Dear Friends, It is time to bring you up-to-date on our Center and overall ALS research activity. The 18th International ALS/MND Symposium took place in Toronto in early December 2007. The meeting had one of the largest delegations, more than 800 people from all over the world, and one of the largest numbers of presentations. In particular, poster presentations have increased not only in numbers but also drastically in quality in the past few years. Throughout the Symposium, I had a clear sense that basic and clinical research in ALS is progressing steadily, but at the same time, I had a feeling that we must have more studies that could fill in the right pieces of this complex jigsaw puzzle that is the mysterious ALS. One day before this International Symposium began, the World Federation of Neurology ALS Committee held a special symposium on Recent Progress in Genetic Studies in ALS. The last few years, an enormous effort has been made to collect DNA samples from the patients in the USA and throughout the world as well. As the first elected chair of the ALS Research Group, we made a unique effort to collect DNA (joint effort of the National Institute of Neurological Diseases and Stroke, MDA and ALS Association, along with nearly 70 ALS Centers in the USA), resulting in 2000 patient DNAs and 2000 DNAs from healthy controls. Independently, MDA researchers collected several hundred DNAs including controls. Similar efforts have been made in the UK and Europe. As the results of these DNA samples, a number of innovative genome-wise association studies (looking for a clue of single nucleotide polymorphism, SNP, abnormal genes associated with ALS) were carried out independently by at least 4 sites (NIH, MDA, European, and UK studies). Those results were published in leading medical journals last year. A puzzling fact is that potential genes associated with ALS that the researchers found in their studies were different from study to study. Although it is possible that ALS is likely to be made of many gene mutations and that country and racial differences caused such different results, these utterly different results have made us uneasy. I don't think such conflicting results mean a setback or regression in ALS research at all. A few years ago, we could not even imagine that these types of studies would be possible. But we now know that they are not only possible, we already have a few studies reported. We have been making enormous progress in building a strong foundation for the future of new genetic studies. No ALS geneticists doubt that there will be more genetic causes of ALS to be discovered or genes that suggest individual disease susceptibility, that is, anyone is prone to ALS. At the same time, we know a single gene is not enough to cause ALS or determine the ALS type but a combination of genes and factors beyond genes such as environment and lifestyle factors that would clearly influence not only the cause but also the onset and prognosis. We already have the right technology to study more genetic factors of this disease. We need more genetic epidemiology studies. In fact, 1000 or 2000 DNA samples may not be sufficient to resolve the questions just raised. We need to collect more DNAs along with healthy controls. That means that we need to have an effective system and sufficient funding to support tissue and body fluid banking. Such patient and control material will surely increase the research pace. Furthermore, we need to establish strong collaboration not just within our country, but clearly with international researchers. It is time to collaborate more cohesively. In this sense, on the last day of the Symposium, the Co- Directors of our Columbia Motor Neuron Center (Drs. Henderson, Przedborski and DeVivo) and myself (as the head of ALS Center) held an exploratory meeting with the researchers from the two principle ALS research centers in UK. Closer collaboration is another step in moving the research process faster and making it more diverse. During the Symposium, a number of satellite meetings were held. The ALS Research Group (now headed by Dr. Shefner, Syracuse) met to discuss how investigators can develop a mechanism of effective tissue collection. Clinical trial groups such as Northeastern ALS, Western ALS and Columbia CoQ10 Study groups had their own meetings to update the current status and future plans of clinical trials in ALS. Two very intriguing meetings were held: one was about a new potential clinical trial which is being developed in England using a type of food supplement. Another is a human embryonal stem cell therapy. Several clinical trialists who were invited all agreed that more basic animal studies are needed before we can consider clinical studies. Therefore, I feel there are exciting developments and I learned a lot at this Symposium. I hope you share my strong feeling that a lot is going on, far more than I can summarize in this Newsletter. For the New Year, I reviewed my commitment to continue to provide the best care and management for those who have this difficult disease along with the spouses and families who care for their loved ones. Research work and clinical care must come in tandem. Hiroshi Mitsumoto, MD