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Schwannomatosis is the rarest form of neurofibromatosis (NF), affecting an estimated 1:40,000 people, and it causes tumors to grow on peripheral nerves as well as severe and unmanageable pain.  It has also been the most mysterious form of NF, both in terms of accurate clinical diagnosis and in terms of understanding its biology and genetics.

In 2005, the Children's Tumor Foundation spearheaded the publication of the first diagnostic criteria for schwannomatosis.  In those initial critieria, it was stated that if a person had one or two vestibular schwannomas  (tumors on the 8th cranial nerve in the brain) then this would exclude a diagnosis of schwannomatosis and indicate a diagnosis of NF2.  In 2007,  the first candidate gene for schwannomatosis - INI1/SmarcB1/Snf5 - was identified, and though this gene does not appear to be universally involved in all cases of schwannomatosis, it has aided in the diagnosis of the disorder and in researching its molecular basis. 

Now a team led by Dr. D. Gareth Evans (University of Manchester) reports in the American Journal of Medical Genetics on two people each presenting with a unilateral (single) vestibular tumor as well as peripheral nerve tumors but for whom a diagnosis of NF2 has been eliminated through clinical or genetic evaluation.  This is an important finding, and suggests that there may be other cases elsewhere that have previously been diagnosed as NF2 that are in fact schwannomatosis.

The Children's Tumor Foundation has made significant contributions to advancing schwannomatosis research through grant funding, including establishing the first Schwannomatosis International Database, as well as organizing a series of International Schwannomatosis Workshops to spur collaboration.  In December, we'll be announcing some newly funded schwannomatosis research projects and unveiling future plans for our continued commitment to advancing this research area.

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/

                As neurofibromatosis clinical trials increase in number, the clinicians leading them are keen to design the trials to be as effective and meaningful as possible. A key part of this effort is developing the right trial endpoints - measures and metrics that can be used to determine if a drug or intervention is effective or not.  To tackle this area, a team of neurofibromatosis clinicians and researchers has formed  a working group called Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS). Spearheaded by Dr. Scott Plotkin (MGH) and Dr. Brigitte Widemann (NCI) and first convened in June at the Children’s Tumor Foundation 2011 NF Conference, around 30 leading NF clinicans and researchers participating in the REiNS met in Boston to continue their planning and discussions.

                Past endpoints for neurofibromatosis clinical trials have included changes in maximum tumor dimension on MRI scans or changes in cognitive function on neuropsychological assessment (for learning disabilities).  Looking ahead, more advanced endpoints under discussion (and already being piloted in some cases) include volumetric tumor analysis and whole body MRIs; and the use of biomarkers – biological indicators in the blood or other body fluids to determine if a drug is working. REiNS members have organized into groups to focus on different measures and plan to meet every few months to continue advancing this project.

                The Children’s Tumor Foundation is delighted to be investing in endpoint development through our Clinical Research Awards program.  Currently our funded projects include developing a computerized test for more accurate assessment of learning disabilities trials; identifying a blood biomarker of NF1 status; and developing measures of response for optic pathway glioma trials. We will be announcing more funded awards in early 2012. 

                Clinicians or researchers interested in participating in REiNS can contact Vanessa Merker at MGH: vmerker@partners.org. 

The Children's Tumor Foundation is delighted to announce that a Foundation-spearheaded paper outlining progress in NF2 clinical trials and strategies for further accelerating these trials has been accepted for publication in the American Journal of Medical Genetics.  This paper, "Consensus Recommendations for Current Treatments and Accelerating Clinical Trials for Patients with Neurofibromatosis Type 2" was authored by 17 international NF2 clinical and research experts as an outcome of a Children's Tumor Foundation-convened Workshop to accelerate NF2 clinical trials hosted in Las Vegas, NV last year.  Lead authors of the report are Dr. Jaishri Blakeley (Johns Hopkins University), Dr. D. Gareth Evans (University of Manchester) and Dr. Marco Giovannini (House Ear Institute). This is the second NF2 clinical trials consensus paper published under the auspices of the Children's Tumor Foundation. The first paper, published in Clinical Cancer Research and the result of a 2007 Foundation NF2 Workshop, helped initiate collaborations for the pioneering of NF2 clinical trials in the past few years. 

The new AJMG publication should appear in the near future.       
  

The Children’s Tumor Foundation (CTF) is delighted to announce the funding of five new Drug Discovery Initiative (DDI) Awards totaling $125,000, from applications received for our spring 2011 deadline.   DDI Awards fund studies to test candidate neurofibromatosis (NF) drugs for NF1, NF2 or schwannomatosis, offering $15,000 for in vitro cell-based screens, up to $30,000 for in vivo animal model screens and up to $50,000 to continue outstanding in vivo research projects.  Launched in 2006, it is one of CTF’s most successful programs.

The Spring 2001 DDI Awards are as follows:

Cristina Fernadez-Valle, Ph.D., University of Central Florida - $15,000
In vitro DDI Award to screen a small molecule drug library on NF2 Schwannoma Cells 

Jan Friedman, MD, Ph.D., University of British Columbia - $15,000
In vitro DDI Award to test cytokine inhibitors for the treatment of NF1 Vasculopathy

Xu Wu, Ph.D., Harvard Medical School/ Massachusetts General Hospital - $15,000
In Vitro DDI Award to Test Small Molecule Library of Inhibitors of YAP Nuclear Localization in NF2 Schwannoma, Astrocytoma, Meningioma Cells

David Largaesapada, Ph.D., University of Minnesota - $30,000*
In vivo DDI Award to test of drug combinations for NF1 Plexiform Neurofibroma and MPNST (builds on previous DDI Award of $15,000)

David Wiemer, Ph.D., University of Iowa - $50,000
Advanced DDI Award to optimize Schweinfurthins for NF1 Astrocytoma (builds on previous DDI Award of $30,000)

*Dr. Largaespada’s Award is funded by the Texas Neurofibromatosis Foundation through CTF.

Since its launch in 2006 DDI has funded 44 projects – around 10 per year – of up to $50,000 per Award, totaling a CTF research investment of just over $1 million. DDI studies up to 1 year to complete.  To date, 27 concluded DDI studies have shown promising results and have been successful in securing $4.7M in follow-on funding (to continue building on the CTF-funded research) including government, industry, state and institutional grants. 19 scientific publications have emerged from DDI research, and 19 projects have included collaborations with biotechnology or pharmaceutical companies.  And all of these numbers continue to grow.

DDI forms the backbone of the Children’s Tumor Foundation-funded NF candidate drug pipeline. Through DDI, the NF Preclinical Consortium, and the Clinical Trials Award program the Foundation is currently supporting drug testing bench-to-bedside from cell-based assays in vitro to pilot clinical trials.

The next deadline for DDI Award apps is August 31st and info can be found here.