20 years ago, we were in the gene discovery phase – even when the CCM genes were found, we didn’t know why mutations in any one of them lead to the onset of cavernous malformation. Research in the following years uncovered a complex signaling network, and we learned that these molecules are essential for proper blood vessel development and function. Now, here we are enrolling participants in multiple clinical trials and the future with a new non-surgical treatment for cavernous malformation is closer than ever before!
The road has been long, and just as long is the list of research teams, each uniquely contributing to our knowledge and leading us ever closer toward our vision of a permanent cure for CCM.
Would you like to know where research is happening and what projects are in process?
Below is a geographically organized overview of the CCM research space. The list induces a diverse summary of some of the many ongoing research projects at laboratories throughout the world.
- To learn more about current research results, read our newsletters.
- To learn about clinical research opportunities, please visit our Participate in Research page and join our Patient Registry. By signing up for the Cavernous Malformation Registry you will be notified about future studies for which you may be eligible to participate.
North America
EASTERN US
Connecticut, Massachusetts, Maryland, New York, North Carolina, Pennsylvania & Virginia
Alliance to Cure Cavernous Malformation – Alliance to Cure Cavernous Malformation’s research program includes our recruitment support, our Patient Registry, our Biobank, and a variety of natural history and genealogy studies. Our registrants support clinical research around the world with their information and their willingness to participate in studies.
Boston Children’s Hospital – Under the direction of Dr. Ed Smith, Boston Children’s was recognized as a Clinical Center of Excellence in September of 2017. Boston Children’s supports an active research program led by Dr. Moses focused on vascular diseases. Multiple projects related to CCM include work to identify biomarkers in urine that can be used for clinical screening and participation in the Brain Vascular Malformations Consortium.
Columbia University – Dr. Ghabrial is a fly researcher (the first to join CCM research!). His lab focuses on tube development (like blood vessels and breathing structures) and the regulating signals. CCM3 is involved in this complex signaling network.
Duke University – The Marchuk Lab at Duke University studies the human genetics of CCM and has developed robust mouse models of the illness. These mice are valuable tools for drug studies and are critical for translating laboratory findings to human patients. This group works in collaboration with the University of Chicago to better understand the mechanism by which lesions grow and develop. It has also described how lesions grow like a tumor when they first form.
New York University – Dr. Miao’s lab at NYU is interested in understanding better the functional properties of a cell surface molecule, the Nogo-B receptor (NgBR). His work led him to study this receptor and its roles in human disease, including cavernous malformation.
Ovid Therapeutics/Graviton Bioscience – Ovid and Graviton are in partnership to develop a ROCK2-specific inhibitor to treat CCM.
University of Pennsylvania – The Kahn lab at UPenn is interested in the signaling (molecular) pathways that regulate blood vessel growth and function. Their work with CCM mice led to the discovery that connects the gut microbiome to lesion development. Their current work focuses on the involvement of the PIK3CA protein in aggressive lesion growth. They are also collaborating on a nanoparticle drug delivery project with seed funding from the Alliance to Cure.
University of Rochester – The Glading laboratory at the University of Rochester is focused on understanding how cells interact with one another and their environment, critical components to normal cell function and signaling. Dr. Glading’s work investigates how CCM1 protein functions within these processes.
University of Virginia – The Price lab is developing and testing focused ultrasound as a treatment for CCM. The Tvrdik lab has been developing CCM1 mouse models, which may become useful in gene therapy development. They have also been exploring focused ultrasound options with the Price lab.
Yale University – Multiple labs at Yale are studying CCM from different aspects – these include analyzing the molecular structure of the CCM proteins in the Boggon Lab, as well as using mouse models in the Min/Zhou Lab to study the function of the CCM proteins in different parts of the brain and throughout the development of the blood vessel system. The Louvi Lab focuses on CCM3 biology and is investigating the efficacy of combination therapy of two approved drugs in mouse models.
MID-WEST
Illinois, Ohio, Michigan & Minnesota
Cincinnati Children’s Hospital Medical Center – Cincinnati Children’s is a recognized Alliance to Cure Cavernous Malformation Clinical Center of Excellence under the direction of Dr. Sudhakar Vadivelu, and is a site for the Brain Vascular Malformations Research Consortium. Dr. Ziyuan Guo’s lab is developing CCM organoids resembling human CCM lesions for drug screening and testing.
