Two lifesaving discoveries help four generations of women
This story was originally posted on Center Times Plus on February 12, 2019.
Her great-grandmother volunteered in groundbreaking cholesterol research at UT Southwestern. Now, 9-year-old Zoe Allen is benefiting from that decision.
Four generations of women, who all have the same hereditary condition – familial hypercholesterolemia – form a story interwoven with the discovery of new treatments that have benefited millions of people. The disorder can lead to aggressive and premature cardiovascular disease.
In 1987, Kathryn Geddie was a 33-year-old mother of two. At her annual physical, she told her doctor that her mother had extremely high cholesterol levels at a young age. After testing, Mrs. Geddie learned she had the same condition and began taking cholesterol-lowering statin drugs.
“My mother is the reason that I was tested. My physician began treating me in 1987 because my cholesterol was in the upper 300s,” remembered Mrs. Geddie, now 64, of Sunnyvale, Texas.
Mrs. Geddie’s immediate concern drove her to have her then 11-year-old daughter, Shanon, tested. Despite her young age, Shanon’s cholesterol level was soaring at 400 milligrams per deciliter (mg/dL). Normal range is less than 200. Little did they know then that their shared struggle with high cholesterol would lead them on a road to reverse the disease – one paved by the generation just before.
Statin discovery
In the early 1980s, Mrs. Geddie’s mother, Estelle, took part in leading-edge research at UT Southwestern in which Professors of Molecular Genetics Drs. Michael Brown and Joseph Goldstein were investigating why people develop high cholesterol. They identified the basic mechanism of cholesterol metabolism, which led to their 1985 Nobel Prize in Physiology or Medicine.
Soon after their discovery, statins were developed to lower cholesterol and help prevent heart disease. Thousands of adult patients benefited. However, there were unknown risks for children. As a precaution, parents were advised to treat their children with statins only after puberty.
Familial hypercholesterolemia affects how the body processes cholesterol, raises the risk of heart disease, and increases the risk of suffering an early heart attack or stroke. Knowing her mother’s connection to research, Mrs. Geddie returned to UT Southwestern and enrolled her 11-year-old daughter in clinical trials with a pediatric cardiologist.
“I remember I had to eat some weird grains and bad-tasting medicine. I was a sixth- or seventh-grader and didn’t like taking the medicine,” recalls Shanon Allen, now a 42-year-old married mother of two who lives in Allen, Texas. “I remember going to UT Southwestern on Saturdays to do stress tests.”
When she turned 16, Mrs. Allen was old enough to begin taking statins, just like her mom. She had no side effects while she was young. “I was off statins for two to three years while I was trying to get pregnant, during pregnancy, and while I was breastfeeding. During this time, my doctor and I monitored my cholesterol and weighed the risks and benefits of statins.”
With time, Mrs. Geddie’s story became more complicated.
Changing course
“Three decades after I started taking them, the highest dose statin would no longer work,” Mrs. Geddie recalled. “My doctor added another drug to my high dose statin. My muscles stopped working and I stopped treatment.”
Then her doctor added a new drug to her regimen called a PCSK9 inhibitor – one of a class of drugs developed from game-changing research at UT Southwestern.
Renowned UTSW geneticist Dr. Helen Hobbs – a Professor of Internal Medicine and Molecular Genetics, Director of the Eugene McDermott Center for Human Growth and Development, and a Howard Hughes Medical Institute Investigator – made the surprising discovery of the effect of PCSK9 inhibitor mutations while studying data from the Dallas Heart Study.
Early in her career, Dr. Hobbs worked as a postdoctoral fellow in the laboratory of Drs. Brown and Goldstein. Pioneering research by Dr. Hobbs and her colleague, Dr. Jonathan Cohen, Professor of Internal Medicine and in the Center for Human Nutrition and the McDermott Center, has provided novel insights into the genetic basis of cholesterol metabolism, which together with the work of other investigators has led to the development of this new class of agents to treat hypercholesterolemia, approved by the FDA in 2015.
The PCSK9 inhibitor treatment helped Mrs. Geddie, but not entirely. Getting it covered by insurance was difficult. Still seeking a balance between managing her risks and the side effects of medication, Mrs. Geddie was referred to cardiologist Dr. Parag Joshi, Assistant Professor of Internal Medicine at UT Southwestern. She was thrilled to have access to research that helps people who don’t benefit from the standard treatment. She was hopeful for a solution.
Dr. Joshi’s work in preventive cardiology helps patients avoid cardiovascular events, such as heart attack or stroke. “When Kathryn came to me, she was seeking answers not only for herself, but also for her daughter and granddaughter,” he said.
In November 2018, Dr. Joshi recommended confirming Mrs. Geddie’s diagnosis with genetic testing.
All in the family
A simple saliva test confirmed Mrs. Geddie’s diagnosis of familial hypercholesterolemia. The results empowered her with knowledge while giving cause for her insurance to cover the treatment.
“I need to know I’m doing everything I can to manage my health as I age. I have the gene. It gives me peace of mind to know I’m maintaining my health,” Mrs. Geddie said.
Research that began with Drs. Brown and Goldstein and continued with Drs. Hobbs and Cohen has made a dramatic difference in her treatment. “Neither the statin nor the PCSK9 inhibitor alone were doing the trick. It was a combination of a dose of statin that she could tolerate plus the PCSK9 inhibitor that created an additive effect and got her cholesterol down to levels she had never seen before,” Dr. Joshi said.
“We’re proud to have a personal connection to UT Southwestern research that impacts so many,” Mrs. Geddie said.
Mrs. Allen and her daughter, Zoe, are both waiting for their own genetic testing results. “Now we want to find the right treatment for Zoe,” Mrs. Allen said.
Their family is hoping for the best possible future, and they’re thankful to Estelle. “If my grandmother had not taken part in the study, we might not have known we had the problem,” Mrs. Allen said.