We are making an impact by spreading awareness and helping to fund cutting-edge cerebrovascular disease and benign brain tumor research that has the potential to change current diagnostic or treatment paradigms for adult and child patients.  Remarkably, since our founding in July 2015, we have raised over $400,000.

2018: $150,000 in Micro-Grants Awarded


Angioma Alliance

The Angioma Alliance launched the first-ever patient registry for cavernous malformations in 2010 to create a communication tool to connect the patient and research communities with the goal of facilitating study recruitment. We’ve provided the funding needed for a platform upgrade to the Registry that will collect and provide standardized data directly to researchers, and to enable mobile device functionality for both participants and research partners.

There are twelve therapies currently under investigation in academic and industry labs [for CCM treatment]. As clinical trials progress, this upgrade will ensure that the patient community is ready and available to contribute to finding better treatments.

 

— Amy Akers, PhD, Angioma Alliance Chief Scientific Officer

Boston Children’s Hospital, Katie Pricola Fehnel, MD

This research project is designed to identify the key components that differentiate benign brain tumors from other cancers so that benign lesions can be better targeted. This grant will serve as a stepping stone to NIH funding.

Centenary Institute, University of Sydney, Australia

Despite recent advances, we still lack any targeted therapeutics to prevent or stabilize CCM lesions. This project, to determine if Adamts (a secreted, extracellular metalloproteinase) deletion can prevent CCM lesion formation, has great potential to set foundations to identify a new drug treatment for CCM patients where currently there are none.

Collaboration: Our recent work published in Nature in 2017 involving 15 different research groups from Australia, China, Europe and USA demonstrate for the very first time the link between stroke and gut microbiome. This work has attracted huge interest and attention around the globe as evidenced by numerous media articles including the New York Times.

— Jaesung P. Choi, MD and Xiangjian Zheng, MD

Collaboration between Mirrx Therapeutics, Centenary Institute, University of Chicago and Axolabs

This group has developed a Blockmir CD5-2 that may be used to treat CCM.  This funding will provide for patient tissues and matched normal tissues to be investigated.  This group has substantial data showing they can reduce existing lesions in both size and number.

To our knowledge this is the first compound able to not only prevent lesions from forming, but which can also reduce and possibly even entirely remove already existing lesions. […] We have substantial data showing that we can reduce existing lesions in both size and number in Cerebral Cavernous Malformation when we treat mice bearing CCM2 mutations with CD5-2. Our goal is to bring CD5-2 to the market as a novel treatment for CCM.

 

— Christina Udesen, PhD, Chief Scientific Officer, Mirrx Therapeutics

IFOM, the FIRC Institute of Molecular Oncology, Milan, Italy

The project, The Vessel-Associated Endothelial Progenitor Cells: a new paradigm for cerebral cavernous malformations origin, is a concept study for the identification of a new mechanism for the pathogenesis of CCMs, through which cavernomas would be considered, and likely treated, as benign tumors of the endothelium.

This project has the potential of creating a pioneer and innovative approach to identify new and specific pharmacological therapies to treat this disease.

 

—  Matteo Malinverno, senior post doc in Vascular Biology Unit

University of California – San Francisco Medical Center

The research pilot project evaluates circulating (blood) micro RNA as a potential biomarker of disease severity and progression in familial cerebral cavernous malformations, which may signal a need for treatment and guide clinical management of patients. Both negative and positive results from this pilot study will be informative and provide strong preliminary data necessary for a larger NIH grant proposal planned for submission in late 2018.

The impact of [this] study is two-fold. First, understanding of what determines CCM disease severity and rate of progression is lacking. Identification of biomarkers of disease severity will aid in mechanistic understanding of the disease, and in the development of more accurate disease prognosis and medical management…Second, there is a significant unmet need for medical therapies of CCM. Clinical trials of any novel or existing therapies require biomarkers to assess outcomes and monitor progression.

 

— Ludmila Pawlikowska, Ph. D

University of Chicago

Pilot funding for an independent sample validation of prognostic plasma biomarkers predicting CCM symptomatic hemorrhage or lesion growth provides gap support to leverage a much bigger investment by the National Institute of Health (NIH).

In pilot studies, we asked for the first time, the “million dollar” question, whether levels of the mechanistically relevant biomarkers in peripheral blood plasma can predict symptomatic hemorrhage or lesion growth in the subsequent year. This would be the holy grail of ultimate biomarker performance, a blood test that tells patients whether their lesion would grow or bleed, or not, in the near future. Our pilot results were recently presented at the International Stroke Conference in January 2018, and were nothing short of breathtaking.

 

— Issam A. Awad, MD, MSc, FACS, MA (Hon), University of Chicago Medicine and Biological Sciences

Bridge funding for the construction of VISION, the electronic data capture (EDC) system, a CCM-specific research database for trial readiness that focuses first on cavernous angiomas with symptomatic hemorrhage (CASH). CASH are the cases most likely to rebleed, experience cumulative disability, and disruptions in quality of life (QOL), and are most likely to enroll in clinical trials of novel agents.

We propose for the first time a harmonized multisite assessment of enrollment rates of CASH, determination of baseline features relevant to stratification in clinical trials, and follow-up assessments of functional outcomes and QOL in relation to clinical bleeds…The recent James Lind Alliance priority setting partnership conducted by Cavernoma Alliance U.K. identified among the top priorities for research several aims of this trial readiness proposal. Such a project has never been undertaken in a benign brain disease, and CCM will serve as a model in this regard.

