Rare Genetic Conditions: The Hope and Hurdles of New Treatments

The world of genetic medicine is advancing rapidly, but not everyone is benefiting equally. People like Emily Kramer-Golinkoff, who has a rare form of cystic fibrosis, are often left behind. This disease, the most common fatal genetic condition in the U. S. , affects around 40, 000 Americans. However, Kramer-Golinkoff's specific genetic mutation means that the medications helping 90% of cystic fibrosis patients do not work for her. This is a common issue in genetic diseases. While science has made incredible strides, those with rare mutations often have fewer treatment options and a bleaker outlook. Many are now hoping for experimental gene therapies to change their situation. The challenges go beyond just science. Market forces also play a significant role. Drug companies focus on the most common mutations because it makes business sense. "You need a sufficiently large number of patients in a major market in order for a company to be interested in going forward, " said Dr. Kiran Musunuru, a gene editing expert. This means that patients with rare mutations often face "mutational discrimination, " a term used to describe the lack of treatment options for those with less common genetic variations. Charities are stepping in to bridge this gap. Emily's Entourage, a nonprofit co-founded by Kramer-Golinkoff, is one such organization. They are raising funds to support gene therapy research that could help patients regardless of their specific mutation. While these therapies are still in the trial phase and may not be available for years, they offer a glimmer of hope. "Just to have these therapies in trials provides so much hope, " Kramer-Golinkoff said. The current treatments for genetic diseases do not work for everyone. Cystic fibrosis, for instance, occurs when the CFTR protein is not made or not made correctly. This leads to thick, sticky mucus buildup in the body, causing damage and infections in the lungs and other organs. Kramer-Golinkoff, diagnosed at just six weeks old, has seen her condition worsen over time, despite her best efforts to manage it. She has developed CF-related diabetes and other complications, making daily life a struggle.

Meanwhile, others with cystic fibrosis have seen significant improvements with "CFTR modulator" therapies. These treatments work for people with the most common mutation, correcting the malfunctioning protein and improving lung function and overall quality of life. However, these treatments do not help those with rare mutations or those whose disease-causing mutations are not known or fully understood. Genetic testing companies have made some progress in screening more diverse populations, but inequities remain. Comprehensive data about cystic fibrosis is scarce among African populations, and Black cystic fibrosis patients are more likely to be among the 10% who do not benefit from modulator therapies. One potential solution is the development of "mutation agnostic" gene therapies. These therapies aim to help all patients with a disease, regardless of their specific mutation. This approach is being tried in diseases of the retina as well as cystic fibrosis. "There’s a huge push to develop these therapies, " said Dr. Garry Cutting of the Johns Hopkins Cystic Fibrosis Center. Most experimental gene therapies in the pipeline for cystic fibrosis aim to help patients with any mutation, delivering a new, correct version of the CFTR gene to cells. One such treatment, partially funded by the Cystic Fibrosis Foundation, is being tested in a clinical trial at Columbia University. Kramer-Golinkoff remains optimistic about her future, despite her worsening condition. She is living with 30% lung function and depends on insulin for her diabetes, but she is excited about the promise of gene therapies. "They can’t come soon enough, " she said.

Actions