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This week saw a group of bipartisan senators - Sherrod Brown (D-Ohio), Sam Brownback (R-Kan.) and Al Franken (D-Minn.) - introducing the Creating Hope Act: legislation to encourage pharmaceutical and biotechnology companies to focus more intently on cures for rare diseases that affect children and which today have no treatments. A rare disease is one that affects fewer than 200,000 Americans. Neurofibromatosis affects 100,000, and has no treatment available, so could stand to benefit from this bill. The bill aims to offer incentives to industry such as faster approval at the Food and Drug Administration, and expands on a 2007 law offering "priority review vouchers" to companies that developed drugs for tropical diseases (this has also traditionally been a neglected area).  

This is another development in a series of promising changes that we have seen this year both in the government, and in industry, in terms of increasing interest in finding treatments for rare diseases.  Click here for article in 'The Hill'.

 

When we think about merlin (the NF2 gene protein), we probably think first about the brain and nerves where merlin protein regulates normal cell growth. When merlin protein doesn’t work properly, which is the case in individuals with NF2, vestibular schwannomas and the other nerve tumors associated with NF2 might grow, due to increased amounts of cell division. Now a new study* reveals that merlin also plays an important role in activating and regulating cell growth … in the liver.  The NF2 gene which encodes merlin protein was specifically deleted from liver cells in a genetically engineered mouse model, and this led to an immediate overgrowth of progenitor (stem-like) cells in the liver. This happened whether merlin gene was deleted in the developing mouse, or in the adult mouse.  The mice that survived this burst of cell growth went on to develop cholangiocellular and hepatocellular carcinoma – types of liver tumor. This liver cell growth in the absence of merlin protein seems to be driven by hyperactive signaling in the epidermal growth factor receptor (EFR) as the increased growth of liver cells could be blocked by treating the mice with anti-EGFR drug.

The study is headed by Dr. Andi McClatchey (Massachusett General Hospital) and authors also include Dr. Marco Giovannini (House Ear Institute). Both are NF2 site directors from the Children’s Tumor Foundation NF Preclinical Consortium.   This research points toward a brand new role for merlin protein in regulating normal liver development and growth.   Given the dramatic amount of liver cell growth and drug response reported, these mice may also be very helpful for initial testing of drugs intended as candidates for treatment of NF2 vestibular schwannomas and other nerve tumors.   

* Benhamouche S, Curto M, Saotome I, Gladden AB, Liu CH, Giovannini M, McClatchey AI. (2010) Nf2/Merlin controls progenitor homeostasis and tumorigenesis in the liver. Genes Dev. 2010 Jul 30. [Epub ahead of print]

 

The Children’s Tumor Foundation is offering a one-time deadline opportunity for researchers to apply for $100,000 Clinical Research Awards to fund NF1, NF2 or schwannomatosis pilot clinical trials or adjunct research such as biomarker studies in the context of an NF clinical trial. Innovative and broad-thinking ideas are encouraged! It is anticipated that up to four Clinical Research Award will be issued before year's end.

Letters of Intent are due September 15th; applicants will be notified of LOI review outcome in early October; and full applications will be due November 15th. Awardees will be notified in December and funding can commence immediately.   For more information and the LOI application packet click here or contact Kim at khs@ctf.org.
Reminder - this is a one-time deadline!

The CTF Clinical Research Award program replaces the CTF Clinical Trial Award program which is now closed.

Last week we learned that the US Food and Drug Administration was considering an advisory panel recommendation to revoke Avastin's use as a drug therapy for breast cancer. We are following this story closely as Avastin is now being used by a number of individuals with NF2 following published research showing tumor shrinkage and hearing restoration in some patients,  including the landmark  New England Journal of Medicine paper from Mass General in July 2009. Today the Wall Street Journal  reports that David Vitter, Republican Senator from Louisiana says that the FDA's decision is 'government rationing'.  Reports on Avastin's use have suggested that the lifespan of a breast cancer patient may be extended by the drug for just under 3 months on average.  Vitter, who lost his mother to breast cancer, and is an advocate for those living with breast cancer, slams the government for "assigning a value to a day of a person's life".

An FDA decision on this is no expected until the fall but we will watch this story closely, because drug access decisions made for one condition might well later have impact on drug access decisions for  another condition. CTF is currently conducting a survey of individuals with NF2 who are taking Avastin, and so far, though we have received a modest number of responses, it is clear that Avastin has offered hope  to at least a few individuals living with NF2. Once we have a critical mass of information we hope to make it more widely available and that if Avastin does show broader promise in clinical management NF2, this information might even help provide support for securing access to the drug for those who can benefit from it.