\n Emily Kramer-Golinkoff, who has cystic fibrosis caused by a rare genetic mutation, is shown during a trip to Maine.
\n Emily\u2019s Entourage via AP\n <\/p>\n
Emily Kramer-Golinkoff can\u2019t get enough oxygen with each breath. Advanced cystic fibrosis<\/a> makes even simple things like walking or showering arduous and exhausting.<\/p>\n She has the most common fatal genetic disease<\/a> in the U.S., which afflicts 40,000 Americans. But her case is caused by a rare genetic mutation<\/a>, so medications that work for 90% of people with cystic fibrosis won\u2019t help her.<\/p>\n The same dynamic plays out in other genetic conditions. Stunning advances in genetic science have revealed the subtle, insidious culprits behind these brutal diseases and have started paving the way for treatments. But patients with these exceedingly rare mutations have fewer options and poorer prospects than those with more typical forms of these diseases \u2014 and many are now pinning hopes on experimental gene therapies.<\/p>\n \u201cWe feel such pure joy for our friends who have been lifted from this sinking ship,\u201d said Kramer-Golinkoff, 40. \u201cBut we just feel so eager and desperate to join them. It\u2019s really hard to be in this minority of people left behind.\u201d<\/p>\n It’s not just science that is working against these patients, it’s market forces. Drug companies are naturally going to look for medications that target the most common mutations.<\/p>\n \u201cYou need a sufficiently large number of patients in a major market in order for a company to be interested in going forward,\u201d said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert. What it amounts to, he says, is \u201cmutational discrimination.\u201d<\/p>\n Charities \u2014 including a nonprofit Kramer-Golinkoff co-founded called Emily\u2019s Entourage \u2014 are trying to overcome this barrier. Fundraising efforts have helped jump-start gene therapy that could help patients regardless of mutation.<\/p>\n While it likely won’t be available for years, \u201cjust to have these therapies in trials provides so much hope,\u201d Kramer-Golinkoff said.<\/p>\n Current treatments for genetic diseases don’t help everyone<\/strong><\/p>\n Kramer-Golinkoff was just six weeks old when she was diagnosed with cystic fibrosis, which causes thick, sticky mucus to build up in the body.<\/p>\n It occurs when the so-called CFTR protein is not made or not made correctly, allowing chloride to become trapped in cells, meaning water can’t keep the cell’s surface hydrated. Mucus buildup can lead to damage, blockages and infections in the lungs and other affected organs.<\/p>\n \u201cAs I\u2019ve gotten older \u2026 my CF has gotten worse, despite all my best efforts to delay it,\u201d Kramer-Golinkoff said.<\/p>\n Before her illness got so bad, she was able to earn a master\u2019s degree in bioethics at the University of Pennsylvania, work, travel and spend time with friends. But she eventually developed CF-related diabetes and other problems. She\u2019s prone to infections, and since the pandemic has lived with her parents in isolation in Greater Philadelphia.<\/p>\n \u201cCF is a real monster of a disease,\u201d she said.<\/p>\n Meanwhile, others with the condition have seen vast improvements in their health with \u201cCFTR modulator\u201d therapies that work for people with the most common mutation, correcting the malfunctioning protein. Research shows they dramatically improve lung function, respiratory symptoms and patients\u2019 overall quality of life.<\/p>\n Besides not working for people with rare mutations, these treatments are unavailable to patients whose disease-causing mutations aren’t known or fully understood. Mutations may be unknown because of a lack of genetic testing in places such as developing nations, or understudied because they are uncommon or difficult to detect.<\/p>\n Genetic testing companies such as GeneDx have made some headway in screening more people of diverse backgrounds, but inequities remain.<\/p>\n For example, comprehensive data about cystic fibrosis is scarce among African populations \u2014 affecting people who live on the continent as well as those who trace their ancestry there. Research shows<\/a> Black cystic fibrosis patients are more likely than their white counterparts to be among the 10% who don\u2019t benefit from modulator therapies.<\/p>\n Can a gene therapy work no matter the mutation? <\/strong><\/p>\n While there\u2019s little chance of changing market dynamics, researchers said, one solution is to develop \u201cmutation agnostic\u201d gene therapies targeting all patients with a disease. This approach is being tried in diseases of the retina as well as cystic fibrosis.<\/p>\n \u201cThere\u2019s a huge push to develop these therapies,\u201d said Dr. Garry Cutting of the Johns Hopkins Cystic Fibrosis Center.<\/p>\n