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This blog entry was written by Dr. Kim Hunter-Schaedle and posted by Garrett Gleeson.

In just under a week’s time, the Children’s Tumor Foundation 2010 NF Conference kicks off in Baltimore. This year should see an attendance of close to 300 clinicians and scientists from around the world convening to share the latest developments in their neurofibromatosis research. The meeting is not open to the lay community, but through this blog and a series of short filmed interviews from the conference floor, our staff will keep you up to date on all the exciting research reported. 

This year’s NF Conference theme Back to the Future will celebrate the significant progress we have made in NF research in the past few years, but also focus in on the challenges that remain. The progress made in NF research has been impressive. Looking back, at the 2005 NF Conference, there were no talks on clinical trials. In 2010, we have an entire afternoon focused on the major ongoing clinical trials, with additional clinical trials presented throughout the meeting.  The same is true of preclinical drug testing – almost absent from the agenda just a few years ago – which now percolates through the entire meeting.  CTF has contributed to this progress, through the past few years’ implementation of our 2006 ‘Strategic Plan to Accelerate Neurofibromatosis Research to the Clinic.’ Miraculously, by the end of 2010 we should have set all five areas in motion, including: funding preclinical drug testing (ongoing through our Drug Discovery Initiative Awards since 2006 and NF Preclinical Consortium since 2008); establishing an NF Clinic Network (established 2007, now 42 clinics and growing); funding pilot clinical trials (to date two have been funded); establishing a Neurofibromatosis Patient Registry and BioBank (to launch in 2010) and identifying new NF biomarkers (ongoing through our various funding awards and to be expanded via the Biobank). Of course we never forget the value of ‘discovery’ research, and this year includes many presentations from junior investigators (many funded through CTF’s Young Investigator Award program), all the way up to the thought leaders in the field (many of whom were at one time YIA recipients!).

Follow the blog over the coming week for 2010 NF Conference previews, and of course for ‘live’ updates during the meeting itself!

After two very exciting but very long days of 'NF2: State of the Art', CTF kept about 20 scientists and clinicans on for a small workshop: 'NF2: State of the Trial'. The background to this  is that in 2007, CTF convened an expert NF2 group to figure out how we could accelerate NF2 clinical trials (at that time, not much was going on, certainly less than today). The outcome recommendations from this meeting - detailing how NF2 trials could be effectively done - were published in 2009 but were acted on much sooner by the docs, with the inception of clinical trials of bevacizumab (Avastin) Phase II, PTC 299 Phase II, and lapatinib Phase Zero as well as significant advancements in preclinical drug testing. Therefore we felt it to be time to reconvene the experts to ask are we doing as much as we can? What recommendations if any need to be updated? And, what resources are needed from CTF and other agencies (DOD, NIH) to support this? 
The outcome recommendations from the workshop are still to be distilled but in brief the group, under the auspices of CTF, is going to be publishing an UPDATE to the clinical trial recommendations just published last year - such has been the pace of progress! Looking ahead CTF will also be driving much more communication and collaboration between the 'mouse guys' and the 'clinical guys' - cross talk that will be essential to keep drilling and find the next promising drugs. Meningioma trials were discussed as a future focus in addition to further vestibular schwannoma focused trials. The NF2 clinicians are commited to commencing all-important discussions with the FDA, important to help this agency be familiar with NF2 in asvance of submitting drug applications. And importantly the group assembled has pledged to meet again one year from now and annually thereafter.
It has been a terrific few days of NF2 meetings and everyone left today feeling truly inspired about the future of NF2 trials. Look for a full report on the meeting soon at www.ctf.org!     

 Note:  apologies for not posting these Day 2 blogs earlier. Meetings were back to back today! An indicator of the huge amount of information exchange.

This afternoon focused on ‘Future Frontiers of NF2 Management’. The first three presentations focused on an NF2 and schwannomatosis genetics update (Ludwine Messiaen), an overview of England’s new NF2 national clinical management system (Sue Huson) and utility of three-dimensional imaging in NF2 management (Gordon Harris). Moving on to candidate therapeutics,  I gave a presentation on behalf of CTF offering some thoughts on issues the NF2 community should now be focused on as trials advance, including engaging industry, working with the FDA, and building links between preclinical researchers and clinical trialists. Marco Giovannini then provided a summary of his ongoing NF2 preclinical drug screening in the NF Preclinical Consortium and drug targets of interest including erbB, PI3 kinase and Akt.

