Based on our inside knowledge of the CCM field and our understanding of the greater research landscape, the Alliance to Cure Cavernous Malformation identifies high-impact, generally high-risk/high-reward opportunities for funding. We search for potential research partners, focusing our outreach on programs with the best potential to move the work forward. Once we have selected a partner and they have accepted, we collaborate on the research plan and budget. At this time, we do not accept unsolicited grant applications.
Currently Funded Projects
Focused Ultrasound
The Alliance to Cure Cavernous Malformation has awarded $87,000 to the laboratory of Dr. Petr Tvrdik at the University of Virginia to fund research using focused ultrasound and sonosensitizers as a treatment for CCM. Focused ultrasound has several mechanisms of action. Like laser surgery, it can work through ablation by heating and destroying tissue. It can also be used with a substance that becomes caustic when exposed to focused ultrasound. This is called sonodynamic therapy and requires a minimal increase in temperature. The initial work is being conducted in cultured human cells and mouse models of CCM.
Gene Therapy
The Alliance to Cure has awarded $18,400 to Dr. Angela Glading at the University of Rochester to support her work developing gene therapies for CCM.
Treatment for cerebral cavernous malformation (CCM) is currently limited to surgery, though several drugs are in pre-clinical development or clinical trials. While these new therapies give hope that we will one day be able to manage the disease, they do not represent a cure. Pre-clinical studies of the drugs currently in development have, at best, demonstrated a 50% reduction in lesion burden. Combination therapy (treatment with more than one drug at once) could be more effective, but this type of therapy is likely to have significant side effects, which may limit how long the drugs can be used and their use in children. These limitations have led Dr. Glading’s lab to look at gene therapy as a treatment/cure for CCM. This project aims to develop novel tools that could be used to rectify the mutations that underlie CCM development in patients of any age.
This grant will fund efforts to target gene therapy to brain endothelial cells directly rather than to every cell in the body. This would make gene therapy, once it’s developed, a safer option for our patients. Our funding will cover a small but critical portion of this work, synthesizing AAV particle production.
2023 Upcoming projects
CD5-2
In 2020, the Gamble lab at the University of Sydney’s Centenary Institute published Targeting miR-27a/VE-cadherin interactions rescues cerebral cavernous malformations in mice in which they explored the use of CD5-2, a target site blocker [TSB]) that prevents the mRNA interaction of miR-27a/VE-cadherin in mice bred with CCM mutations. From their abstract:
In a neonatal mouse model of CCM disease, CD5-2 normalizes vasculature and reduces vascular leakage in the lesions, inhibits the development of large lesions, and significantly reduces the size of established lesions in the hindbrain.
There were two limitations to this experiment – the mice used in the experiment were very young and didn’t have established lesions when the treatment began. Additionally, individual lesions were not monitored over time. This is because Centenary did not have mouse models that survived into adulthood and did not have the technology for mouse MRI. In 2023, the Alliance to Cure Cavernous Malformation is funding the next step in this research – testing CD5-2 in adult mice with established lesions and following the development (or regression) of these lesions over time using MRI. To our knowledge, this is the first time sequential MRI will be used to see treatment effects in a mouse model. An announcement about this research funding will be made by March 2023.
Targeted Drug Delivery Using Nanoparticles
With your help, we will fund the exploration of advanced drug delivery methods to get treatments directly to lesions. This work goes hand-in-hand with the recent discovery of the cancer-like biology of CCM. If we need to resort to cancer drugs to shrink a lesion, we want to isolate the drugs’ activity to the lesion itself to prevent side effects. Targeted drug delivery research and implementation are already well underway in other diseases. It’s time for us to figure out how to make it work for CCM. In 2023, the Alliance to Cure Cavernous Malformation will fund targeted delivery research using nanoparticles. An announcement about this research funding will be made by June 2023.
Updated 2/12/2023
