RARE Daily

A 37-Year Path to a Diagnose, but Now a Drug May Be Two Weeks Away

April 15, 2024

It took Courtney Ampezzan 37 years to get a correct diagnosis for her condition, an unusual length of time even by rare disease standards.

Ampezzan had long been recognized as having a common variable immunodeficiency, a catchall term for people with an immunodeficiency without an identified cause.  She had genetic testing performed in 2019 after her long-time doctor retired and she began getting care with a new specialist. It was then that she was diagnosed with WHIM syndrome, an ultra-rare immunodeficiency driven by a genetic mutation.

WHIM is an acronym for warts, hypogammaglobulinemia, infections, and myelokathexis. It is caused by reduced mobilization and trafficking of white blood cells from the bone marrow due to over-signaling of the CXCR4/CXCL12 pathway. People with WHIM syndrome characteristically have very low blood levels of neutrophils and lymphocytes, key players in the immune system. People with WHIM syndrome suffer from frequent, recurrent infections with a high risk of lung disease, refractory warts from underlying human papillomavirus infection, limited antibody production due to low levels of immunoglobulin, and an increased risk of developing certain types of cancer.

While patients with the condition have been treated with intravenous immunoglobulin to normalize the immune system—Ampezzan has gotten intravenous immunoglobulin ever since the age of 3— there is no available treatment for WHIM syndrome today.

For Ampezzan, living with WHIM syndrome has meant that exposure to pathogens that might cause a minor illness, if anything, for most people, can send her to the hospital. She typically has three to four hospitalizations a year.

Now 42, Ampezzan is hopeful her diagnosis may lead to a significant change in care. While it’s connected her with a community of other people with WHIM syndrome and provided her with a new perspective on her condition, she may soon have an approved therapy to treat the condition. The U.S. Food and Drug Administration is expected to decide whether to approve X4 Pharmaceuticals’ mavorixafor by the end of April.

Mavorixafor is an experimental small-molecule antagonist of CXCR4 being developed as a once-daily oral therapy to correct the dysfunction resulting from the underlying causes of WHIM.

Ampezzan, who lives in North Yarmouth, Maine, about 18 miles north of Portland, has grown used to altering her life because of her condition. She had to give up her job as an administrative specialist for MaineHealth. Plans often need to be cancelled— whether it’s birthday celebrations, weddings, or vacations. And she’s had COVID four times.

“Every day is a challenge because I don’t have a strong immune system. So, when I’m exposed to anything, it’s a risk,” she said. “I have to be very calculating and prepared if I’m ever in crowds or if I go anywhere or do anything to kind of always have that in the back of my mind.”

She said she needs to be very proactive and very protective about what she chooses to do. Making a choice to do something as simple as going outside is a risk for her. If she makes plans to see friends and do those things, there are many things she needs to consider. During the pandemic, she needed to move back in with her parents and keep her distance from her husband, who is a police officer and first responder. She wasn’t allowed to leave her parents’ house or see her husband for months.

She hopes an approved drug will mean the ability to lead a more normal existence where she won’t be consumed by her illness.

“If I could feel surer that I’m healthier and that my health is in a better place, then maybe I can do more things with my life and kind of engage more in the world around me, which would be lovely,” she said. “If there’s a possibility that I won’t get as sick as often, I might be able to relax a little bit, which would sure feel nice to not always have my shoulders as earrings. I’m always waiting for the next thing and being prepared. [It would be nice] to be able to relax and say, ‘I’ve been less sick for X amount of time, so maybe I can get in more of a groove where I can experience more of the life that I want.’”

Photo: Courtney Ampezzan

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