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Current Research Projects

Are you curious about cavernous angioma (cavernous malformation, CCM, cavernoma) research?

15 years ago, we were in the gene discovery phase and then when the CCM genes were found, we still didn’t know what they did and why mutations in any one of them lead to onset of cavernous angioma. Now, here we are enrolling participants in two clinical trials!

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 prospering 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.

 

North America

EASTERN US

Connecticut, Massachusetts, Maryland, New York, North Carolina, Pennsylvania & Virginia

Angioma Alliance - Angioma Alliance’s research program includes our CCM DNA & Tissue BioBank and Brain Vascular Malformation Consortium (BVMC). The biobank program collects biological samples (surgical tissue and blood) and medical records from CCM patients and provides these important resources to our researchers. To learn more, please visit: www.angioma.org/dna The goal of the BVMC study is to understand better the genetic factors that influence disease severity. 

BioAxone BioSciences, Inc. – BioAxone is a biopharmaceutical company working to develop a kinase inhibitor drug, BA-1049, for the treatment of CCM.

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. One project related to CCM aims to identify biomarkers in urine that can be used for clinical screening.

Columbia UniversityDr. 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 understand better the mechanism by which lesions grow and develop and has also described how lesions grow like a tumor when they first form.

Hampton University – Researchers at Hampton use zebrafish to study cardiovascular development. It was this team that discovered the CCM1 and CCM2 genes in fish. In fish, these genes are called santa and valentine

National Institutes of Health – The Weinstein lab at NIH focuses on studying blood vessel systems using a zebrafish model. Zebrafish are an excellent tool when studying the effects of genetic mutations in the vasculature – their developing bodies are transparent, making them perfect for fluorescent microscopy. 

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 connecting the gut microbiome to lesion development. 

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.  

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 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 recently discovered that a combination therapy of two approved drugs is effective in treating mice with CCM. 

 

Mid-West

Illinois, Ohio, Michigan & Minnesota

Cincinnati Children’s Hospital Medical Center – Cincinnati Children’s is a recognized Angioma Alliance Clinical Center of Excellence. Under the direction of Dr. Sudhakar Vadivelu, the research program focuses on brain blood vessel development and associated signaling mechanisms. 

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. 

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 angioma hemorrhage.  

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. 

 

WESTERN US

Arizona, California, New Mexico, Texas & Utah

Barrow Neurological Institute - BNI has teamed up with UNM, UCSF, and Angioma Alliance to run a genetic research project to investigate the causes of clinical variability between individuals with CCM. This project is part of the Brain Vascular Malformations Consortium and is described at length, HERE. 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. 

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 November 2018, Recursion has begun Phase I safety trials on their new drug REC-994 (tempol). 

Texas Tech University El PasoDr. 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 Angioma Alliance Clinical Center of Excellence in April 2017. Dr. Zafar 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 investigating the molecules the 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.  

The University of Utah - The research group at the University of Utah uses multiple systems, including mice, to investigate the molecular cause of leak from CCM lesions. This group was the first to discover that statin drugs may have a future use as a CCM treatment.

 

International Research

BRAZIL

Universidade federal do Rio de JaneroDr. Marcondes treats cavernous angioma 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.

 

AUSTRALIA

Centenary InstituteDr. 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.  


DENMARK

Ranger BiotechnologiesRanger Biotechnologies is a drug company aimed at developing therapeutic products from short lengths of nucleotides (the building blocks of DNA). Their products are called Blockmirs. One Blockmir, CD5-2, targets blood vessels and is under investigation for the treatment of CCM and other illnesses. 

 

FRANCE

INSERM – Grenoble - This French research team focuses its research on how blood vessels interact with extracellular matrix (surrounding tissue) to provide structure as wells as signals that are essential for proper growth, development, and directionality. 

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. Most recently her animal models were used in the discovery that indirubin-3-monoxime, may be therapeutic for CCM. Along with Dr. Dejana (see Italy and Sweden below), Dr. Tournier-Lasserve was awarded the Grand Prix Scientifique, very prestigious European recognition, in 2016 for her CCM work. 

GERMANY

International Neuroscience Institute, Hannover – The lab directed by Dr. Bertalanffy studies small non-coding RNAs and their role in vascular disease. The team has found microRNAs that are responsible for regulating blood vessels and are 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 vessels 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. 

 

ITALY

IFOM, FIRC Institute of Molecular Oncology – Dr. Dejana’s team in Milan investigates the cellular properties that make CCM blood vessel 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. Lantini is leading a 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 are involved in neutralizing these molecules.

 

SPAIN

University of Santiago de Compostela - This Spanish research team led by Dr. Juan Zalvide focuses its studies on CCM3 and how this protein is involved in cellular proliferation and signaling complexes.

 

SWEDEN

Uppsala University – Dr. Dejana’s group at Upsalla 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

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 under surgery compared to those who follow conservative management?  

 

 

 

 

 Last Updated 1.20.19