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Tuesday morning included a session on new NF mouse models. Michel Kalamarides reported his mouse model of NF2 meningioma, in which these tumors can only develop if the NF2 gene is inactivated at a certain point in embryonic development.

Larry Sherman described his newly developed mouse model in which the schwannoma-related Brg1 gene is mutated.  Schwann cells derived from this mouse are hyperproliferative (divide too much) and make abnormally high levels of a growth factor BDNF; he is investigating whether this could potentially contribute to pain and a schwannomatosis phenotype.

Yuan Zhu presented a new mouse model that develops NF1 related of plexiform neurofibromas, dermal tumors and MPNSTs that are progressive and somewhat mimic the human state.  

The final session of the conference included presentations on new NF drug targets. Ronen Marmorstein is using structural design to optimize novel PAK inhibitors; this is partly in conjunction with Joe Kissil through a recently funded Children's Tumor Foundation DDI Award which will test them in animals with NF2 tumors.

Best 2009 Posters were a coup for Finland: Minja Laulajainen, University of Helsinki won Basic Science category for a merlin-focused study, and Lotta Alivuotila, University of Turku won Clinical category for a cognitive-focused NF1 study.  The 2009 NF Conference closed with the announcement of the 2011 NF Conference Chairs, Nancy Ratner and Michel Kalamarides. Before then of course, the 2010 NF Conference (‘NF- Back to the Future') - will take place in Baltimore, MD June 5-8, 2010 and will be co-chaired by Sue Huson and Filippo Giancotti.    

Eli Lilly has announced today it is opening up a web portal for collaborative initiatives with lab researchers around the world. The Lilly Phenotypic Drug Discovery Initiative, or PD2 (PD-squared), will employ Lilly's disease-state assays to evaluate compounds synthesized at university and biotech labs around the globe. After biological testing is completed, Lilly provides the outside researchers a data report including a complete biological profile of the compound across four assay modules: Alzheimer's disease, cancer, diabetes and osteoporosis. And Lilly says the in vitro model systems will provide researchers with broader assessments of a compound's biological profile than what is generally available today in academic or government laboratories. In return for the data, Lilly gains first rights to exclusively negotiate a collaboration or licensing agreement with the researchers who submit their compounds.

For more information on PD2, please log onto pd2.lilly.com.

Monday kicked off with a session focused on cognitive deficits of NF1 tackling topics such as the challenges of translating learning disabilities mouse research findings into human trials, as well as molecular drug target updates. This included results from testing drugs in learning disabilities fruit fly models (a well received presentation from Foundation-funded Young Investigator Linnea Vose). It is emerging that the clinical features of NF1 cognitive deficits are driven by many things in the brain, including potentially the way that some of the neurons (nerve cells) develop and ‘wire up' in the first place. Learning disabilities continues to be a really exciting and fast moving area of NF1 research.

Among today's NF2 presentations Vijaya Ramesh reported that cell signaling element mTORC, long recognized as an important candidate drug target for the treatment of NF1 tumors, may also be a key drug target in NF2 tumors meningioma and vestibular schwannoma. For example rapamycin which targets mTORC was able to shrink meningioma tumor cells - which are overly large -  back to a more normal size.   

 The theme of the 2009 NF Conference is ‘New Frontiers', a nod to the remarkable progress made in NF research and the tackling of new challenges, such as sorting through emerging clinical trial options. However, some truly brand new frontiers remain. Schwannomatosis, the rarest form of NF, causes peripheral nerve tumors and unmanageable pain. A candidate gene for schwannomatosis, called INI1, was identified just two year ago, but many mysteries remain. Are NF2 mutations also involved in schwannomatosis? What about other genes?   Some of these issues were addressed in a session Monday morning. A major challenge to answering these questions is lack of patients, since many clinics will at most see only a handful of schwannomatosis patients, and a lot of the patients are being seen elsewhere perhaps in pain or plastic surgery clinics. For this reason the Children's Tumor Foundation is supporting a special initiative to establish a collaborative schwannomatosis database that will collect patient data from as many clinics as possible. On Monday evening representatives from about ten clinics US and international met to hammer out the questions this database must ask - these need to be detailed enough to make the data collected ‘mineable' (searchable, meaningful) to identify patients for follow up studies. Also though, at the first cut, the amount of data to be entered can't be too onerous as to put clinics off taking the time to enter it. The Foundation is providing initial funding to get this database up and running, but perhaps our most important role in this will be to encourage and drive as many clinics as possible to participate. We are very fortunate that this effort is being driven the enthusiastic Allan Belzberg and Amanda Bergner at Johns Hopkins and excited to see it move forward.   

