DNA day is a time to celebrate, and to hope for the future. New and promising PCSK9 inhibitor treatments were approved by the FDA in 2015 for lowering LDL cholesterol in those with FH who need more than statins to reach their treatment goals. These drugs were developed based on the discovery of an FH gene and are now helping people with FH and many others who suffer from cardiovascular disease, reduce their risk for a heart attack.
This year, the first patient with Homozygous Familial Hypercholesterolemia (HoFH), the rare form of FH, received a dose of gene therapy as part of a clinical trial. We hold our breath, hoping that this treatment will help change the lives of people born with two FH genes, at risk for heart disease even in childhood. We celebrate the researchers who brought us to this moment, and the patients who step forward to put these advances into practice.
These advances in genomic research,represent hope for families that today’s children born with FH, and generations to come, will live longer, healthier lives, free from heart disease. Two individuals with FH share their thoughts on what advances in genomic research have meant to them:
The Mysteries of our Genomes, Translated into Action
Colleen Sweeney, PhD When I was approximately seven years old, my family was referred to Boston Children’s Hospital for evaluation of our cholesterol levels. My father, who was in his mid-forties, had just had a heart attack. This was in the early 1970s, when Brown and Goldstein were embarking upon their remarkable and fruitful collaboration, studying the biochemistry of cholesterol metabolism. This collaboration, which laid the foundation for the therapies we benefit from today, led to Brown and Goldstein receiving the Nobel Prize for Physiology or Medicine in 1985. When the cholesterol test results came back for my family, my father and I received a diagnosis of Familial Hypercholesterolemia (FH). Although as a child, I could not comprehend why my father and I were different from the rest of our family, I understood that it had something to do with the science of our bodies. Being diagnosed with FH sparked a scientific curiosity in me which has persisted my entire life. Today, I am a molecular biologist and biochemist, conducting cancer research and mentoring the next generation of scientists. As I reflect back on the scientific advances which have been made in my own and my father’s lifetime, I am filled with wonder. From the first peek at the structure of DNA in Rosalind Franklin’s “Photo 51” to the completion of the human genome project in 2003, scientific research has catapulted us into an era in which the unique details of our genomes may allow a tailored approach to therapy, in an effort known as “precision medicine”. Indeed, the discovery of mutations in the PCSK9 gene, by Catherine Boileau and colleagues, has leap-frogged the field forward, leading to a new therapeutic approach for people living with FH in the form of PCSK9 inhibitors. We are fortunate to live in this time, when the mysteries of our genomes are translated into action, improving our lives.
I Never Had a Clue
Colleen McCready I had no idea I carried a potentially fatal genetic mutation, because we never talked about our family history.
My mother was a foster child from a young age. She never spoke about her parents, probably because she didn’t know much about them. My mother was married young. My older half brother and sister were much older and I had little contact with them. It was a surprise to me to learn that my half brother had had 7 heart attacks, 2 stents, and a double bypass surgery.
I found out when I was 34 that I had extremely high cholesterol. I was looking for answers after I was diagnosed. I knew at 14 that I had high cholesterol but I had no idea where it came from or what it meant for me. I had no idea it was genetic. After a few years had passed, trying different treatments, I still had no control over my very high cholesterol. I started to want answers to my questions – Where did this come from? What exactly is this? Why aren’t the statin, the ezetimibe, and the bile acid sequestrant working on my numbers? I felt more urgency when, at age 37, I was diagnosed with Homozygous FH, the rare form of genetic high cholesterol. I was losing hope.
When the opportunity to participate in research studies came along I was ready. One study offered genetic testing. I signed up right away. I needed answers.
When I got my genetic test results, it started to make sense! It turns out that my FH is caused by a mutation that is known as “LDL receptor null” – a particularly severe mutation. So now it made sense why my numbers were treatment-resistant. With further testing I found that I have a genetic mutation that makes me statin-resistant.
Knowing my genetic mutation helps me understand how serious my disease is and that I really must pursue ALL treatment options. I will keep searching for something that will work for me.
Colleen Sweeney, PhD When I was approximately seven years old, my family was referred to Boston Children’s Hospital for evaluation of our cholesterol levels. My father, who was in his mid-forties, had just had a heart attack. This was in the early 1970s, when Brown and Goldstein were embarking upon their remarkable and fruitful collaboration, studying the biochemistry of cholesterol metabolism. This collaboration, which laid the foundation for the therapies we benefit from today, led to Brown and Goldstein receiving the Nobel Prize for Physiology or Medicine in 1985. When the cholesterol test results came back for my family, my father and I received a diagnosis of Familial Hypercholesterolemia (FH). Although as a child, I could not comprehend why my father and I were different from the rest of our family, I understood that it had something to do with the science of our bodies. Being diagnosed with FH sparked a scientific curiosity in me which has persisted my entire life. Today, I am a molecular biologist and biochemist, conducting cancer research and mentoring the next generation of scientists. As I reflect back on the scientific advances which have been made in my own and my father’s lifetime, I am filled with wonder. From the first peek at the structure of DNA in Rosalind Franklin’s “Photo 51” to the completion of the human genome project in 2003, scientific research has catapulted us into an era in which the unique details of our genomes may allow a tailored approach to therapy, in an effort known as “precision medicine”. Indeed, the discovery of mutations in the PCSK9 gene, by Catherine Boileau and colleagues, has leap-frogged the field forward, leading to a new therapeutic approach for people living with FH in the form of PCSK9 inhibitors. We are fortunate to live in this time, when the mysteries of our genomes are translated into action, improving our lives. 
Colleen McCready I had no idea I carried a potentially fatal genetic mutation, because we never talked about our family history.
My mother was a foster child from a young age. She never spoke about her parents, probably because she didn’t know much about them. My mother was married young. My older half brother and sister were much older and I had little contact with them. It was a surprise to me to learn that my half brother had had 7 heart attacks, 2 stents, and a double bypass surgery.
I found out when I was 34 that I had extremely high cholesterol. I was looking for answers after I was diagnosed. I knew at 14 that I had high cholesterol but I had no idea where it came from or what it meant for me. I had no idea it was genetic. After a few years had passed, trying different treatments, I still had no control over my very high cholesterol. I started to want answers to my questions – Where did this come from? What exactly is this? Why aren’t the statin, the ezetimibe, and the bile acid sequestrant working on my numbers? I felt more urgency when, at age 37, I was diagnosed with Homozygous FH, the rare form of genetic high cholesterol. I was losing hope.
When the opportunity to participate in research studies came along I was ready. One study offered genetic testing. I signed up right away. I needed answers.
When I got my genetic test results, it started to make sense! It turns out that my FH is caused by a mutation that is known as “LDL receptor null” – a particularly severe mutation. So now it made sense why my numbers were treatment-resistant. With further testing I found that I have a genetic mutation that makes me statin-resistant.
Knowing my genetic mutation helps me understand how serious my disease is and that I really must pursue ALL treatment options. I will keep searching for something that will work for me.
