November 18, 2019

Cystic Fibrosis and the Ashkenazi Jewish Connection

When California native Stacy Carmona was 10 years old, her 12-year-old best friend died from cystic fibrosis (CF). CF is a rare, life-threatening genetic disease that affects the lungs and pancreas. Carmona also suffers from the disease and her friend’s death awakened her to the horror that her parents had tried to hide from her: the brutal reality of the disease. 

CF is a recessive disease that’s acquired from both parents having a copy of a defective gene that causes CFTR protein to become dysfunctional. Approximately 1 in 25 Ashkenazi Jews are carriers. If both parents are carriers, there is a 1 in 4 chance that each child will inherit the disease.

Carmona inherited the disease from her parents and, at the age of 10, was faced with the question: Would she let CF define the rest of her life or would she live it to the fullest despite an uncertain future?

Today, Carmona is 33, married and expecting her first child. She’s given motivational speeches, defying all expectations people had for her when she was a child. When she was born, the average lifespan of someone with CF was 18. Today people with CF can live to be 34 to 40. Some even live beyond 50.

Stacy Carmona and her husband.

Carmona has managed to live a meaningful life full of purpose and urgency, but it’s a daily struggle because CF causes the body to harbor bacteria because of a genetic mutation that produces a thick, sticky mucus. Over time, the buildup of bacteria causes chronic lung and sinus infections that make breathing difficult and ultimately leads to lung failure. The mucus also causes inflammation in the pancreas, preventing food from being absorbed. It’s estimated that 30,000 people in the U.S. have CF, and although treatments are rapidly improving, there’s still no cure.

There are some promising new advances in CF research, but there’s a catch. 

Approximately 1 in 25 Ashkenazi Jews are carriers. If both parents are carriers, there is a 1 in 4 chance that each child will inherit the disease.

By 2020, medications that correct the basic defect are expected to benefit 90% of the CF population (using modulator drugs that target the defective CFTR protein caused by the most common CF mutation, Delta F508). However, the remaining 10% will be left behind, because they have different mutations not targeted by the treatment. One of these mutations belongs to a class called nonsense mutations, which disproportionately affects Ashkenazi Jews.

Carmona told the Journal the improvement in drug treatments is bittersweet. “The time that it takes to get a medication from test tube to patient can be 10 to 15 years and [cost] a billion dollars. It’s a scary place to be.”

These obstacles are what propelled Emily Kramer-Golinkoff — who has CF — to take the fight for her life into her own hands. In 2011, while working at Penn Medicine and pursuing a graduate degree at the University of Pennsylvania in bioethics, she launched Emily’s Entourage, an organization with a singular focus on nonsense mutations.

Photos courtesy of Emily Kramer-Golinkoff

“I had no grand vision of starting an organization but we felt there was no hope,” she told the Journal. “It was up to us to do something.”

Since its inception, Emily’s Entourage has raised nearly $6 million to fund 17 research projects around the world, accelerating drug research for those with CF nonsense mutations. 

For her work, Emily was named a White House Champion of Change for Precision Medicine in 2015 and was invited to speak at the White House. “We realized there was a whole infrastructure that was broken to even develop future hope for us,” she said.
The work funded by Emily’s Entourage has further significance because nonsense mutations are found in roughly 12% of all genetic diseases, meaning up to 30 million people worldwide could benefit from these drug discoveries. Advancements in treating nonsense mutations in CF can extend to treating certain types of muscular dystrophy, inherited blood disorders, as well as some cancers.

Emily Kramer-Golinkoff; Photos courtesy of Emily Kramer-Golinkoff

With CF becoming a predominantly fatal Jewish disease, much of the advancements are happening in Israel. Dr. Eitan Kerem, head of Hadassah Medical Center’s Pediatric Division in Jerusalem, is regarded as one of the leading doctors in the world specializing in CF, authoring more than 170 papers in the field of pulmonology. “If the gene is defective and the protein which is called CFTR is defective, then there is less hydration and dryness of secretion in these airways in the lungs,” Kerem said in a Hadassah podcast earlier this year.

