PVDOMICS and What It Means for the PH Community

Since 2000, PHA has created five distinct research programs through which we have committed almost $16,000,000. Each year, through those programs, we support about a dozen research projects. Each year, through our partnerships, our donors' research dollars are doubled.  

PHA's most recent research partnership - our second with NIH - will help expand a new program that is generating more excitement among researchers than anything we've seen before. PHA's $500,000 commitment, while adding 2 percent to the overall budget, is allowing the program to expand by 20 percent. We feel that's a great investment!

This week, I'm pleased to introduce PHA's Senior Director of Medical Services, Michael Gray, as our guest blogger. He explains the new PVDOMICS program and what it means to the PH community.  

As I turn this page over to Michael, I should tell you that PH is the first disease that will be studied in this way. NIH has told us we are preceding the diseases that will follow because of the strength and structure of the PH community. As part of this community, you are making this important advance possible.

"The only simple truth is that there is nothing simple in this complex universe. Everything relates. Everything connects"
-Johnny Rich, The Human Script

For centuries, scientists have been fascinated with how traits are passed from one generation to another. Significant progress has been made in this understanding, from Gregor Mendel’s discovery of the laws of inheritance with pea plants in the mid-nineteenth century to Dr. Marshall Nirenberg decoding the language of DNA at the National Institutes of Health (NIH) in the mid-twentieth century. Despite our increased understanding, we still have not solved how genes and changes to your genetic code called “mutations” affect most diseases, including pulmonary hypertension. A new initiative through the NIH, the “Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics” (PVDOMICS) program, seeks to change that for this particularly devastating disease state.

Mutations, or accidental changes in the DNA code, can occur frequently as cells duplicate, and can even be passed onto the next generation when this mutation occurs in a sperm or egg cell. Mutations sometimes will cause no changes to the individual, sometimes will cause harm to the individual, and sometimes can even provide a benefit. Genetic changes like this have been directly implicated in a number of diseases, including cystic fibrosis, sickle cell anemia, Tay-Sachs disease, and phenylketonuria. Genetic changes have also been implicated in PH, most famously with the discovery of the “bone morphogenetic protein receptor, type II” (BMPR2) gene. However, we don’t know exactly how changes in the BMPR2 “code” lead to PH. We know that BMPR2 genetic mutations are present in more than 70 percent of people with hereditary PAH and 25 percent of people with idiopathic PAH; but having the genetic mutation does not mean you eventually have PAH.

Think of DNA like letters in a book. Individually, these letters have no meaning; together, they tell the story that makes you, you. This story can be changed in a number of ways. Certainly letters and even entire words can be added, removed or changed, which might or might not change the meaning of the story. But direct changes to the letters on the page is only one modification that can have an impact on how you read the story. Maybe your book has a sentence that has been highlighted, or bolded; the words and the meaning of this sentence have not actually changed with this modification, but it has been emphasized in a way that has consequences in context. Maybe your book has a stain on one of the pages masking several words; the words are still there, but hiding these words could change the entire meaning. These different types of changes to how the “story” of your DNA is told make up a web of interactions that can have consequences nearly as drastic as finding one disease causing “gene.” This web includes the molecules that take chapters of your DNA “story” from the nucleus to your entire cell (called RNA), the proteins that are made by this RNA and used by your entire body, and how your cell uses energy to name just three strands of this web.

The NIH in Bethesda, Md., is the world’s largest biomedical research institute, with more than 5,000 scientists working on a number of scientific advancements with basic scientists, physician scientists, patient advocacy organizations, pharmaceutical companies and, of course, patients and family members themselves. The NIH has a long history working in pulmonary hypertension, beginning more than 35 years ago with an early, important registry characterizing the devastating nature of PAH. Since then—with significant advances in the field including 12 PAH-targeted therapies, a successful surgical therapy for CTEPH, and a medical therapy for a specific form of CTEPH—the NIH continues to invest in successful PH research. The most recent demonstration of this is the PVDOMICS program.

PVDOMICS seeks to ask research questions about PH in a way that will lead to a better, more complete understanding of the disease and to developing therapeutics that are more precise by building a clinical research network of seven centers across the United States. They will be performing a comprehensive analysis on around 1,500 patients with all types of PH (WHO Groups 1-5), collecting a range of clinical information; blood for analysis of genetics and the molecules that turn on and off expression of these genes; and imaging studies normally used in the clinic to better understand the difference between normal and diseased lung vascular tissue. There are many benefits from analyzing these very different types of information together, according to the NIH. If the investigators are able to develop this robust, more complete understanding of why some people develop PH and others with similar risk factors do not, more sensitive measures of diagnosis, more uniform responses to medications, and new biomarkers of disease worsening could be discovered. It is anticipated that most WHO Group 1-5 pulmonary hypertension patients who want to participate in this research study may be able to enroll.