Mayo Clinic – Under the direction of Dr. Kelly Flemming, the Mayo Clinic in Rochester, MN earned designation as a Clinical Center of Excellence in 2017. Dr. Flemming’s research team at the Mayo Clinic is interested in understanding better the natural course of CCM disease and how lesion behavior affects patients with this illness. This group is currently studying risks associated with bleeding, seizure, and pregnancy in individuals with CCM. The Mayo Clinic is also a study site for the CASH Trial readiness and multicenter Biomarker studies.
University of Chicago – Our first recognized Clinical Center of Excellence was designated at the University of Chicago under the direction of Dr. Issam Awad. Dr. Awad’s team is interested in understanding the role of the immune response and inflammation as they relate to CCM lesion development and progression. His group has developed advanced magnetic resonance imaging (MRI) techniques to examine the effects of drug treatment on mice with CCM and to measure leakage (permeability) and iron deposits (a measure of blood leak or hemorrhage) in human patients. In the fall of 2018, Dr. Awad began enrolling participants in the first-ever clinical treatment trial for cavernous malformation hemorrhage. In the lab, Dr. Awad’s team participates in mouse treatment studies and is developing biomarkers to predict the future and measure the past course of the disease.
University of Michigan – The blood vessels of the brain are unique because they form especially tight junctions between neighboring cells to ensure that the blood they carry does not leak into the brain. This unique junction is termed the blood-brain barrier. The Andjelkovic-Zochowska lab at the University of Michigan studies how CCM3 works to maintain the blood-brain barrier.
THE WESTERN US
Arizona, California, New Mexico, Texas & Utah
Barrow Neurological Institute – BNI is a recognized Center of Excellence with Dr. Michael Lawton as its Medical Director, and it is one of the study sites for the genetic research project to investigate the causes of clinical variability between individuals with CCM. This project is part of the Brain Vascular Malformations Consortium. Also under the direction of Dr. Zabramski is a study to investigate the effect of propranolol treatment prior to surgery on the DNA and RNA activity within CCM lesions.
Neurelis – Neurelis is a biopharmaceutical company working to develop a kinase inhibitor drug, NRL-1049, for the treatment of CCM.
Recursion Pharmaceuticals – Recursion Pharmaceuticals, a drug company out of Salt Lake City, has developed a high-throughput screening platform that utilizes artificial intelligence for drug discovery in rare diseases. As of March 2022, Recursion has begun Phase II safety trials on their new drug REC-994 (tempol).
Texas Tech University El Paso – Dr. Zhang’s lab studies angiogenesis, the process of blood vessel development and branching. CCM lesions are defective in angiogenesis and Dr. Zhang’s team aims to understand better the role each of the CCM proteins has in the regulation of typical angiogenesis.
The University of California at San Francisco – UCSF was recognized as a Clinical Center of Excellence in June of 2018. Dr. Kim leads the clinical research program focused on identifying clinical outcomes and modifiers to the natural disease progression. Her research is part of the Brain Vascular Malformations Consortium and is described at length, HERE.
The University of New Mexico – UNM was recognized as an Alliance to Cure Cavernous Malformation Clinical Center of Excellence in April 2017. Dr. Michel Torbey is the medical director and runs the university research portfolio on CCM. A primary focus of his research is to identify genetic or environmental factors that modify the disease course and cause variability within and between families. This project is part of the Brain Vascular Malformations Consortium and is described at length, HERE.
University of California San Diego – The Ginsberg and Lopez-Ramirez labs study vascular biology and investigate the molecules that bind blood vessel cells to one another and how these molecules are disrupted in the disease state. This work has resulted in identifying Thrombospondin1 as a possible therapeutic target for CCM.
International Research
BRAZIL
Universidade Federal do Rio de Janeiro – Dr. Marcondes treats cavernous malformation patients, is actively involved in the Brazilian patient support organization, Cavernoma Alliance Brazil, and his research interests include studying patient-reported outcomes to determine the best course of treatment. Marcondes is a collaborator with US clinical research teams on biomarker development.
AUSTRALIA
Centenary Institute – Dr. Zheng’s research team uses zebrafish and acute mouse models to study CCM lesion development and signaling. Dr. Gamble is head of the Vascular Biology Program at Centenary Institute. Her work with microRNAs intersects with CCM biology with possible therapeutic implications.
CANADA
Samuel Lunenfeld Research Institute – The Gingras research group focuses on the protein level and investigates CCM by learning about its interacting partners. By uncovering with which other molecules the CCM proteins interact, these researchers are able to better understand the CCM proteins themselves.
