Elle’s Angels Atlanta raised $110,000 at our inaugural event in 2022, where Angioma Alliance founder, Dr. Connie Lee, addressed our guests. Changing their name to Alliance to Cure, our donation to ATC funded their first ever research grant to UVA to support their work in developing non-invasive treatment for CCM tumors. If the mouse trials being funded by this grant are successful, UVA will be able to apply for expanded funding from the NIH. More on this and other research initiated by Alliance to Cure follows.
Targeted Drug Delivery Using Nanoparticles:
In 2023, the Alliance to Cure is funding targeted delivery research using nanoparticles. This exploration of advanced drug delivery methods will potentially allow treatment medications a direct path to targeted tumors. This work goes hand-in-hand with the recent discovery of the cancer-like biology of CCM. But resorting to cancer drugs to shrink CCM tumors is riddled with side-effects. This science allows technicians to isolate the tumor for direct delivery of the treatment drug, lessening the impact of side-effects. Targeted drug delivery research and implementation are already well underway in other diseases. An announcement about this research funding will be made by June 2023.
The grant Alliance to Cure awarded University of Virginia funds research using focused ultrasound (FUS) and sonosensitizers as a treatment for CCM. FUS is a non-invasive technique in which a focused beam of ultrasound targets a lesion. The skull is not opened and there is no radiation involved. 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 in combination with a substance that becomes caustic when it’s exposed to focused ultrasound (sonodynamic therapy). As of this writing, FUS has been used to treat approximately 2000 patients with brain disorders, primarily for brain tumors. It is not yet in human trials for CCM, but initial work is being conducted in cultured human cells and CCM mouse models at UVA.
This repurposed medication is in Phase 2 of the trial and is now fully enrolled. Patients will remain in the study for two years to determine viability of the drug in stabilizing CCM’s. The trial is under the direction of the CCM’s medical authority, Dr. Issam Awad, and being conducted at University of Chicago where Dr. Awad is Director of Clinical Neurosurgery.
Recursion is a clinical-stage biopharma company with 300+ scientists who map and navigate biology designed to bring better medicines to patients in faster and better-tolerated ways. REC-994 is in Phase 2, following animal trials where the CCM group saw a reversal of cell rupture and a decrease in the number of tumors. The medicine being tested is the first medicine created specifically for CCM patients and promises to improve the integrity of brain-cell walls, so they are normalized, and healthy vasculature is restored. There are 11 test sites nationwide, including Stanford, UPenn, UCLA, UVA and Columbia…expanding to both Emory & UF in 2023.
Thirteen labs worldwide have joined a consortium to build a database of mouse models. Their findings are already directing funding, as well as a multi-institutional research plan. Also planned is a multi-national trial which will allow multiple treatments to be tested at once. The trials share a placebo arm. The structure of these trials is called platform trials, requiring international institutions and industry partners to collaborate in new ways.
The Alliance to Cure has awarded grant support to the University of Rochester for gene therapy work being done specifically for CCM patients. Treatment for cerebral cavernous malformation (CCM) is currently limited to surgery. While new drug therapies in development offer hope for disease management, they do not represent a cure. Combination therapy is promising, but comes with significant side effects, and is not suitable for use in children. University of Rochester’s studies in gene therapy aim to develop novel tools that could be used to rectify the mutations that underlie CCM development in patients of any age. Alliance to Cure’s efforts to fund gene therapy that aims to directly target brain endothelial cells could offer patients hope for safe treatment.
Lescol & Reclast Combined Therapy:
In a high-throughput screen of FDA-approved drugs and a CCM cellular model, Yale researchers identified a combined treatment with fluvastatin and zoledronate as a potential CCM treatment. In models of CCM3 deficient mice, the combined therapy is able to significantly prevent the development of CCM tumors and extend the lifespan of the CCM3 animals. These medications are currently used to treat multiple myeloma, cancer, hypercalcemia, and osteoporosis.