Today, Carmona is 33, married and expecting her first child. She’s given motivational speeches, defying all expectations people had for her when
she was a child. 

The CF Foundation also has set up a Nonsense and Rare Mutation Initiative (NRMI) to fund research for the 10% left behind. Since 2015, it has funded more than 60 NRMI projects, raising nearly $63 million.

Some of the top research also is coming from a person living with CF. Los Angeles native Jacob Witten is a 26 year-old post-doc at M.I.T. He earned his doctorate in computational biology and now is studying how to use gene editing to cure CF. “If you fix the basic genetic defect then you stop the progression of CF in its tracks,” Witten said of his research.

Jacob Witten; Photo courtesy of Jacob Witten

“He declared from the time he was a little kid that if CF wasn’t cured by the time he was old enough he would cure it himself,” Witten’s mother, Nancy Seid, told the Journal.

Witten works out five to six days a week (five days of running with two days of weight lifting mixed in) and has a high caloric, high-fat diet, which is needed because people with CF have a hard time maintaining weight. He wakes up every day around 6 a.m. and goes for a run. When he comes home he does his vest breathing treatment for half an hour, then showers and arrives at work by 9:30.

Mornings typically require an hourlong breathing treatment in which a vest is worn that inflates and vibrates at high frequencies, breaking up the mucus in the lungs. This routine is then repeated at night. Throughout the day, a person with CF takes roughly 40 to 50 pills, including digestive enzymes with every meal. Everyone presents symptoms differently. For instance, Carmona said she feels like she has a cold every day, and that’s when she’s healthy. Witten, on the other hand, said he has never felt sick. His mother said she believes growing up near the Pacific Ocean may have strengthened his lungs, because the saline in the air provides a protective coating.

Another Jewish CF patient — Jessica Franklin — is also very athletic. She tries to get up at 5:30 a.m. every day and go for a run or take a yoga class, before returning home to shower and take her vest treatment, before arriving at work by 8:30.

Raised in Philadelphia, Franklin graduated from Philadelphia’s Drexel University in 2017 before moving to Tampa Bay, Fla., where she works as a brand ambassador for the Collective Genius company. She has been a public advocate for CF since she was 5 and did her first speaking gig at 10 and on her college graduation cap wrote the words: ‘Your problems are never bigger than your purpose.’

Jessica Franklin. Photo courtesy of Jessica Franklin

“I haven’t had a choice but to be an advocate,” she said. “My parents felt if you’re an advocate then CF will be cured.” 

In 2015, she raised $1 million at a CF fundraising event in Philadelphia.

Carmona also has made advocacy a central part of her life. She is the director of CF patient advocacy at Kroger Specialty Pharmacy, serves on the CF Foundation’s Adult Advisory Counsel, and is a patient representative for the Food and Drug Administration.

Unlike most life-threatening conditions, CF is one of a few diseases where forming community with other sufferers is kept at a distance. Exactly 6 feet apart, to be exact. Any closer and it could potentially be fatal for sufferers.

Witten, however, said, “I don’t really pay attention to the CF community in any way. I’m kind of an outlier in that sense. Especially for having nonsense mutations.” That may be because unlike many CF sufferers Witten is considered high functioning with no history of hospitalizations or ever presenting major symptoms. 

However, “With respect to infection, I’m extra paranoid,” he said, because a person with CF who is as healthy as Witten can still be vulnerable to the more pronounced symptoms if he comes in contact with someone who is sick. It requires him to take meticulous care of himself and be aware of his surroundings always. Though, generally, he said being outside is not a major concern, which explains how he’s run numerous half-marathons and played competitive sports his whole life.

Franklin also said she is currently in good health. She has 90% lung function, which is considered excellent, but added, “I’ve had now six sinus surgeries,” including a recent surgery that required her to take two months off work. Doctors had to make incisions into four bones behind her eyes to drain the mucus. “My face was basically turning into Medusa,” she said. 

