With the success of Roland Thoms’ 9th Annual Halloween Bash in 2013 – an annual event that takes place in North and South California, proceeds raised went to five different NF2 research projects this year.
The projects supported this year are:
A new Children’s Tumor Foundation (CTF.org) program designed to accelerate treatments for NF2. This is a first-of-its-kind NF2 research collaboration. This unique consortium brings together a multidisciplinary team of scientists from 7 world-class academic and medical centers of excellence, who have pledged to work closely together – sharing information, datasets, results – in real time, with the goal of speeding up the drug discovery process.
This group of researchers come to this project with a variety of backgrounds, from basic science to translational science to clinicians who will collaborate in real time, sharing successes and failures to avoid redundancy and save time and resources.
Advocure has funded $25,000 of the first year of the project, and will collaborate with CTF as needed. CTF is committed to funding $3 million in Synodos in the next three years. They are currently looking for additional funders interested in this transformative project.
Dr. Chang had been studying natural compounds as a treatment alternative for NF2 tumors. During this time, he found silvestrol to be most efficacious in shrinking tumors.
Dr. Chang’s proposed study is to evaluate silvestrol and its related rocaglates, which target multiple converging oncogenic signals through translation inhibition, as potential therapies in NF2 schwannomas. Specifically, Dr. Chang’s group plans to compare how silvestrol, a potent anti-neoplastic natural compound from tropical Asian plant Aglaia foveolata, suppresses the growth of NF2-deficient schwannoma and normal Schwann cells and investigate its mechanism of action.
Also, they have identified several silvestrol-related rocaglates that possess potent growth inhibitory activities similar to silvestrol but have chemical structures simpler (and smaller in molecular weight) than silvestrol. Therefore, these compounds will be easier to synthesize for clinical use.
They plan to evaluate the anti-tumor activities of these silvestrol-related rocaglates in animal models for NF2-related tumors. Their ultimate goal is to develop an effective medical therapy that could significantly improve clinical care and long-term treatment outcomes for patients afflicted by NF2.
Dr. Chang had previously worked in collaboration with Dr. Welling and his study using Naturals to treat NF2, which was partially funded by Advocure. Dr Chang will be taking over the study as Dr. Welling has recently transferred to MGH (Massachusetts General hospital).
Dr. Yi’s research will be to test the feasibility of establishing human schwannoma cell culture using Cellular Reprogramming technology. There is a critical need for this technology in NF2 as cells mutate and no longer reflect the original tumor that was surgically removed. If the cells from a tumor can be maintained in their original form, i.e., not mutate, testing of drugs on these tumors will be possible for personalized medicine for that individual’s specific tumor, thus increasing the chances of a positive response.
Two primary newly resected human schwannomas and adjacent normal nerve tissues will be subjected to culturing with various conditions according to Cellular Reprogramming technology. Once the cell lines are established, they will be stained with various markers to confirm their Schwann cell origin. The established lines will then be subjected to drug screening to identify drugs that preferentially inhibit the growth of schwannomas cells versus the normal Schwann cells.
NF2 Drug Discovery: Repurposing FDA Approved and Late Phase Clinical Trial Drugs for NF2 Therapeutics
Dr. Fernandez-Vallue will conduct a small scale in vivo mouse testing study for one to two drugs using an orthotopic nerve graft model. They will use a nerve graft mouse model, which takes 2-4 months to evaluate a drug rather than the 6-12 months it takes to evaluate drugs in a genetic NF2 mouse model. This model has recently been used and validated in other labs. They will then treat the mice with the drugs and test their ability to stop tumor growth or to shrink them.
NF2 State of the Art, MGH
This annual conference brings together international researchers in translational and clinical science to assess current knowledge and identify opportunities for improving treatment of NF2. The 2014 meeting will focus on areas of controversy in NF2 to stimulate productive conversation among experts within the field. Areas of focus include surgical, chemotherapeutic, and radiation treatment, as well as quality of life, mechanisms of hearing loss, and the use of model systems for research. AdvocureNF2 contributed as a Silver Sponsor.