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We mourn the loss of Congressman John Murtha, who passed away on Monday, February 8th, after complications from gall bladder surgery.

A former Marine Corps officer, Rep. Murtha was the first veteran of the Vietnam war elected to Congress in 1974, and focused on military affairs during his long and successful career in Congress.  As Chairman of the defense subcommittee of the House appropriations committee, he was a tireless advocate for our soldiers and their families.

Along with the breast, prostate, and ovarian cancer communities, the NF community owes Rep. Murtha a particular depth of gratitude.  Many of the key discoveries in NF have been made by projects supported by the Congressional Directed Medical Research Program (CDMRP). Rep. Murtha was a key figure in establishing this program in the 90's.  The program's  impact on the health of our military and their families has helped millions of others who have benefited from this work.

The CDMRP is an excellent example of what the federal government can accomplish - the funding has been very well invested and has a history of success that continues to build.   Please visit our Advocacy page (http://ctf.org/How-You-Can-Help/advocacy.html) to learn more and find out how you can help preserve this vital program.

John Risner

 

 

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

 

 

'What's New in Neurofibromatosis?' (links to abstract), the report from the Foundation's 2009 NF Conference, was published this week in the American Journal of Medical Genetics. Thanks to AJMG Editor-in-Chief Dr. John Carey  - we are excited to see this first publication of 2010 for the Children's Tumor Foundation on the heels of the two white papers published in 2009 (on NF2 clinical trials and bone dysplasia management).

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.

The congressionally funded Phase II Clinical Trials Consortium has just launched a terrific new public website. Three Consortium trials are now open: Lovastatin for learning disabilities; Rapamycin for plexiform tumors; and the newly added trial of Everolimus for optic pathway glioma. For more details on each trial, participating sites and entry criteria, as well as background information on the Consortium, please visit www.nfconsortium.org

The NF Consortium is dedicated to conducting clinical trials to improve the quality of life of persons with neurofibromatosis. The Consortium consists of nine clinical sites around the US and an Operations Center to coordinate Consortium activities at University of Alabama at Birmingham. It was formed in 2006 with funding secured through a Congressionally Directed Medical Research Program which has supported NF research since 1996, in part due to lobbying by individuals and organizations including the Children’s Tumor Foundation that represent the neurofibromatosis community.

 

 

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!

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.

 

At last week’s Partnering for Cures meeting, Kathy Giusti (who helms the highly successful Multiple Myeloma Research Foundation) described her initial realization that if things were going to change for multiple myeloma patients, MMRF needed to ‘host the party’  - i.e. take the risk, invest the money, develop the research infrastructure - then call industry to the challenge.  MMRF have pioneered the use of scorecards to keep metrics (measures of progress) on their team of investigators– keeping them on their toes and rewarding success with more funding. It is a controversial concept for some academic researchers but those embracing the MMRF model have had the joy of actually moving drugs forward to the clinic.  

As Debi Brooks (Michael J. Fox Foundation) described, today, donors (or as they are now widely being termed ‘philanthropic investors’) are much more engaged in the day-to-day of research project oversight than in the past, and they too want to see metrics and understand how their dollars are making a difference.  However as there are few if any miracles in life, it is important for the philanthropic investor to understand that success in research is more often incremental (e.g. “now we understand why the drug does not work and have another drug in mind to test”) than mind-blowing (e.g. “drug works, disease cured”).  Today’s philanthropic investors may now have a better acceptance of this risk than in the past, and the fact that there is a possibility of failure as well as success.

An important role for a Foundation is to maintain a ‘Landscape’ of the current state of research in their area (as the Children’s Foundation does), who is investing in it and what has been accomplished, so they can show the philanthropic investor where their ‘investment’ fits into the picture and how it is helping research progress. The Helmsley Charitable Trust has embraced the concepts of risk, money, metrics and landscape to inform their investments in Type 1 diabetes, a disease area that already receives sizeable funding from the federal government and the powerhouse Juvenile Diabetes Research Foundation and has attracted some industry interest. The Helmsley group engaged in a landscape analysis that identified two areas of need that they are now supporting: a mouse model of Type 1 diabetes to truly recapitulate the human condition; and a universal Type 1 diabetes patient registry.

More on Partnering for Cures later this week. 

NF2 researchers have puzzled over how the NF2 gene protein product merlin actually works in the cell. Why does this matter? Because understanding this will help us better figure out how to make drugs that correct merlin function in NF2 tumors and stop them from growing. In a new paper* (abstract) published in Molecular Cell Biology, Children’s Tumor Foundation Young Investigator Awardee Timmy Mani (University of Cincinnati) with a team led by his mentor Dr. Wallace Ip provide a new and unique view of merlin that might advance this area. It has long been known that merlin is related to proteins from the Ezrin Radixin-Moesin (ERM) protein family. ERM proteins are regulated by switching from a ‘closed’ to an ‘open’ conformation, and it has been thought merlin is the same. Mani and colleagues developed a series of probes that allowed them to ‘visualize’ merlin by fluorescence resonance energy transfer (FRET), as purified protein and in living cells. They found something new and unexpected: merlin exists in a stable, closed conformation but when activated undergoes a more subtle change than previously thought. These studies add to a recently growing body of evidence that challenge the standard thinking in the NF2 field. Also, though early stage, this type of research can inform the development of drug therapies aimed at targeting and restoring merlin function, and providing tumor treatments. This work was supported by the NIH, DOD CDMRP and the Children’s Tumor Foundation. * Hennigan RF, Foster LA, Chaiken MF, Mani T, Gomes MM, Herr AB, Ip W. FRET Analysis of Merlin Conformational Changes. Mol Cell Biol. 2009 Nov 2. [Epub ahead of print]