ja_mageia

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.

                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. 

Do you have a basic discovery that you think you can  translate to the clinic for the benefit of patients? The National Institutes of Health (NIH) Clinical Center has announced availability of funds for the 2012 Bench to Bedside Awards Program to support exactly this type of project. This unique program offers Awards of $135,000 over 2 years and supports clinical research - including in rare diseases such as neurofibromatosis. As part of its mission the program  faciliates access for researchers outside of the NIH to the institutes wealth of clinical research resources.  

A Letter of Intent is due on September 28, 2011.  More information about the program and the application process can be found at http://www.cc.nih.gov/ccc/btb/ or submit any questions by email to BenchtoBedside@mail.nih.gov.

Schwannomatosis is the least well understood form of neurofibromatosis and also the rarest, affecting an estimated 1:40,000 persons. It causes tumors to grow on peripheral nerves throughout the body and severe, untreatable pain.  In 2007 the first candidate schwannomatosis gene was reported but there is much to learn and understand on the path to developing treatments. Since that time CTF has been at the forefront of leading schwannomatosis progress investing over $600,000 in projects including  genetics, animal model development, preclinical drug testing and establishing a Schwannomatosis International Database.  As well as funding research, CTF has accelerated progress and collaboration in this area by hosting a series of expert consensus meetings, the most recent in June 2011 from which a state-of-the-field report is being developed for publication.

As an outcome of the June consensus meeting, CTF announces a request for Applications for Schwannomatosis Awards up to $75,000. Funding may be requested for ANY research in any area of relevance to advancing schwannomatosis; areas of emaphasis are Genetics, Cell Biology & Translational Research; and Clinical Research. Applications must be received by Monday October 3^rd, 2011. For more information visit http://www.ctf.org/For-Scientists/schwannomatosis-awards.html

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