Friday saw a pre-conference meeting of the Children's Tumor Foundation NF Preclinical Consortium (NFPC), a collaboration of six top-tier labs - at UCSF, House Ear Institute, Washington University, Cincinnati Children's Hospital Medical Center and two groups at Harvard Medical School - each focused on genetically-engineered mouse models of different NF tumors.  Individually, these are highly successful NF research groups; collectively NFPC is a preclinical drug testing powerhouse. Drugs are tested in parallel in the multiple tumor types of NF1 and NF2 to ensure that we do not miss an opportunity: if a drug is not effective in one NF tumor type we can see if it might be effective in another. NFPC is overseen by a committee of seasoned researchers, many from industry, some with 20+ years of experience in drug development. A $4M multi-year commitment for the Children's Tumor Foundation, NFPC should maximize our chances of identifying drug candidates for NF clinical trials. So far NFPC has made tremendous strides, attracted a collaboration with Novartis and further industry partnerships are in planning.

An important element of advancing interesting preclinical drug candidates is to establish a link with the clinical trialists. That in mind after NFPC met Friday we had a one hour ‘crossover' meeting with the physicians of the Phase II NF clinical trials consortium which is funded by the Congressionally Directed Medical Research Program.  This group is a clinical trials version of NFPC connecting multiple clinical sites. Because of the variety of tumor types (plexiform, optic pathway etc.) and other manifestations (bone abnormalities, learning disabilities) seen in NF, an effort like this is required in order to recruit sufficient patients for a clinical trial in a timely manner. In the past year or so the Clinical Trials Consortium has launched 2 trials (for plexiform tumors and learning disabilities) and more are pending.

Scientists and clinicians can often live in two different worlds but the joint meeting of the 2 groups opened a dialog on the drugs in the preclinical pipeline, and those most likely to be of clinical interest. Though early days, this meeting emphasizes the importance of collaboration and open communication among our NF community to ensure that we advance promising drug treatment as quickly as possible to the clinic. We should see this theme continuing through the 2009 NF Conference.

Each year the NF Conference provides an opportunity for many events and meetings that are ancillary to the Conference itself but a vital part of NF community activities. This includes meetings of Foundation Boards and Committees as well as meetings of research consortia such as our NF Preclinical Consortium and the CDMRP NF Clinical Trials Consortium.  On a special note on Thursday June 11, the Oregon Affiliate of the Children's Tumor Foundation will host an NF Symposium for patients and families at Oregon Health Sciences University. An anticipated 60 attendees will hear Foundation program updates from me, as well as clinical trial and research updates from Dr. Bruce Korf (UAB) and Dr. David Viskochil (University of Utah) (in town for the Conference) as well as local Foundation-funded researcher Dr. Larry Sherman (OHSU). We are delighted to keep a local connection at the Conference by including three local lay presenters to share their stories of living with NF. 

Preparations for the NF Conference begin well over a year in advance - from selecting venue to developing the agenda with the chairs, inviting speakers, and securing sponsors. I would like to offer some ‘shout outs' before the conference gets started. We thank the 2009 NF Conference Chairs Dr. Kathryn North and Dr. Joe Kissil for their significant efforts throughout this year's planning and for responding to the hundreds of emails that went back and forth between us. We are delighted to recognize the supporters of the 2009 NF Conference: the National Institutes of Health, Novartis Institutes for Biomedical Research, the Biotechnology Industry Organization and PTC Therapeutics. In addition we thank the New York University office of Continuing Medical Education for their patience and guidance in facilitating CME accreditation for the 2009 NF Conference for the first time.