The final morning of the 2010 NF Conference included some great gems. Two parallel abstract sessions opened the day. One session focused on NF1 basic science abstracts; presentations included a significant focus on tumor initiation and malignancy and featured STAT3 as a candidate target for MPNST formation (Jianquiang Wu, Cincinnati), and two talks on the sources of cells that initiate tumor foramtion in NF and cause advancement to MPNST (Johanna Buchstaller, Michigan and Faris Farasatti, Kansas). The other session covered basic and translational NF2 research, notably including well-attended presentations of the Phase II bevacizumab (Avastin) clinical trials from Massachusetts General Hospital (Scott Plotkin) and Phase 0 and Phase II lapatinib clinical trials ongoing at Johns Hopkins University and NYU Langone Medical Center (Matthias Karajannis). As we reported from Las Vegas, these trials are moving forward and expanding; for Avastin there will be 2 US trials centered at MGH and Johns Hopkins respectively with different entry criteria. Additional NF2 talks in this sesion included Janet Oblinger (Ohio State University) with an update on NF2 preclinical drug screening studies using OSU-03012 which has shown some promise in animal models (these studies were originally funded by a CTF DDI Award).
A high-quality session closed out the day with the theme ‘across the Ras-MAPK pathway’ and touched on some aspects of neurofibromatosis not already covered in the Conference. Dr. Jonathan Epstein (U. Pennsylvania) reviewed progress in his research to understand cardiovascular manifestations in NF1, using zebrafish genetic models. Cardiovascular complications of NF1 are understudied but can be a significant concern; and they have come to the fore in recent years due to our increased understanding of the role of the inflammatory system in NF1. Zebrafish are transparent and allow Dr. Epstein to image vascular flow in living animals. The fish can also be bred easily with different genetic mutations making them a very useful model to unravel vascular complications. Having generated some fish with significant vascular provblems, Dr. Epstein can use these to test drugs that might correct the vasculature and could be NF1 clinical therapies. Dr. Dave Stevenson (Utah) gave a fascinating overview of the many bony abnormalities that affect an estimated 38% persons with NF1 and which are also seen in other ‘Ras-MAPK’ conditions such as Noonan syndrome. Dr. Stevenson is working with a colalborative group planning the first Phase II biologic therapy intervention for NF1 long bone dysplasia to commence later this year. This is exciting as today, children with long bone dysplasia often face amputation as the best available outcome. Dr. Eric Legius (Leuven) provided an update on Legius Syndrome. Dr. Legius actually saw the first Legius Syndrome patient in 1980; but it was many years later, in 2001, when the SPRED-1 gene was identified through studies in flies, that he defined the condition at the molecular and genetic level. Legius Syndrome has the appearance of ‘mild’ NF1 (cafe-au-lait spots; cognitive issues; mild bony malformations; but nerve tumors and vascular malformations seen only in very rare cases) and is due to mutation of the SPRED-1 gene on Chromosome 15. 142 patients with Legius Syndrome have now been identified worldwide. This is a very rare condition and includes only around 1-4% of individuals who have had a clinical diagnosis of NF1. As a next step, Dr. Legius proposed the organization of an international clinical an molecular database of Legius Syndrome patients so the conditio can be better understood.
The 2010 NF Conference ended with its traditional rousing cheer and lots of hope and promise. For me this ws the best NF Conference I have seen to date in terms of the quality of research ongoing and the advances made. Thanks to the 2010 NF Conference Chairs Sue Huson (Manchester) and Filippo Giancotti (Sloan Kettering) for putting on such a great event! Next: we hope for a professional publication of the 2010 NF Conference proceedings as we did in 2009.
2010 NF Conference: Final Day and Closing Thoughts
