 4," Kristin said. "She was very physically able, and I started to notice her regressing."

Following a visit with a pediatric neurologist and undergoing confirmatory genetic testing, Anna received a distressing diagnosis: Friedreich's ataxia (FA), a rare neurodegenerative disease that causes progressive damage to the nervous system. Symptoms typically begin in adolescence and worsen throughout a patient's lifetime.

Soon after Anna's diagnosis, a family friend recommended the Friedreich's Ataxia Program at Children's Hospital of Philadelphia, which was two hours from the family's home in Baltimore. Led by David Lynch, MD, PhD, the program is the largest of its kind in the world, providing diagnostic testing and lifelong disease management for patients.

The program is part of CHOP's Friedreich's Ataxia Center of Excellence, a collaboration of leading experts committed to promoting FA research and clinical care. FA research at CHOP has led to a greater understanding of the metabolic dysfunction underlying FA, the creation of an FA patient database, and the identification of more than 20 drug candidates that represent potential new therapies.

Since her first visit with Dr. Lynch in 2015, Anna has received care at the Center and, as a study participant, played a pivotal role in the search for FA treatment.

In the winter of 2023, Anna's family received potentially life-changing news: The U.S. Food and Drug Administration approved omaveloxolone (Skyclarys™, Reata Pharmaceuticals), the first treatment for FA. (Anna did not participate in the omaveloxolone trial.)

The approval follows more than a decade of research led by Dr. Lynch and colleagues. Now, Anna and other adolescents like her around the country have access to a once-a-day oral pill that can slow the progression of the debilitating disease.

"These are individuals in high school and college who are losing the ability to walk, which makes those years of life much tougher," Dr. Lynch said. "Even forestalling that disease progression by a few years could be crucial to their development."

Navigating the Long Road to Drug Approval

FA affects the spinal cord, peripheral nerves, and the brain, resulting in uncoordinated muscle movement, poor balance, difficulty walking, changes in speech and swallowing, and a shortened lifespan. More than 95% of patients are wheelchair-bound by the time they reach their mid-40s.

FA is caused by a severe deficiency of the frataxin protein inside the mitochondria, the cell's powerhouse. Without frataxin, the body can't produce adenosine triphosphate (ATP), which leads to nervous system damage.

More than a decade ago, Dr. Lynch and colleagues at CHOP were investigating the possibility of targeting the NRF2 pathway, which protects the body against oxidants, as a potential FA treatment. Simultaneously, Texas-based Reata Pharmaceuticals Inc. was investigating a drug that would activate NRF2 — as a potential treatment for cancer. Dr. Lynch and colleagues from the Friedreich's Ataxia Research Alliance (FARA) flew to Plano, Texas, for a meeting with the company, suggesting that it would be worthwhile to pursue the same drug in patients with FA.

With access to the largest number of FA patients in the country, CHOP worked with the company to organize the multisite clinical trials to study omaveloxolone and served as a lead clinical trial site. CHOP enrolled 55 patients between the ages of 16 and 44 into two phases of the clinical trial, which tested the drug's safety and efficacy.

“College students who were so fatigued that they couldn't make it through two classes a day — because fatigue is a big part of FA — after nine months on the treatment, they could make it through multiple classes per day while working a part-time job.” - David Lynch, MD, PhD

The drug was shown to be effective at improving symptoms and slowing the progression of the disease, essentially sending patients back in time, on average, by a year or two and keeping them at that disease state for three to four years.

"Patients realized they could do things they couldn't do a year ago," Dr. Lynch said. "College students who were so fatigued that they couldn't make it through two classes a day — because fatigue is a big part of FA — after nine months on the treatment, they could make it through multiple classes per day while working a part-time job."

Motivated for a Bright Future

Anna has participated in multiple research studies and clinical trials, including Dr. Lynch's natural history study, which is funded by FARA. Every year, Anna, her three siblings, and their parents travel together to Philadelphia to participate in rideATAXIA, an annual bike ride to raise funds for FARA's mission to treat and cure FA through research.

For a study focused on the impact of exercise, Anna followed a specific strength training regimen. Participating in that study helped her establish an exercise routine, and showed Anna how maintaining her mobility and stamina could help slow the progression of FA symptoms.

"The experiences that we have been provided through the Center of Excellence have been absolutely amazing," Kristin said. "There is so much progress being made. We feel so fortunate to be able to participate."

Anna, a junior at an all-girls high school, is passionate about sports and loves to stay busy. After school, she serves as the manager for the lacrosse, basketball, and field hockey teams. She plans to go to college and major in a sports-related field, and she would like to continue participating in FA research and advocacy efforts.

"I think she feels proud to participate in the studies," Kristin said. "She feels she's doing her part to further the research."