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SYNODOS FOR NF2 On October 30, 2014, the Children’s Tumor Foundation held our first progress report meeting on the groundbreaking Syondos for NF2 initiative. Attendees included: SYNODOS PRINCIPAL INVESTIGATORS Jaishri Blakely, MD Johns Hopkins University Wade Clapp, MD Indiana University James Gusella, PhD Harvard Medical School Scott Plotkin, MD, PhD Massachusetts General Hospital
REVIEW PANEL Annette Bakker, PhD Children’s Tumor Foundation
Terry Van Dyke, PhD National Cancer Institute
STEERING COMMITTEE
FOUNDATION STAFF
Stephen Friend, PhD Sage Bionetworks
Lee Babiss, PhD Pharmaceutical Product Development, Inc.
Annette Bakker, PhD President Hyerim Lee, PhD Science Project Leader
Tracy Galloway, Patient Representative Bruce Korf, MD, PhD University of AlabamaBirmingham Gordon Mills, MD PhD, MD Anderson PP Pandolfi, MD, PhD Beth Israel Deaconess Harvard Medical School
This meeting was convened to assess the current state of the initiative after its first six months in operation. Synodos for NF2 was designed with five specific aims to advance NF2 research as quickly as possible. The five aims are: 1) Screen drug candidates against merlin deficient schwannoma and meningioma cells; 2) Collect and integrate molecular system data to define potential drug targets and improve the preclinical models; 3) Screen drug candidates in a variety of mouse models with vestibular schwannomas or meningioma; 4) Identify at least one drug candidate that has the potential to be brought to the NF2 patients for a clinical trial; and 5) to share data and manage all steps of the project smoothly and effectively. What follows is a brief look at where we stand after six months of this three year initiative. Aim 1: Screen Drug Candidates Synodos for NF2 researchers assembled a list
Annette Bakker, PhD Children’s Tumor Foundation Stephen Friend, PhD Sage Bionetworks
Marco Nievo, PhD Patent Attorney
Tracy Galloway, Patient Representative
Salvatore La Rosa, PhD, Synodos NF2 Project Manager
Bruce Korf, MD, PhD University of AlabamaBirmingham
Kimberly Scobie, PhD Scientist
Terry Van Dyke, PhD National Cancer Institute
Edward Stern, Counsel
of potential drug candidates that were either FDA approved or in late stage development. A discussion during which the investigators offered feedback based on their prior experiments led to the final set of drug candidates. They were selected based on: 1) relevance to known pathways in NF2, 2) feasibility for pre-clinical screening and, 3) availability. Screening of these drug candidates on a first set of an extensive panel of schwannoma and meningioma cell lines in multiple labs in parallel has been completed. The primary screening pipeline worked well and the Synodos researchers have shown real collaboration. Two monthly phone conferences are coordinated and managed by CTF. They are aimed at discussing the results, technical issues, important observations etc. By the next consortium meeting, the screening of the drug candidates on a second set of cells will be completed.
GLOSSARY Synodos: The term Synodos comes from the grouping of two ancient Greek words: syn and odos, which when combined mean ‘to work together on the same path’. Drug candidates: a set of advanced experimental or already FDA approved drugs which have a proven mechanism of action that could modulate a specific disease pathway. Drug targets: in the pharma industry it refers to a biological target which is a native protein in the body whose activity is modified by a drug resulting in a desirable therapeutic effect. Merlin: (also called Neurofibromin 2 or schwannomin) is a natural occurring protein. In humans, it is a tumor suppressor protein involved in Neurofibromatosis type 2. Screening: is a method that allows a researcher to quickly conduct millions of chemical, genetic, or pharmacological tests. Through this process one can rapidly identify active compounds, antibodies, or genes that modulate a particular biomolecular pathway. The results of these experiments provide starting points for drug design and for understanding the interaction or role of a particular biochemical process in biology.