Welcome to the sixth in a series of “NF Bites” – providing snapshots of individual areas of neurofibromatosis research and how the Children’s Tumor Foundation is advancing this. Over the coming days and weeks we will focus on different aspects of neurofibromatosis research. Today: where are we with research progress in NF1 learning disabilities?
Our understanding ofNF1 learning disabilities has opened up significantly in the past few years in terms of understanding their basis and developing treatment strategies – but we still have much more to learn and CTF is supporting this area.
· In 2005 Dr. Alcino Silva and his team at UCLA published a landmark finding. They showed that the cholesterol-modifying drug Lovastatin when given to a genetic mouse model of NF1 learning disabilities could reverse these deficits. Mice given Lovastatin had improved ability to respond in a test system called a water maze.
· Dr. Silva’s findings advanced rapidly to the clinic and Lovastatin trials are now well underway around the world through the CDMRP NFRP Phase II Clinical Trials Consortium as well as other independent clinical trials. Lovastatin offers the first hopeful drug for those with NF1 learning disabilities, but has also advanced other areas of NF, for example Lovastatin also show promise as a treatment for bone dysplasia (reported in an earlier NF Bites’).
· CTF Young Investigator Awardee Ana Oliveira (Duke University Medical Center) is examining the underlying changes that occur in brain cell in NF1 related learning & memory disabilities. She has found that cells in the brains of individuals with NF1 are actually different in their appearance and function.
· CTF Young Investigator Awardee Weidong Li (UCLA) is assessing Ritalin in mice as a candidate treatment for NF1 cognitive defects.
· CTF Young Investigator Awardee Linnea Vose (New York Medical College) is testing learning disabilities candidate drug treatments including rapamycin and rolipram in NF1 fly models.
· One of the challenged of early clinical trials was how to measure a drug’s effectiveness on NF1 learning disabilities. To more quickly advance discoveries from mouse to human, Dr. Nicole Ullrich and her colleagues at Children’s Hospital Boston have developed a ‘humanized’ water maze which is a computerized test. It is anticipated this ‘Arena Maze’ will be able to quickly determine if a drug is improving NF1 learning disabilities.
· In 2006 and 2007, CTF organized NF1 Learning Disabilities workshops to bring basic and clinical researchers in this area together. This helped in the planning of the ongoing Lovastatin clinical trials. Looking ahead we hope to again convene this community in 2011 to plan next steps. Of particular interest is the growing link between learning disabilities seen in NF1 and other genetic conditions. A next step is therefore to build on this common links and share data and ideas so that advancements can benefit not only those with learning disabilities in NF1 but also in the context of other genetic conditions.
Look for more NF Bites in the coming days!
