By Douglas Marchuk, Chair, Alliance to Cure Cavernous Malformation Scientific Advisory Board
The National Institutes of Health (NIH) occasionally provides funding for a team of researchers, often from different institutions, to work together to perform research that could not be accomplished in a single laboratory. With each laboratory bringing their unique expertise to the project, the goal is to create a team that can make progress towards understanding disease. These grants are called Program Project Grants (PPGs). Some years ago, Drs. Douglas Marchuk (Duke University), Issam Awad (University of Chicago), Mark Ginsberg (University of California at San Diego), and Mark Kahn (University of Pennsylvania) wrote an NIH PPG proposal for cavernous malformation (CCM) that was funded for 5 years, and which was competitively renewed for another 5 years.
Over the years our research team has made seminal discoveries on CCM pathogenesis, some of which are leading to new approaches to treatment. Some examples include
- the importance of Rho kinase signaling in CCM disease (which has led to the current clinical trials of statins for CCM disease),
- the role of the gut microbiome in promoting CCM growth (leading to further studies on gut health in CCM disease),
- the role of somatic mutations in CCM disease, in particular in the gene for the signaling protein PI3 kinase, (which is currently leading to novel approaches for CCM therapy including the use of rapamycin),
- the role of another signaling protein (beta-adrenergic receptors) in CCM disease (leading to clinical trials of propranolol and other beta-adrenergic receptor antagonists for CCM therapy),
- and the role of hypoxia (low oxygen levels) in the development of CCMs (leading to studies to determine if sleep apnea plays a role in CCM disease).
These are just some of the important discoveries made by our team that are leading to new avenues for CCM therapy. Recently, our team’s NIH Program Officer (Dr. James Koenig, who recently retired from NIH) told us that our PPG was one of the most successful grants he had seen in his decades-long career as an NIH official.
Another important metric of success of an NIH PPG is to train the next generation of scientists, with the hope that they will continue research on the disease under study. In this endeavor, our PPG was also very successful, with literally dozens of graduate students and postdoctoral fellows across all four institutions who worked on these collaborative studies and have gone on to the next stages in their careers. In particular, through this award, Dr. Miguel Lopez Ramirez (UC San Diego) furthered his training and was recently awarded his own NIH grant on CCM pathobiology, with an emphasis on the role of hypoxia (low oxygen levels) and neuroinflammation in CCM pathology.
We are grateful to the NIH for the funding to carry out this work, and especially to the Alliance to Cure Cavernous Malformations for their continued support of our research team. Unfortunately, our NIH PPG award ends on May 31, 2025. NIH PPG awards are only renewable once, so our collaborative team that has worked together so successfully for the past decade cannot reapply again for funding. Individually, each of us has written NIH grant proposals on CCM that we hope will be funded in the future. However, there is some concern about the future of NIH-funded research.
Although for many decades the NIH has enjoyed bipartisan support of their mission to improve the health of our nation, the NIH is now under onslaught. We encourage all of you to contact your congressional representatives and ask them to continue to support the mission of NIH, especially with continued support for research on CCM.
This article was featured in our Spring 2025 Newsletter, published in March 2025.
