A Story of Hope: Medical Science Does Work Miracles!

While Dr. Catalona’s life’s work involves prostate cancer, he is always intrigued by breakthroughs in other areas of medicine. One such breakthrough came into focus after a patient told Dr. Catalona that his daughter was devastated recently to have lost all her hair, including her eyebrows and eyelashes, a condition called alopecia, an autoimmune skin disease in which the immune system attacks hair follicles, causing hair to fall out in clumps and leading to complete baldness.

When hearing this, Mrs. Catalona asked her dear friend, whose daughter, Caroline, had suffered through her childhood and teenage years with this condition, if Caroline would be willing to share her story with QUEST readers. Caroline graciously agreed. At age 10, Caroline began to develop bald patches. In the middle of the sixth grade, all her hair, as well as some of her eyebrows and eyelashes, fell out. As with many medical conditions, the diagnosis, treatment, and coping were complex journeys. Consulting different physicians over the years led to injections into her scalp, restrictive diets, and yoga to manage stress, all of which were ineffective.

During this period of her life, she continued her “job” of being a junior high and high school student, not hiding at home but being enthusiastic and vivacious, even leading her school’s cheerleading squad. Outwardly, Caroline was irrepressible, but, as we all can appreciate, she still really wanted to have her hair. Credit goes to her family’s commitment to not giving up but continuing their search for an effective treatment for alopecia, which they found.

Fortunately, new drugs were developed from modern biomedical research discoveries. Dr. Catalona wanted to know what the “miracle” drug was.

When Caroline was seventeen, a dermatologist four hours away from their home prescribed tofacitinib, an off-label treatment for rheumatoid arthritis. Her hair started growing back! In 2022, she switched to baricitinib, the first FDA- approved drug for alopecia. Caroline’s mother sent photos of her now: “…see how well her meds have worked! As you know, for several years, she was completely bald.”

Dr. Catalona investigated how this miracle drug came about. In 1993, Dr. Paul Changelian, a Pfizer’s immune suppression group scientist, sought a new way to prevent organ transplant rejection. Always on the lookout for new ideas, particularly ones related to suppressing an overactive immune system (a hallmark of diseases like psoriasis and rheumatoid arthritis as well as organ rejection), he decided to attend a summer meeting in Vermont where the world’s leading scientists gathered to discuss cutting-edge research. While at this meeting, he ran into an old acquaintance, Dr. John O’Shea, a researcher at the National Institutes of Health (NIH).

As scientists do, Paul and John discussed their current projects. When Paul told John that he was searching for a drug that could produce immune suppression, John mentioned that his lab had just discovered a particular enzyme called JAK, that could play a role in immune function. Establishing a collaborative research agreement, Pfizer and the NIH launched the project.

Working diligently together on this project, by 2000, they developed a drug, tofacitinib. Human studies proved exciting. The drug could almost completely clear psoriatic skin patches, called plaques, in patients with severe psoriasis. However, they found the most compelling results in rheumatoid arthritis patients for whom the currently used biological drugs were ineffective. In 2011, the FDA approved tofacitinib for treating adult patients with rheumatoid arthritis.

Subsequently, physicians at the Cleveland Clinic searched their medical records for alopecia patients treated with tofacitinib and found it stimulated hair regrowth. Building on these findings, Eli Lilly researchers developed another JAK enzyme blocker, baricitinib. The FDA initially approved the pill to treat rheumatoid arthritis, but they found that it also blocked the same enzyme that triggers hair loss. In 2022, the FDA approved baricitinib for treating severe alopecia.

JAK enzyme blockers have now gained traction for treating various other autoimmune diseases, including psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, and ulcerative colitis. In 2022, the FDA approved baricitinib also for treating hospitalized COVID-19 patients who require supplemental oxygen therapy, cutting the risk of death by about 20%. Building on the clinical success of first-generation JAK inhibitors, second- generation compounds that claim to be more selective are currently undergoing development and proceeding to clinical trials.

The mechanisms underlying diseases are like giant, complicated jigsaw puzzles. In Caroline’s case, biomedical researchers conferring in the Vermont woods worked together, identifying and assembling the key pieces of the puzzle, leading to surprising, beneficial discoveries.

As for Caroline, she was able to start college with a full head of hair and now is looking forward to graduating from college, taking some well-deserved time to relax, and pondering her next steps. Regardless of the disease, like Caroline, we must “keep hope alive.”