Harry Miao of PTC Therapeutics provided an overview of the ongoing Phase II clinical trial of PTC-299 in vestibular schwannoma.  This trial is underway and has some positive but very preliminary indications of tumor shrinkage (notably vascular shrinkage). Scott Plotkin reviewed the status of the bevacizumab (Avastin) trial. This has doubled from the original 10 patients published last summer, and results continue to look promising with tumor shrinkage and some regained hearing, though responding tumors do re-grow when drug is stopped. In an exciting development, looking ahead, later in 2010 a second trial is set to commence in to give bevacizumab to children with NF2 who are 12 years and older.  

'NF2: State of the Art' closed with a terrific sense of promise and a commitment from the organizers to convene again in 2011. This evening we convened a smaller group for 'NF2: State of the Trial' to continue through tomorrow. This expert group will provide recommendations for programs to further accelerate NF2 trials. Higlights from this meeting will follow in a blog in a few days!  

After a packed morning and a very late lunch, this afternoon began with one of the most fascinating sessions of the conference, a presentation of individual challenging NF2 cases, and an expert panel discussion on how those patients should be managed. Debate developed around meningioma management, whether to intervene by removing a spinal tumor not currently presenting problems but with the potential to do so, and other topics. Interestingly with the emergence of bevacizumab as the first potentially promising drug therapy for NF2 (more on this tomorrow), discussions for the neurosurgeons are expanding beyond, ‘should we operate or watch and wait?’ to include ‘ would this patient be appropriate for the drug bevacizumab?’ It is exciting to hear surgeons thinking in this way, and as more candidate NF2 drugs come on line, potential alternatives to surgery will continue to expand. 

The afternoon closed out with a presentation from Rachael Hornigold describing a new NF2 Severity Score being developed in the United Kingdom. The Score takes into consideration both clinician and patient measures; currently 31 questions, the Score aims to get down to just 10 questions making it easy to use by any clinic. Interestingly when interviewed, NF2 patients said the two factors impacting most on their lives were facial paralysis and balance, features they felt set them apart from other people.   

 More to follow! Follow us on Twitter for 'live' meeting updates!

‘NF2: State of the Art’ got off to an exciting start this morning. Gareth Evans opened the day with a talk on NF2 genetics, and speculated that though the generation of merlin protein from the NF2 gene is truncated when there is a nonsense mutation, nevertheless some protein must be made that is able to bind to ‘healthy’ NF2 protein, resulting in tumor growth.  A trio of talks from Andi McClatchey, Helen Morrison and Filippo Giancotti focused on the cellular and molecular basis of NF2. These reviewed mechanisms of cell growth regulation by different functional domains and forms of merlin protein at the cell membrane and also in the nucleus, opening up a diverse array of candidate drug targets for NF2 drug therapies.   In an intriguing presentation, Anat Stemmer-Rachamimov reported data from an examination of tumorlets taken from NF2 patients. Tumorlets are tiny tumors embedded in the nerve and often identified only at time of autopsy, but are believed to be the predecessor from which full blown NF2 vestibular schwannomas develop.  A comparison of tumorlets and vestibular schwannomas from NF2 patients and seen quite a difference in genes expressed between the two tumor types. This may help unravel and separate out the signals that trigger the initiation, and then the advancement of growth, of NF2 tumors.

Switching late morning to NF2 tumor management presentations, Bill Slattery and Michel Kalamarides presented natural history studies from the United States and France, respectively. Natural history studies provide an opportunity to follow the natural progression of NF2 tumor growth etc. so that appropriate clinical management strategies can be developed.  There were a number of common features, notably the left and right vestibular schwannoma in a person will usually have independent growth rates. There was discussion about spinal tumors and whether these are likely to grow and require treatment. A percentage of patients will have spinal tumors requiring surgery often because of cord compression. Certain spinal tumors such as ependymomas may be largely inactive but potentially could be a concern in older adults.  Dr. Karajannis and John Golfinos focused on meningiomas in NF2 patients. These are likely to be more problematic than sporadic meningiomas, should be very closely monitored, and when operated on the whole brain picture needs to be understood to consider which meningioma areas are likely to require surgery next.

More to follow – please follow us on Twitter for ‘real time’ updates from the meeting!