Sick Kids Children’s Hospital – Both zebrafish and C.elegans (worm) models for CCM are being used here to investigate how the three genetic forms of CCM are similar to and different from one another. The Derry lab uses the power of worm genetics and rapid development to study CCM1 and CCM3 and how they are involved in tube formation, cell death, and reproductive cells. Worms are also a great tool for screening potential drugs. The Scott lab uses fish models to study cardiovascular development – CCM3 is a critical signaling molecule for cranial blood vessels.
CHINA
First Affiliated Hospital of Fujian Medical University – In a nationwide multi-site study, a Chinese team aims to enroll 2000 participants and track outcomes of those who receive surgical intervention compared to those who are following conservative management.
FRANCE
INSERM – Grenoble – Dr E. Faurobert’s research team focuses on how blood vessels interact with their surrounding environment. The team’s main interest is understanding how biochemical mechanisms and cell mechanics synergize to lead to the formation and expansion of CCMs. This team is closely collaborating with Pr Hans Van Oosterwyck’s team in KU Leuven, Belgium, to study the role of blood flow and extracellular matrix in the pathogenesis of the disease.
INSERM – Paris – Dr. Tournier-Lasserve is a medical geneticist and research group leader in developing animal models to better understand the pathogenesis and development process of the familial forms of CCM. Along with Dr. Dejana (see Italy and Sweden below), Dr. Tournier-Lasserve was awarded the Grand Prix Scientifique, a very prestigious European recognition, in 2016 for her CCM work.
GERMANY
International Neuroscience Institute, Hannover – The lab, directed by Dr. Souvik Kar in clinical collaboration with Prof. Bertalanffy, studies small non-coding RNAs and their role in vascular disease. The team has found microRNAs responsible for regulating blood vessels and related to CCM lesion development.
University of Duisburg-Essen – Among other things, the research team in Essen led by Yuan Zhu is interested in investigating the differences in the blood vessel cells comparing both sporadic and familial CCM.
University of Greifswald – The Department of Vascular Malformation is led by Dr. Ute Felbor. Her team recently developed a stable CCM3 cell line using CRISPR technology.
The University of Potsdam – The research team of Dr. Seyfried studies the signaling mechanisms that control a developing heart in zebrafish, some of which are also disrupted in CCM lesion vessels. Dr. Seyfried leads the international collaborative study that identified indirubin-3-monoxime, as a possible therapeutic for CCM and has been screening thousands of additional compounds.
ITALY
IFOM, FIRC Institute of Molecular Oncology – Dr. Dejana’s team in Milan investigates the cellular properties that make CCM blood vessels unique from other blood vessels. Identifying these unique characteristics helps to identify druggable targets. Along with Dr. Tournier-Lasserve, Dr. Dejana was awarded the Grand Prix Scientifique, a prestigious European prize, in 2016 for her CCM work.
Istituto de Ricerche – Dr. Latini led the clinical trial in Italy to research the effects of propranolol treatment on CCM patients.
The University of Torino – Dr. Retta’s group investigates the effects of reactive oxygen species and how the CCM signaling complexes neutralize these molecules.
NETHERLANDS
Amsterdam University Medical Center – Dr. Zuurbier’s team is interested in studying the effects of antithrombotic medications, like aspirin, on our cavernous malformation patient population.
SPAIN
University of Santiago de Compostela – This Spanish research team led by Dr. Juan Zalvide focuses on CCM3 and how this protein is involved in cellular proliferation and signaling complexes.
SWEDEN
Uppsala University – Dr. Dejana’s group at Uppsala studies blood vessels and how they grow to feed tumors. CCMs are not tumors, but there are shared biological pathways between the two. Dr. Dejana’s team studies the pathways responsible for the unique structural and functional characteristics of CCM lesion blood vessel cells. Her team also aims to identify drugs that may inhibit lesion formation and/or shrink lesions.
UNITED KINGDOM
Benevolent AI – With funding from the Be Brave for Life Foundation, the UK-based biotechnology company has initiated a collaboration with the University of California San Diego to marry biology with artificial intelligence. The project goal is to identify new drugs or drug targets for the treatment of cavernous malformation.
University of Edinburgh – Under the direction of Dr. Salman, this group focuses on the epidemiological aspects of CCM, questions including – how many people are affected? What are the clinical outcomes for individuals who undergo surgery compared to those who follow conservative management?
Last Updated 11.18.23
