Continued Funding for NF Clinical Trials Consortium

As we begin a new year, I’m pleased to report that our application for a third cycle of funding for the NF Clinical Trials Consortium has been approved by the U.S. Department of Defense (DoD).  The Consortium is a collaborative group of 21 medical centers across the country and one in Australia dedicated to conducting clinical trials of the most promising drug therapies for all forms of NF.  As the coordinating center for the Consortium, UAB serves in several critical leadership and managerial roles during nearly every phase of the clinical trials.  Although protocols for the trials may be developed at other medical centers, UAB is responsible for coordinating Institutional Review Board (IRB) approvals, collecting and analyzing the data, and facilitating the preparation of results for publication. This is a significant role that we’ve held since the inception of the Consortium in 2006 and one that reinforces our commitment to accelerating the pace of NF research by providing the opportunity for patients to participate in clinical trials throughout the country. The DoD reviews were laudatory of the Consortium’s contributions to the NF community as a major source of hope for NF patients seeking new approaches to treatment. It is encouraging that critical funding for this important research initiative will continue.

Results of Clinical Trial Show Effectiveness of New Drug

Next, I’d like to highlight the results of a small clinical trial of a new drug, called Selumetinib, published last month in the New England Journal of Medicine (

The study results are significant because they represent the first time a medication has demonstrated clear potential as a treatment in a clinical trial for plexiform neurofibromas in NF1.  This was a small Phase I trial conducted at the National Cancer Institute of 24 patients.  After receiving Selumetinib twice daily for a 30-month period, more than 70% of participants in the trial experienced a reduction in the size of the plexiform tumor. Additionally, symptoms of pain and pressure related to the tumors were reduced.  It’s interesting to note that this trial was developed as a consequence of previous animal model testing conducted by scientists funded by the Children’s Tumor Foundation (CTF).

The medication acts as an inhibitor of the RAS/MAPK cellular signaling pathway that is hyperactive in people with NF1. The RAS/MAPK pathway achieves its signaling through a complex form of cell communication that is also implicated in other disease processes, including cancer.  During the cell signaling process, each cell receives an intricate combination of signals that triggers many different signaling pathways in a cascading-like effect.  Neurofibromatosis type 1 is caused by a genetic alteration in the gene that encodes for neurofibromin, a protein that regulates activity of the RAS/MAPK signaling pathway. When specific signaling pathways become altered as in NF1, cells respond with uncontrolled growth. Selumetinib is one of a family of drugs that has been developed to inhibit components of the RAS/MAPK signaling pathway implicated in the development of cancer and other diseases. Because we now understand that NF1 has underlying genetic alterations that occur in this signaling pathway, we can test this family of drugs for their effectiveness in treating NF. The results of this study are encouraging because they represent the first example of a notably positive trial of a medication to treat NF.

A larger clinical trial of the drug with a greater number of patients is underway. Selumetinib is currently considered an experimental drug and is not available clinically, although a similar drug, called Trametinib, is clinically available.  While these are not harsh chemotherapy drugs, they do have potentially significant side effects and are not for every NF patient. Because of the demonstrated potential of the drug in the clinical trial, we are optimistic that this family of drugs will play a role in the future treatment of NF.  Also, the NF Clinical Trials Consortium is conducting ongoing trials of other drugs that work by the same mechanism, and additional trials will be launched in the future. The positive results of the Selumetinib trial are both exciting and significant for the future of NF research.