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The Children's Tumor Foundation is delighted to announce our co-sponsorship of the third "State of the Art" International NF2 Conference to be held at the Manchester Conference Center, United Kingdom, May 21-22, 2012. The meeting will be hosted by the Manchester University NF2 Multidisciplinary Team.

The "State of the Art" meeting is a key event for the NF2 clinical and research community.  Past "State of the Art" meetings were held in Paris (2006) and Las Vegas (2010) and attracted attendance by the world leadership of NF2 clinical care, scientific and translational research, and clinical trials.  The 2012 meeting will focus on Epidemiology, Genetics and Natural History of NF2, NF2 Surgery and Radiosurgery, Auditory Rehabilitation and Animal Models and preclinical and clinical trials. 

Given the tremendous progress made in NF2 research and clinical trials in recent years we anticipate a very exciting meeting in 2012!  As with previous "State of the Art" meetings, the aim is to encourage discussion in a relaxed setting, and Manchester is sure to provide a unique venue.

For more information: http://www.nf2international2012.co.uk/

Malignant peripheral nerve sheath tumors (MPNSTs) are among the tumors that can occur in NF1, but these malignancies are particularly challenging to treat and control. One reason for this is that MPNST cells appear to undergo changes that make them reistant to traditional treatments such as chemotherapy. Cuurent Children’s Tumor Foundation Young Investigator Awardee Dr. Thomas de Raedt, a postdoctoral fellow in  the laboratory of Dr. Karen Cichowski at Harvard Medical School, has published a paper this week in leading journal ‘Cancer Cell’ describing his work in mice, showing a new and seemingly highly effective way to treat MPNSTs via a ‘double-hit’ - using two drugs in combination.  Dr. de Raedt and his colleagues combined the drug rapamycin, which targets the cell signaling element mTOR, with the drug IPI-504, which targets another cell signalling element called HSP90.  In the face of this treatment, the mouse MPNSTs underwent dramatic shrinkage. The tumors also underwent what is termed autophagy, where the cells die and collapse under stress so rapidly that they create spaces where the tumors were.  The success of this approach comes from the fact that combining rapamycin and IPI-504 leads to a collapse of cell structures called the endoplasmic reticulum (ER) and mitochondria which together, constitute the energy source or ‘engine’ of the cell.  By shutting down the ER and mitochondria, the cell dies.  We look forward to seeing the next steps of this exciting finding.

Dr. Cichowski and Dr. de Raedt are also members of the Children’s Tumor Foundation Neurofibromatosis Preclinical Consortium.

The goal of the Children's Tumor Foundation Drug Discovery Initiative is to fuel research that diversifies and advances the pipeline of candidate drug therapies for neurofibromatosis. Established in 2006, DDI Awards fills an important niche for the NF research community by providing modest 'seed' funds  - $15,000 for in vitro (cell) studies and $30,000 for in vivo (animal) studies to kick start new drug therapy ideas that might not have preliminary data, making it challenging to get initial funding elsewhere. The DDI Awards application process is easy and fast as only a 3 page research plan is required and  investigators can have the money 'in hand' as early as 6 weeks after the application deadline.  

Since 2006, DDI Awards has funded 45 drug testing studies that collectively cover NF1, NF2 and schwannomatosis manifestations including tumors, bone dysplasia, pain and learning disabilities.   To date CTF has invested around $1M in DDI Awards. We are delighted that we have been able to track this investment to a total of $5M in 'follow on' funding that the researchers have later secured from other sources such as NIH, DOD and industry.  In addition multiple industry collaborations have been forged by  NF researchers through DDI funding  and over 20 published scientific reports cite DDI funding. The next DDI Awards deadline is August 31st. In vitro ($15,000) and in vivo ($30,000) Awards are available.  Prior recipients of in vivo Awards with particularly promising data may be eligible to apply for a $50,000 Advanced DDI Award.   For application packet and information on past and current funded projects please click here.  General questions may be sent to Kim at khs@ctf.org

The following was written by CTF Chief Scientific Officer Dr. Kim Hunter-Schaedle:

Earlier this week the Children’s Tumor Foundation hosted a workshop/think tank convening 25 international researchers and clinicians to review recent progress in schwannomatosis research and clinical management, and set priorities to advance future progress. The meeting was planned and chaired by Dr. Scott Plotkin (Harvard/MGH), Dr. Marco Giovannini (House Research Institute) and Dr. Gareth Evans (University of Manchester) and included updates on genetics, cell biology, surgical intervention and the potential of advancing to clinical drug therapies for schwannomatosis, the rarest form of neurofibromatosis affecting an estimated 1:40,000 persons.