Despite this ordeal, she said her condition is considered mild, which has enabled her to remain physically active.

Carmona, though has had to be much more cautious with her physical activity. “My best day is like my husband’s worst day,” she said. “Now that I’m pregnant I’m being very cautious. If I could bubble wrap myself and not leave the house for all of flu season, I would.” She has the benefit of working from home, but acknowledges that as a student, she was always conscious of who had a bad cough.

By the time Carmona was 18, she already had endured 12 sinus surgeries, two stomach surgeries and more hospitalizations than she can count. She knows to take every threat seriously. For instance, she explained that when her husband is sick, he has to sleep in the guest room, and when she travels she has to wear a mask. Catching a simple cold can mean weeks in the hospital and rounds of IV antibiotics. Franklin and Witten don’t have to wear masks outside because of their strong lung function, although Franklin said she always wears one on airplanes.

“I had no grand vision of starting an organization but we felt there was no hope. It was up to us to do something.”
— Emily Kramer-Golinkoff

Carmona recently was diagnosed with CF-related diabetes and said that monitoring her blood sugar levels and administering insulin has been a unique challenge. She’s spent her entire life perfecting her CF routine, but with a child on the way, she knows she must plan meticulously in advance to navigate her approach to parenthood, as people with CF require a lot of rest.

Fortunately, she has a supportive family 15 minutes away in Orange County, while Witten’s and Franklin’s jobs required them to move thousands of miles away from their families. 

In 2014, Carmona accomplished one of her dreams of giving a TEDx Talk about living with CF. What starts as a bleak tale evolves into an inspiring and captivating speech, evoking laughter from a responsive audience.

Carmona, Witten and Franklin spoke to the Journal separately about their experiences living with CF. And that “separateness” is no coincidence. In fact, it’s a defining feature of the disease. People with CF live in a unique oasis. Unlike most life-threatening conditions, it is one of a few diseases where forming community with other sufferers is kept at a distance. Exactly 6 feet apart, to be exact. Any closer and it could potentially be fatal for sufferers. That’s because CF sufferers can pass dangerous bacteria between them. It makes the CF experience a mostly solitary one, relying on the grace of allies to provide support. With the emergence of social media, however, people with CF are rallying together as digital families, but meeting in person remains rare.

And because sufferers are aware that their life spans are likely to be shorter than most, even if they can’t meet in groups, they pursue their personal passions with a sense of urgency. 

Carmona said that her illness has given her a greater appreciation of life, and that her story has made those around her find gratitude in every breath. “Accomplishing milestones is so much more meaningful because I have to work so much harder to get there,” she said.

Her father, Paul Motenko, has become a committed advocate for CF research, making his daughter’s illness his life’s mission. “I believe that, if the philanthropic Jewish community becomes aware of this situation, we can generate significant support for this area of research,” he said. Motenko helped organize a cultivation event to support CF research that took place on Nov. 5 in Los Angeles. 

“The purpose of the event is to create awareness in the Jewish community about this very important situation,” Motenko said. “CF is more prevalent [among Ashkenazi Jews] than many of the more commonly-known Jewish genetic diseases, like Tay-Sachs.” 

“It’s given me a very different perspective on life because I’ve been faced with my own mortality my entire life,” Carmona said. “The big takeaway with CF is how we make our time valuable.”

For Kramer-Golinkoff, it’s also about spreading a message of hope. “Our dream,” she said, “is that we will find a cure for CF and then be able to move on to another rare disease and then apply all of our learning to another.” 

With continued research, CF will hopefully one day stand for “Cure Found.”

For more information about cystic fibrosis and Emily’s Entourage, click here. More on the CF Foundation’s can be found on their website. 


Peter Fox is a New York-based writer. His work has appeared in The Jerusalem Post, Tablet Magazine and The Forward. Follow him on Twitter @thatpeterfox.