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The NY Times published a three part series titled "Target Cancer" last week that is very informative.  While the focus is on melanoma, many of the issues the patients, researchers and clinicians faced during the trial are universal and have specific relevance to NF research.  

Story link:   http://nyti.ms/aV4iov

Patient advocacy groups like the Children's Tumor Foundation play many roles from funding medical research, providing support, resources and a community 'voice' for patients.  At the Biotechnology Industry Organization 2009 Annual Conference, a forum for pharmaceutical and biotechnology companies, and more recently for patient advocacy groups to interact and partner with these entities, CTF's Chief Scientific Officer Dr. Kim Hunter-Schaedle  featured in a short video highlighting the role of patient advocacy groups. View this now at

http://biotech-now.org/biodigest-patient-advocacy-011790.html

 

 

Recently published NF papers cover a range of topics. These include:  the controversial issue of using radiotherapy to treat NF2 tumors; how a patient's NF2 genetic status might predict severity of the condition;   molecular advances in understanding the function of NF2 protein merlin (by recent CTF Young Investigator Awardee Timmy Mani);  a role for the Spred-1 (Legius Syndrome) gene in controlling brain development and patterning; new zebrafish models of NF1 that have vascular and cardiac valve abnormalities; speech charasteristics seen in NF1 patients; and the first case of germ line mosaicism in schwannomatosis.  For more on what’s new in NF publications, read the January Research Roundup.

We are delighted to share with you that our colleagues at the Texas Neurofibromatosis Foundation (TNFF) will award $45,000 this year towards a research project benefiting the treatment of tumors and other manifestations of NF1, NF2 or Schwannomatosis. APPLICATION DEADLINE: February 20, 2010. RECIPIENT ANNOUNCED: April 9, 2010. Applications are welcomed from researchers WORLDWIDE. For more information and application materials contact Cindy Hahn at chahn@texasnf.org.

One of the few remaining ARRA opportunities at NIH is the RC4 program.  Areas of interest in this initiative are “Genomics/High Throughput Technologies” and “Translating Basic Science into New and Better Treatments”.  This initiative was just released on Dec 28^th; LOI deadline is 2/15 and submission deadline is 3/15.  Only projects with budgets greater than $500,000 total costs per year (for up to 3 years) will be considered. Visit:   http://grants.nih.gov/grants/guide/rfa-files/RFA-OD-10-005.html. Remember NIH and NINDS support molecular library screening (R21) and therapeutic development (R21 and U01) including for neurofibromatosis research. For inquiries contact Dr. Jane Fountain at fountai@ninds.nih.gov.

 

Following on from our participation in December's investor-style forum for non-profit foundations, Partnering for Cures, we are delighted to announce that the Children's Tumor Foundation has been invited by the Biotechnology Industry Organization (BIO) to present our neurofibromatosis research programs and drug pipeline  at the 12th Annual BIO CEO and Investors Conference (www.ceo.bio.org) in New York on February 8-9. This meeting is attended by investors seeking investment opportunities with biotech companies.  In the past couple of years a small number of research foundations have also been invited to speak. For the Children's Tumor Foundation this provides us an  opportunity to showcase our programs in preclinical drug screening and clinical trials, and  potentially identify  industry drug collaborations and new sources of funding. More news to follow!

Ed. note: The below was written by Dr. Kim Hunter-Schaedle.

This year has seen some amazing progress in neurofibromatosis research. The path to finding treatments for NF1, NF2 and schwannomatosis is challenging, but researchers continue to unravel the biology and apply this information to identifying candidate drug interventions. Here are five areas worth highlighting from the year. We blogged on most of these and you can find more information by searching our archive. 

1. Neurofibromatosis Clinical Trials Pipeline Grows. July saw the reporting of a small but groundbreaking NF2 clinical trial of bevacizumab (Avastin) at Massachusetts General Hospital yielding preliminary evidence that the drug could shrink vestibular tumors and lead to some regained hearing. This study published in top-notch New England Journal of Medicine and made the national media. The Foundation funded our first clinical trials, Phase 0/lapatinib in NF2 and Phase I/Sorafenib in NF1 plexiform tumors and published consensus recommendations for conducting NF2 clinical trials. Other neurofibromatosis trials commencing this year included Phase II/PTC299 in NF2; and light-based therapy for NF1 plexiform tumors.
2. Basic Science Knowledge in Neurofibromatosis Advances. New research on cancer signaling this year, including several projects funded by the Children’s Tumor Foundation, opened up understanding of what makes benign cells become malignant, why and how cells metastasize, and how molecular targets ‘communicate’. We have the first mouse models of schwannomatosis and NF1 dermal neurofibromas, while other NF mouse models are now improved to better replicate the human condition as closely as possible.  This information and these tools are vital resources for developing targeted drug treatments for neurofibromatosis.
   