 

— Issam A. Awad, MD, MSc, FACS, MA (Hon), University of Chicago Medicine and Biological Sciences

University of Pennsylvania, PennCHOP

This is a translational research project investigating the effects of the gut microbiome on cerebral cavernous malformation (CCM) disease in human patients. The goal of this project is to determine whether variations in the gut microbiome are associated with CCM disease severity.

The completion of this project will potentially validate a therapeutic approach to change the standard of care for hundreds of thousands of patients affected by CCM disease…Any findings may be broadly applicable to other neurovascular malformations.

 

— Dr. Mark Kahn, Professor of Medicine, UPenn

 

2016-2017: More Than $200,000 in Support


Boston Children’s Hospital (BCH)

We’ve provided over $100,000 to support Dr. Edward Smith’s laboratory efforts that focus on developing new tools to diagnose and treat diseases that cause tumors and strokes in children. Funded in part by the Be Brave For Life Foundation, Dr. Smith’s lab recently discovered that certain molecules—urinary biomarkers—when found in the urine, indicate the presence and progression of brain tumors and vascular diseases (such as AVMs and CCMs).

Dr. Smith has a particular interest in brain tumors, cerebral cavernous malformations (CCMs), arteriovenous malformations (AVMs) and moyamoya, as these are the conditions that most often affect the children he sees in his practice. Over the past few years, Dr. Smith and his team have developed specific biomarker panels that identify different types of disease. To date, his lab has developed unique diagnostic “signatures” for medulloblastoma, glioma, glioblastoma, juvenile pilocytic astrocytoma, AVMs, moyamoya disease, and Chiari malformations. These “signatures” enable increased diagnostic accuracy using non-invasive urine testing since, as Dr. Smith points out, “nobody likes needles, especially kids.”

Urine testing has unique advantages, in that collecting urine is non-invasive (no needles), does not require general anesthesia, sedation or radiation (like MRI or CT) and can be done at home (saving trips to the medical centers for imaging). In addition, urine tests are 10-100 times cheaper than MRIs, allowing for more frequent testing and savings for everyone involved. Most importantly, the use of urine testing for specific molecular fingerprints means that there is now a new way to test for the disease. The discovery of these molecular fingerprints can help identify new targets for treatment, in addition to improving diagnostic accuracy.

To be clear, researchers do not anticipate using urine tests to replace MRI or CT, but they hope that the development of this new technology will complement existing tools to make the identification and treatment of these challenging diseases more effective than ever before.

What is so special about what Be Brave For Life is helping to fund is that cerebrovascular diseases are often conditions that other bigger funding groups generally don’t want to touch.

 

— Edward Smith, MD

Barrow Neurological Institute (BNI)

Be Brave For Life has also provided $115,000 to support Joseph Zabramski, MD, and his team’s research into a new treatment for cerebral cavernous malformations (CCMs). While four decades of research into CCMs has resulted in a greater understanding of the growth of these lesions, treatment options remain limited. Physicians can manage a patient’s symptoms or remove the CCM(s), but not without potentially adverse neurological effects or life-threatening risks. Barrow neurosurgeons and researchers are working to change this by testing an oral drug that is believed to shrink and possibly eradicate CCMs, thus avoiding invasive surgery and improving outcomes.

This has been an exciting year for Dr. Zabramski and his research partners, Barrow’s Robert Spetzler, MD, Translational Genomics Research Institute’s Matthew Huentelman, Ph.D., and University of Utah’s Yashar Kalani MD, Ph.D. A number of clinical trials have demonstrated that propranolol (a low-cost and FDA-approved medication with a long history of widespread clinical use) can significantly shrink cutaneous hemangiomas in infants and that the drug is extremely safe in this population. Because of the similarities between cutaneous hemangiomas and CCMs, they have proposed that propranolol may be an ideal candidate for treating both types of lesions.

Based on initial positive research results using oral propranolol, published in the April 2016 issue of World Neurosurgery, and with financial support of Be Brave For Life, Dr. Zabramski and his team have continued investigating the use of oral propranolol in a small number of patients at Barrow who are unwilling or unable to consider surgical intervention.

Recently, the team presented a proposal for a Phase III clinical trial of oral propranolol at the12th Annual Scientific Meeting of the Angioma Alliance on November 10th, 2016 in Washington, D.C. The presentation entitled, “A Proposed Trial of Oral Propranolol for Symptomatic Cerebral Cavernous Malformations not Amenable to Surgical Resection,” was well received, and there is now international interest in this clinical trial. Following the meeting, Drs. Zabramski and Kalani met with the program director of the National Institute of Neurological Disorders and Stroke and National Institutes of Health, Jim Koenig Ph.D., to discuss government funding for their study. The team is also working with several groups in Italy to submit a joint funding request to the National Institutes of Health later this year

Further, Dr. Zabramski’s team recently completed necessary preparation and design for a clinical research protocol at Barrow which promises to provide insight into the mechanism of propranolol’s effect on CCMs. The research team expects to complete participant enrollment by summer of 2017. Knowledge regarding the potential mechanisms of propranolol’s effect on CCMs is essential to obtaining government funding for a Phase III clinical trial.