Emily Kramer-Golinkoff lives under the shadow of advanced cystic fibrosis, a challenging condition that drains the vitality from everyday activities such as walking or bathing. The disease, a frequent cause of death in the genetic spectrum in the U.S., affects 40,000 people nationwide. However, Kramer-Golinkoff’s situation is complicated by a rare genetic variant, rendering the typical cystic fibrosis medications, effective for 90% of patients, ineffective for her.
This struggle highlights a broader issue seen in genetic disorders where scientific advancements have pinpointed their intricate origins and paths towards potential treatments. Unfortunately, individuals with uncommon genetic mutations often face limited treatment options and grim prognoses. Many are now placing their hopes in experimental gene therapies.
“We feel pure joy for friends who have found relief, but it’s hard being left behind,” says Kramer-Golinkoff, aged 40. A complicating factor beyond science is market demand. Pharmaceutical companies are incentivized to develop treatments targeting the more common genetic mutations.
“You need a large enough patient group in a major market to capture a company’s interest,” notes Dr. Kiran Musunuru, a gene editing specialist at the University of Pennsylvania, who refers to this as “mutational discrimination.” As a response, charities such as Emily’s Entourage, which Kramer-Golinkoff co-founded, are working to bridge this gap. Their fundraising is fueling gene therapy research that could help those regardless of their mutation.
Though these therapies won’t be available for years, “having these trials provides us with hope,” Kramer-Golinkoff remarks. The availability of current cystic fibrosis treatments presents a mixed picture.
Diagnosed at just six weeks old, Kramer-Golinkoff battles cystic fibrosis, a condition where thick mucus clogs the body due to a malfunctioning CFTR protein, leading to lung and other organ complications. Over time, despite her efforts, her condition has worsened.
In better health, she pursued a master’s in bioethics, worked, traveled, and enjoyed social life. Now, complications like CF-related diabetes have surfaced. She faces frequent infections and, since the pandemic, has lived in seclusion with her parents in the Greater Philadelphia area. “CF is a monstrous disease,” she reflects.
Others with cystic fibrosis enjoy health improvements thanks to “CFTR modulator” therapies, which aid those with the most prevalent mutation by correcting protein malfunctions. These therapies enhance lung function, respiratory symptoms, and overall quality of life.
However, not everyone benefits; those with rare mutations or unstudied genetic causes, particularly in underrepresented regions and populations, often miss out. Genetic testing companies strive to broaden ethnic diversity in screenings, but disparities persist. For example, African populations have limited data, impacting Black cystic fibrosis patients who are more likely to fall within the 10% not benefiting from existing treatments.
Research envisions a solution with “mutation agnostic” gene therapies for various diseases, including cystic fibrosis and retinal disorders. The Cystic Fibrosis Foundation notes that 14 gene therapies are in development targeting all mutations, aiming to provide corrected CFTR genes to cells, enabling functional protein production regardless of the mutation type.
One promising gene therapy, financially supported by both the foundation and Emily’s Entourage, has been initiated by Spirovant Sciences. The first trial participant began treatment in November during a 53-week study at Columbia University to explore the therapy’s safety and duration in the lungs.
Despite worsening health conditions, Kramer-Golinkoff remains hopeful about her future. Her current health challenges, characterized by reduced lung function, kidney problems, pulmonary hypertension, diabetes, and a regimen of daily medications, demand careful energy management. “Managing limited energy is tough when big dreams and meaningful work await,” she shares.
“We are incredibly excited about the potential of gene therapies. Their arrival can’t come soon enough.”