3. Getting the Right Diagnosis. Legius Syndrome (NF1 like, but caused by SPRED1 mutations and with milder clinical impact) moved from lab to clinic as a bona fide condition that can be diagnosed. Explorations into the genetic cause of schwannomatosis evolved and we now know this definitely goes beyond the first candidate gene identified, INI1/SMARCB1; this area will benefit from the information collected from patients in the US and Europe through the Foundation’s new Schwannomatosis Database project. Also this year the Foundation published consensus recommendations for management of NF1-related bone dysplasia. As the clinical spectrum of neurofibromatosis and our body of information grows the Foundation shares this broadly across our NF Clinic Network, now 40+ clinics strong. 
4. Fuelling the Neurofibromatosis Drug Pipeline. The Foundation’s Drug Discovery Initiative funded nine DDI Awards in 2009 including our first schwannomatosis award - to screen pain drugs. DDI projects span NF1 and NF2 tumors, learning disabilities and bone dysplasia. Drugs tested range from commercially available drugs, to industry pipeline drugs, to new chemical entities. Perhaps most unique in 2009 we funded induced pluripotent stem cell (iPS) as a therapeutic approach to treating NF1 plexiform tumors.  To date we have invested $735,000 in 31 Awards - and already, prior awardees have collectively secured $3.7M in follow on funding and spearheaded 14 industry collaborations!  The Foundation’s NF Preclinical Consortium also expanded its industry collaborations to include Novartis, Genentech and Avila Therapeutics. 
5. Our World Evolves. We are in this together like never before.  Biotech and pharma are merging, streamlining and even collaborating on clinical trials that combine their drugs.  Operations at the Food and Drug Administration are being closely examined.  Even the inner workings of the NIH, awarded an extra $10B in stimulus funding this year, are under the microscope, and have an enthusiastic new director at the helm in NF1 gene pioneer Dr. Francis Collins. Foundations like ours are gaining a bigger voice by working together such as at the ‘Partnering for Cures’ meeting in December. And don’t forget the changing healthcare system. We hope this time of change will lead to easier access drugs and accelerated clinical trials that benefit those living with neurofibromatosis and many other conditions.

Doctors are often stymied in trying to prevent and treat the spread of malignant tumors throughout the body, not least when a tumor reappears in the original location after treating with surgery, drug or radiation. It has long been known that malignant tumor cells can send out ‘seed’ cells around the body to create new tumors.  Now it turns out – as reported* in this week’s issue of Cell (links to abstract) - that these ‘circulating tumor cells’ (CTCs) can also return to their tumor of origin to re-seed and perpetuate that tumor’s growth.  CTCs may even take ‘refuge’ in the bone marrow for a time before reappearing to seed or re-seed a malignant tumor.  In migrating to a tumor, the CTCs seem to be responding to growth factors called interleukins, secreted by the tumor.

The reporting team, based at New York City’s Sloan Kettering Cancer Center and headed by top cancer researcher Dr. Joan Massague, studied the behavior of breast cancer cells labeled with a fluorescent marker to allow easy tracking, and then implanted into mice. The finds may help explain why tumors grow back after surgical removal and drug therapy and hopefully help inform development of future treatment approaches for malignant tumors.

* Mi-Young Kim et al. (2009) Tumor Self-Seeding by Circulating Cancer Cells. Cell, Volume 139, Issue 7, 1315-1326, 24 December 2009.

 

 

Chronic conditions - like neurofibromatosis - by definition, last a lifetime.  Tracking the natural history of the condition (in other words, how it progresses during life) in as many patients as possible, and comparing findings between patients, provides important information that can be used to figure out which interventions and treatments are working best across patients.  This type of information is collected in a patient registry - an electronic log in which doctors can enter information about an individual’s health status.  Data entered regularly over a patient’s lifetime adds to a collective goldmine of knowledge that could help shape future clinical approaches.  

An article* in today’s New York Times highlights the fact that a patient registry can not only change the landscape of how a disease is understood and managed, but can vastly improve and even prolong individual lives. The Cystic Fibrosis Foundation (CFF) has blazed a trail in maintaining a registry that now collects patient information from 100 cystic fibrosis clinical centers around the country. In 50 years, cystic fibrosis has moved from being a condition of early childhood death, to one of adults living lives of dramatically improved quality. Much of this progress can be attributed to the CFF patient registry via its comparing  cystic fibrosis clinical management approaches and sharing these with the cystic fibrosis clinical management community. This registry has also fuelled CFFs  efforts in 'driving the bus' for cystic fibrosis clinical trials, an area CFF activated  alone long before the pharmaceutical and biotechnology became interested in rare diseases.  Patient registries are now being developed by many other Foundations, professional societies and even the National Institutes of Health.

Building on our NF Clinic Network established in 2007 and now comprising 40+ clinics across the United States, the Children’s Tumor Foundation is currently planning the implementation of both an NF patient registry and NF tissue biobank which we aim to launch in 2010.   In January, the Children’s Tumor Foundation will join with a number of other Foundations in an NIH-led meeting to plan for a collaborative patient registry that includes multiple diseases. This important step could make a patient registry possible even for extremely rare diseases where resources to do so are limited. 

* Tool In Cystic Fibrosis Fight: A Registry. New York Times, December 22.

 

With healthcare reform taking center stage in DC, the defense appropriations bill was pushed well beyond the new fiscal year that began on October 1st.

This year the House included $25 million in their version of the defense appropriations bill which was announced back in June.    This amount was reduced to $13.75 million during the conference process last week to reconcile the House and Senate versions of the bill.  Shortly after the Senate approved the final version of the bill President Obama signed it into law.

While the original $25 million was not preserved, the $13.75 million is a very welcome increase over the $10 million in fy 2009.  This increase comes at a great time, as NF research has made significant gains in the last several years, and is poised to translate these discoveries into new clinical trials.

Please take the time to thank your Representatives and Senators for preserving this vital research funding.

John