July 2007 Research Update

Thanks to the extraordinary efforts of the parents of children with AHC, we are moving ahead in our research program to identify the causes and potential treatment of AHC. In the last three years, we have focused our attention on evaluating “candidate” genes – genes that, for different reasons, may be responsible for the disorder. In the next three years, that important and difficult work will continue, but we shall also turn to a new phase of research into candidate treatments of AHC symptoms and promotion of awareness among the medical community. The search for genetic causes of any disease is vital, but it is also slow and painstaking. Many millions of dollars must be raised and many scientists must be engaged. Because AHC is both rare and complex, genetic research is especially challenging. Our work at the University of Utah, in collaboration with researchers at Harvard and UCLA, is promising, and it will continue. In an exhaustive search of 50 candidate genes, we have identified at least three families with specific mutations, 1 in the CACN1A1 calcium channel gene, and 2 in the ATP1A2 gene. However, to date, we have found that fewer than 5% of our AHC patients have one of those mutations. Thus, this work will continue, using newer more sophisticated gene chip techniques to help scan the entire genome for possible small changes in the genetic code that makes up our DNA. These results confirm what we already knew: gene analysis must continue, because it provides important clues to helping AHC patients, but we cannot wait for its completion before we begin the hard work needed to identify more effective treatments. We must figure out what we can do to improve the symptoms of AHC as we search for genetic causes. Thus, our new phase of research will expand into design of clinical trials that will test likely treatments. We have already begun plans to initiate the first clinical trial in this program, which will enroll a total of twelve patients. Our next step is to take this plan to the FDA and the institutional regulatory agency for approval. We hope to enlist the support of the pharmaceutical industry in these efforts, and to enroll the first patients by later this year. But the move to clinical trials to treat the devastating symptoms of AHC is not the only exciting news. All of us involved in the AHC community know that we need to increase awareness of AHC among pediatric neurologists and related specialists. We need to educate the medical and scientific communities to the importance of studying the disorder and providing optimal treatment. Thus, I am happy to announce that we have formed a fellowship program that will enable focused attention on AHC-related projects. Under my supervision and with the aid of a full-time study coordinator, each fellow will work exclusively on AHC. He or she will be actively involved in our clinical trial program and will also launch a specific mentored research project. The publications that ensue will further promote attention to AHC and help to generate enthusiasm and funding for future projects. Our first fellow is Dr. Matthew Sweeney. Dr. Sweeney received his bachelor’s degree in engineering at the University of Nebraska in 1997 and a master’s degree in bioemedical engineering at the University of Minnesota in 2000. He received his M.D. from the University of Oklahama in 2004. He has just completed his pediatric residency in June, 2007, and is committed to begin formal training in pediatric neurology in July of 2008. Thus, his background and interests make him ideally suited to contribute to advancements in our understanding and treatment of the complex problems faced by individuals with AHC. We are excited and fortunate for the opportunity to have him join us this year. We are confident that the continuing expansion of our research program to focus not only on genetic research but on clinical trials to help advance treatment options will prove fruitful and enhance our mission. The AHC foundation’s help in establishing funding for career-development fellowships is a big step in our battle against this terrible disorder. We believe that working together with families to explore new directions is our best hope for future success. Kathryn J. Swoboda, M.D. Principal Investigator AHC Project