In part through CTF funded projects, significant progress has been made since the gene SMARCB1 (also known as INI-1) was in 2007 identified as a causal factor in inherited schwannomatosis.  Researchers have further unraveled the genetics of schwannomatosis, and learned that while SMARCB1 is important in inherited cases of schwannomatosis, this disease onset also involves the NF2 gene; and that in spontaneous (non-inherited) cases, SMARCB1 is not necessarily involved but that there are as yet unidentified genes involved.   The first mouse models of schwannomatosis tumors and pain are now developed and being used to study tumor and pain biology and test drug therapies.  And an international schwannomatosis database is established to collect information on schwannomatosis patients worldwide and facilitate future research projects and clinical trials.

At the workshop a series of priorities for the future was identified. There is a need to identify the additional genes and genetic modifiers that may be involved in interacting with the SMARCB1 or NF2 genes to lead to schwannomatosis. There is a need to develop more refined mouse models that represent schwannomatosis seen in humans as closely as possible, so that these can be used to study biology and tumor growth/pain and to test candidate drug treatments.  The biology and mechanisms of pain - which is such a central and poorly understood element of schwannomatosis - need to be unraveled and understood.  In terms of candidate drug therapies, it is rational to look at those drugs that are showing promise in mouse models of NF2 tumors, and see if they have impact on the tumors in mouse models of schwannomatosis.

Very importantly, now that we have a patient database, there is a need to plan clinical research studies to better understand schwannomatosis, such as understanding how individual patients condition has progressed following surgery, especially multiple surgeries; identifying whether there are blood-based or other biomarkers of schwannomatosis; and developing a pain survey for patients to better define the type and range of pain seen in schwannomatosis.; and looking ahead, prospective studies monitoring patients from time of diagnosis ongoing such as by whole body MRI. It is considered to be premature to consider clinical trials for schwannomatosis as we don’t have sufficient knowledge to do this; but that for patients in states of extreme crisis, there is the potential to begin testing drugs such as bevacizumab (Avastin) that have shown promise in NF2 patients.

Finally the clinical diagnostic guidelines for schwannomatosis were published in 2005 and the group reviewed these and made some recommendations to update these based on new genetics and clinical knowledge.

As a follow up to this workshop CTF will be spearheading the publication of a meeting report summarizing the latest update and recommendations for schwannomatosis. Also – in the next month – CTF will be releasing a Request for Applications to fund further schwannomatosis research.  After this great meeting we look forward to seeing further research progress.

On June 27th-28th the Children's Tumor Foundation is convening a Schwannomatosis Workshop (think tank) in Los Angeles. International expert researchers and clinicians will review the most recent findings in schwannomatosis research and clinical care, share progress and chart the future path to improving care and finding effective treatments for schwannomatosis.  I look forward to reporting the outcome of  the next 2 days of meetings. Below is a preview to set the stage.

I'll be staying in LA for the remainder of the week to attend the Acoustic Neuroma 2011 Meeting which includes a lot of NF2-relevant presentations, and will be reporting on that later in the week too. 
Schwannomatosis is the most rare form of neurofibromatosis affecting an estimated 1:40,000 persons. It causes the growth of multiple peripheral nerve tunors called schwannomas, and in addition it causes chronic, severe and unmanageable pain. There are no treatments for this. For a long time schwannomatosis was not well understood and in fact the first guidelines for its clinical diagnosis were not published until 2005.  A breakthrough came in 2007 with the publication of the first candidate schwannomatosis gene, INI-1/SmarcB1/Snf5. This gene has emerged to be a key player in schwannomatosis but interestingly there may also be involvement of the NF2 gene in the onset and progression of schwannomatosis. Schwannomatosis research faces added challenges as there are so few patients, so to accelerate progress CTF has brought this community of researchers and clinicians together since 2007 for a series of think tanks and they have shared and collaborated extensively with each other. CTF has been a major force in advancing schwannomatosis research in the past 4 years since the candidate gene was identified. In addition to hosting the think tanks, CTF has invested more than $700,000 in schwannomatosis research in this period. Projects we have funded include the creation of a schwannomatosis patient database now up and running;  the creation of the first 2 mouse models of schwannomatosis, both of which are now  being utilized for preclinical drug testing to reduce tumor growth and pain; and further genetics studies. Look for updates from the schwannomatosis think tank in the next day or so!