The Pulmonary Hypertension Association is a proud partner with the NIH in this important study, and in 2014 awarded a five-year grant of $500,000 to the program to support one of the clinical centers in collecting data from 250-300 patients. For more information on the PVDOMICS program, please see the Pathlight article on PVDOMICS from the winter 2015 issue.

Research...

I talk a lot about PHA's four distinct research programs and the partnerships we have developed.  PHA is proud that in this small disease over a million dollars in research funding is provided through them each year.

What I don't talk a lot about is how much additional PH research funding is generated through our advocacy work.

Dr. Lisa Taylor's work is a great example. 

In 2005,  PHA began to look at the Department of Defense (DOD) medical research program.  Gavin Lindberg, who does a lot of our Capitol Hill work, began to collect letters from PH patients and family members in the military, explaining the importance of PH research to them.  (That's Gavin on the left, receiving an award from PHA's then Board Chair, Carl Hicks, a retired army Special Forces colonel.) In 2006, PH was listed for the first time as a disease eleigible for DOD research funding.

Today, Gavin wrote to let us know about Dr. Lisa Palmer at the University of Virginia who has received a grant for $946,875.00 to study aspects of pulmonary arterial hypertension. Read about her grant.

Advocacy can't do the reasearch.  It can't guarantee the creation of excellent research projects.  However, in a growing field with bright researchers, we can and do open doors and make new opportunities available.

Like our internal reseaearch programs, that's something to be very proud of, too!

still too often...

In the  last issue of Pathlight, our Board Chair, Carl Hicks, wrote about his visit with Sharon Wilson and her family. We got word yesterday of her passing.  We mourn with her family.  We mourn for her and for all the good people we continue to lose to this terrible disease.  They drive us forward fo the day when we can truly say, "no more".

Here is a reprint of Carl's article.

Those of you who have heard me speak have heard me sometimes refer to this journey we are on as the “Trail of Tears.” I am quick to point out that along this route all of us seem to experience both tears of sadness as well as tears of joy. Yesterday I spent some time with a remarkable family I met on the trail. Both kinds of tears flowed for better than an hour.


Sharon and David Wilson, of Bellevue, Wash., live in a modest home with their sons Michael and Matt. A typical all-American family on the surface, David is now retired. Sharon has given up a promising career and a life of service as a teacher just prior to attaining her lifelong goal of a principal’s position. What makes this couple different is that David, a non-smoker, is stricken with lung cancer, while Sharon is now completely bedridden with pulmonary hypertension. And, the day prior to my visit, Sharon had just written a check for $200,000 to PHA. Through her generous donation to PHA, Sharon has accomplished her dream of helping others within her own lifetime.


As we all visited in Sharon’s bedroom, I ached inside for what surrounded me. Then Sharon would smile a really pretty smile and tell me how much she had enjoyed her chosen work of teaching and mentoring the kids in her classes. She has been able to give something to her school, and we cried tears of happiness together. The unfairness of what had struck their family and the inevitable “Why me?” question led to more tears of sadness. We all had a chuckle when I had to ask Michael, the youngest of the two boys, his age after hearing him recount several years of service in the Navy. “He’s just a babyface” the rest of the family chimed in unison as if they’d answered that question dozens of times. I shed a few tears of happiness at the closeness of this family because I knew they would need it to help each other out. I did my very best to thank Sharon and her family on behalf of all of us for her selfless act of kindness with her magnificent gift. As I tried to explain how her dollars, designated for research, would someday help to alleviate the suffering for untold numbers of people of all ages stricken with this illness, we cried more tears of both joy for those she would help save and sadness for those she couldn’t.

Leaving, I tried to get a promise from her that she wouldn’t go anywhere prior to our celebrating her birthday on September 26. She smiled again, a beautiful smile of peace that suggested now, especially after the tremendously kind acts of the past few days, her work here was nearly done. The tears came again for me as I pondered that, hugged her goodbye and headed for home.


The “Sharon Wilson Pulmonary Hypertension Research Fund” has been constituted at PHA. Every penny of Sharon’s contribution will go to research for the cure.