The 2011 NF Conference kicked off this weekend with some interesting and exciting presentations. On Saturday, Dr. Filippo Giancotti (MSKCC) provided an update on his novel research first reported in 2010 that described for the first time a role for NF2 merlin protein in the cell's nucleus. Dr. Giancotti has continued to unravel the signaling activities of merlin in the nucleus, and interestingly also showed that in sections of human meningioma tissue, merlin protein is not present in the nucleus. This would provide support for Dr. Giancotti's unique idea that merlin controls normal cell division and that lack of its nuclear function might be a factor in promoting NF2 tumor growth.
On Sunday, Dr. Alison Lloyd (University College London) chaired a session on the biology of peripheral nerve development and what we can learn from this and apply to understanding disease and specifically NF1. Dr. Lloyd herself presented some really interesting findings in mice where Erk signaling was disrupted in peripheral nerves by genetic mutation. The result is that the nerves undergo an inflammatory response, the blood nerve barrier function is lost and in short the nerve looks to all intents and purposes like they have been physically injured. Because Erk signaling is also disrupted in NF1 neurofibromas, this research opens the door to comparing this model of nerve injury to disease progression in NF1 tumors to see what one can teach the other. In the same session Dr. Luis Parada (University of Texas Southwestern) described an ongoing study in which he is screening pairs of drugs from a large compound library on malignant peripheral nerve sheath tumor cells. The study is beginning to identify potentially novel drug targets for the treatment of these NF1 tumors. Dr. David Largaespada (University of Minnesota) closed out the session with a report o his CTF-funded research focused on better understanding the exact nature of gene mutations that lead to neurofibromas, and how this can help us identify new drug targets.
On Sunday evening, Dr. Jaishri Blakeley (Johns Hopkins University) provided an update of her CTF-funded clinical trial of Lapatinib in vestibular schwannomas. This ‘Phase Zero’ trial is focused on giving patients drug prior to vestibular schwannoma surgery so that the excised tumor can be studied to see if the drug reached the target. This type of study provides a rapid preliminary evaluation to determine if a full scale Phase II trial is worthwhile. So far there is not compelling evidence that Lapatinib is effective but the trial is not yet complete so we look forward to seeing the final data. Dr. Fabio Nunes (Harvard) did a retrospective review of NF2 patients treated with bevacizumab (Avastin) for their vestibular schwannomas, to see if there were also additional effects on meningiomas. While there were modest effects of the drug in some tumors within some patients, this was not strongly compelling suggesting bevacizumab is not likely to be a promising therapeutic for meningioma. CTF Young Investigator Irma Rangel-Alarcon (UCSF) proposed a function for the protein encoded by the Spred-1 (Legius Syndrome) gene suggesting it has close interactions with the NF1 protein (neurofibromin) in the cell. This study could potentially help unravel why there is overlap in the clinical presentation of NF1 and Legius Syndrome.
Closing out Sunday evening Amanda Bergner (Johns Hopkins) provided an update of the CTF-funded Schwannomatosis Database which now has 14 US and international sites participating, has enrolled 27 patients and aims to have 200 patients registered by the end of 2011.
