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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

This weekend the Children's Tumor Foundation participated with around 100 researchers,  clinicians and foundation representatives in the Second International Rasopathies Network Conference in Chicago.  The Rasopathies Network was conceived through a collaboration between physicians focused on, and families affected by, 'Rasopathies' - or rare diseases that affect signaling in the Ras pathway. Rasopathies include neurofibromatosis, Noonan's Syndrome, Costello Syndrome, Cardio-Facio-Cutaneous (CFC) Syndrome and Leopard Syndrome. These rare conditions share many common features, including learning disabilities, and skin and bone manifestations, with impact on quality and span of life. The goal of the Rasopathies Network is to drive collaboration between scientists working on the different rare diseases to accelerate research. The  2011 Rasopathies Network Conference was organized to occur at the end of a six-day schedule of family conferences and clinics for Noonan's, Costello and CFC families, which made for a busy and informative time.  Overall neurofibromatosis research has made significant advances compared to the other rare diseases and we  got some good words for our NF Clinic Network and preclinical programs.  But we can definitely learn from some of the approaches the other groups are taking, for example to develop patient health records, and to improve clinical care guidelines. As candidate drugs emerge, it is likely that they will have applicability across many of these rasopathies therefore ongoing communication is vital as the research moves forward.  At the close of the weekend CTF and the NF Network (formerly NF Inc) jointly participated in a small NF Symposium for local attendees where Alcino Silva (UCLA) and Maria Acosta (Children's National)  gave updates on learning disabilities research and trials; I presented some highlights from the recent 2011 NF Conference;  and Kim Bischoff (NF Network) gave a presentation on the importance of advocacy for NGF research funding. 
We looks forward to the 2013 meeting of this group, and to future collaborations with the Rasopathies Network and to both sharing our knowledge and learning a lot!
 

A team of researchers has identified the genetic mutation that causes Proteus syndrome, a rare disorder in which tissue and bone grows massively out of proportion. Only 300 people  worldwide are believed to be affected by this very rare condition.   The report appears in the July 27, 2011, early online edition of the New England Journal of Medicine.

It has long been speculated that the Elephant Man had Proteus Syndrome. It has been speculated too that in addition to Proteus Syndrome he may also have had NF1 gene mutations, but this has never been demonstrated conclusively. It is known that his clinical appearance would match a severe form of Proteus Syndorme.
The new discovery has broad implications for potential drug therapies and will also potentially inform neurofibromatosis research as well as cancer.  The team was led by researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health.
 
The mutated gene associated with Proteus Syndrome is AKT1, and is an oncogene i.e. it can promote the uncontrolled cell growth associated with cancer and as seen in Proteus Syndrome. Interestingly AKT1 has also been under consideration as a drug target for neurofibromatosis since it is on the same cellular signaling cascade. 

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!

Today we feature a Guest Blog featuring a report from the 2011 NF Conference from Dr. Fawn Leigh, a pediatric neurologist at the Massachusetts General and Harvard Medical School. Dr. Leigh presented the following project at the Conference, and is looking for further research collaborators, as well as any persons with NF1 who would be willing to participate and donate tissue, whether or not they are currently under care of an NF clinic.

At the 2011 NF Conference in Jackson Hole I gave a talk highlighting my findings from a pilot study to identify modifier genes that may inform the identification of potential drug targets and treatments in NF1. The study focused on a search for modifier genes of cutaneous (dermal) neurofibroma tumor burden in NF1. This was done through a genome-wide association study (GWAS).  300 NF1 subjects identified as having either the largest or least 15% of cutaneous tumor burden were genotyped using the Affymetrix GeneChip 6.0 platform. This provided 909, 622 single nucleotide polymorphism (SNP) markers and >946,000 probes for copy number variants (CNV).  The analysis revealed potential hits (P values of 10-4 to 10-7) with multiple SNPs at each of several regions of the genome. Each of these segments constitutes a candidate region that merits genotyping in an additional cohort of extreme subjects to either confirm or refute its modifier status, which is ongoing.  The CNV analysis is in progress. The current GWAS study is a collaboration of six centers across the world.  Five new centers recently joined this project. 

For researcher or patients seeking additional information about participating in this study, please contact:  Stephen Ranney (Clinical Research Coordinator)

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