Struggling to Breathe: The Aspirations of Emily Kramer-Golinkoff
Rare genetic disorders may find fewer victims due to advancements in medicine, yet a sense of optimism arises.
Emily Kramer-Golinkoff can't draw in enough oxygen with each breath. Her advanced cystic fibrosis makes even simple tasks like walking or showering an uphill battle. She's one of 40,000 Americans suffering from this devastating genetic disease, but her case is unique due to a rare genetic mutation. This means that medications that work for the majority of cystic fibrosis patients can't help her.
She's not alone in this predicament. Many genetic conditions are seeing remarkable advancements in scientific research, yet patients with these rare mutations find themselves with fewer options. They're pinning their hopes on experimental gene therapies that aim to help victims of all mutations.
"We feel such sheer joy for our friends who have been saved from this sinking ship," said Kramer-Golinkoff, 40. "But we just feel so eager and desperate to join them. It's incredibly hard to be in this minority left behind."
It's not only science that's working against these patients; it's market forces. Drug companies prefer to invest in medications that target common mutations.
"You need a substantial number of patients in a significant market for a company to show interest," said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert. "What it boils down to is 'mutational discrimination.'"
Charities are trying to overcome this barrier. Emily's Entourage, a nonprofit Kramer-Golinkoff co-founded, is among them. Fundraising efforts have kick-started gene therapy trials that could assist patients regardless of their mutation.
While it'll likely take years for this therapy to become available, "just to have these therapies in trials provides so much hope," Kramer-Golinkoff said.
Kramer-Golinkoff was diagnosed with cystic fibrosis at six weeks old. The disease causes thick, sticky mucus to build up in the body, leading to damage, blockages, and infections in the lungs and other organs. As she's grown older, her cystic fibrosis has worsened despite her best efforts to slow its progression.
Before her health deteriorated, she was able to earn a master's degree in bioethics at the University of Pennsylvania, work, travel, and spend time with friends. But she eventually developed cystic fibrosis-related diabetes and other complications. Since the pandemic, she's been living in isolation with her parents in Greater Philadelphia.
"Cystic fibrosis is a real beast of a disease," she said.
While others with the condition have seen significant improvements in their health, Kramer-Golinkoff doesn't respond well to existing CFTR modulator therapies that work for common mutations. Research indicates these treatments can dramatically improve lung function, respiratory symptoms, and overall quality of life, but they don't help people with rare or unknown mutations.
Genetic testing companies like GeneDx are making headway in screening more people of diverse backgrounds, but inequities remain. For instance, comprehensive data about cystic fibrosis is scarce among African populations. Research indicates that Black cystic fibrosis patients are more likely than white counterparts to be outside the 90% that benefit from modulator therapies.
One potential solution is developing "mutation-agnostic" gene therapies that target all patients with a disease. These therapies aim to work universally across all mutations by introducing a healthy CFTR gene into patients' cells, bypassing the need for mutation-specific targets. This approach is being attempted in diseases like CF and retinal diseases such as retinitis pigmentosa.
Researchers are optimistic about the field's progress. There are currently 14 experimental gene therapies in development for CF, many focusing on CFTR gene delivery. Clinical trials, like Spirovant Sciences' therapy, which received partial funding from Emily’s Entourage, are underway.
As Kramer-Golinkoff's condition worsens, she remains hopeful. Currently, she's living with 30% lung function, has kidney issues, and high blood pressure in her lungs. She relies on insulin for her diabetes and takes numerous medications daily. "You have to make thoughtful decisions ... throughout the day on how to use your limited energy," she said. "And that's extremely difficult to do when you have ambitious goals and a life you want to live."
"We're incredibly excited about the promise of gene therapies," Kramer-Golinkoff said. "They can't come soon enough."
- Emily Kramer-Golinkoff, despite having a rare genetic mutation, struggles with her advanced cystic fibrosis, making simple tasks challenging.
- Kramer-Golinkoff's case is unique because medications that help most cystic fibrosis patients don't work for her due to a rare mutation.
- Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert, explains that drug companies primarily invest in medications that target common mutations, creating a form of 'mutational discrimination'.
- Emily's Entourage, a nonprofit co-founded by Kramer-Golinkoff, is raising funds to initiate gene therapy trials that could help patients regardless of their mutation.
- The advancements in scientific research for genetic conditions offer hope, but patients with rare mutations often find themselves with limited options.
- Researchers are optimistic about the progress in developing mutation-agnostic gene therapies for diseases like cystic fibrosis and retinal diseases, bypassing the need for mutation-specific targets.
- Kramer-Golinkoff remains hopeful about the potential of gene therapies, as they could significantly improve her health and quality of life, while managing her chronic diseases and mental health amidst the looming pandemic and isolation.
