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NF Bites: Progress in NF2 – Part One

By April 7, 2010December 4th, 2023Awareness, NF2-SWN

Welcome to the fourth in a series of “NF Bites” – providing snapshots of individual areas of neurofibromatosis research and how the Children’s Tumor Foundation is advancing this. Over the coming days and weeks we will focus on different aspects of neurofibromatosis research. Today: the first of a two-part blog: where are we with NF2 research progress?

NF2 research activity, especially in the area of testing candidate drug treatments has increased significantly in the past several years. This has been driven in part by our publication in 2009 of consensus documents on NF2 clinical trials and drug pipeline in Clinical Cancer Research, based on an expert workshop convened by the Foundation. We currently fund a significant amount of NF2 research ‘from bench to bedside’ – an indicator of the exciting progress made in NF2 recently in understanding the underlying biology and then applying this to finding effective drug therapies.

Among our Young Investigator Awardees, Wei Li (Memorial Sloan-Kettering Cancer Center) has shown that merlin, the protein product of the NF2 gene, has a unique role in the cell nucleus. This work is published in leading journal Cell in February 2010 and will inform future NF2 drug design. Young Investigator Awardee Timmy Mani (University of Cincinnati) is examining a cell element called PIP2 as a candidate NF2 drug target. His promising data published in Molecular and Cell Biology in early 2010.   Young Investigator Awardee Chunling Yi (The Wistar Institute) is developing candidate treatment approaches for NF2 tumors focused on targeting merlin signaling as well as function of a protein called angiomotin; this is in progress.

Andrea McClatchey (Harvard/Massachusetts General Hospital) and Marco Giovannini (House Ear Institute) have received funding through the Foundation’s Drug Discovery Initiative Awards to test pan-erbB inhibitor CNX-222 from Avila Therapeutics in NF2 genetic mouse models and human xenograft models; and to test NXD30001, a novel Hsp90 inhibitor from Nexgenix Pharmaceuticals in mouse models of human NF2 vestibular tumor xenografts.  This work is underway.

Abraham Jacob (Ohio State University) received a Drug Discovery Initiative Award to test Akt inhibitor drug OSU-03012 in an NF2 vestibular schwannoma xenograft model. The drug showed promising data, inhibiting tumor cell growth. This data was published in the European Journal of Cancer and the drug is now in commercial development as AR-12 by Arno Therapeutics.

Joseph Kissil (The Wistar Institute) received a Drug Discovery Initiative Award to optimize NF2–targeting Pak inhibitors building on information as to how drug binds to receptor.

Marianne James (Harvard /Massachusetts General Hospital) has received a Drug Discovery Initiative Award to test mTOR inhibitors rapamycin, Torin1 and PI-103 on NF2 meningioma cells as candidate drug therapies.

Look for more NF Bites in the coming days and weeks!