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Zone in with Zon--Focus on ALS (Lou Gehrig's Disease)

Dr. Gerald Zon’s latest “Zone in with Zon” blog post, September 3, 2014, describes the origin and history of the recent phenomenally successful fund-raising effort known as the ALS Ice Bucket Challenge, as well as the current status of research on this terrible disease. For those of you who don’t know, the Ice Bucket Chalenge is an effort to raise funds for research on the disease amyotrophic lateral sclerosis (ALS), which killed the famous baseball player Lou Gehrig and is also termed “Lou Gehrig’s disease.” The ALS Ice Bucket Challenge involves dumping a bucket of ice water on someone’s head to promote awareness of ALS and to encourage donations—typically $100—to research on the disease. The challenge dares nominated participants to be recorded having a bucket of ice water poured on their heads, and challenging others to do the same. A common stipulation is that nominated people have 24 hours to comply or forfeit by way of a charitable financial donation. Although there is certainly an aspect of fun to this effort, Dr. Zon points out the grim reality that there is presently no cure for this deadly disease that affects 350,000 people around the globe and kills 100,000 annually. He further notes that the disease can impact anyone anywhere, regardless of age, ethnicity, or socioeconomic background. Although usually rapidly fatal, ALS does not always kill quickly. Famous British physicist Stephen Hawking has lived with ALS for many years and is now 72 years of age. Dr. Zon briefly discusses what is known about the genetics of ALS, while giving the caveat that the genetics appears very complex. He notes that a defect in the gene for superoxide dismutase (SOD) on chromosome 21 is associated with approximately 20% of familial ALS and approximately 2% of ALS cases overall, that is including sporadic or non-familial cases. Dr. Zon says that the mutant SOD gene has over 100 different genotypes. The most typical mutation seen in North American patients is associated with an exceptionally rapid progression from onset to death. On the other hand, the most common mutation seen in Scandinavian countries is different (D90A-SOD1) and patients with ALS attributable to this mutation live much longer, an average of eleven years. Dr. Zon further noted that, in 2011, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9orf72, which is associated with ALS combined with frontotemporal dementia ALS-FTD, and accounts for some 6% of cases of ALS among white Europeans. This gene abnormality is also found in people of Filipino descent. Dr. Zon expressed astonishment at the fact that in non-familial cases of ALS, or 90% of the cases, there is no known cause of th3 disease, and this accentuates the importance of the fund-raising effort for research. Dr. Zon notes his previous comments on the growing popularity of crowd-funding as a new, socio-web-based mechanism for “reaching out” to obtain money for conducting scientific research, including research on ALS. As an example, he describes Project MinE, an independent, large-scale, whole-genome research project that has been initiated by two Dutch individuals with ALS and was started on World ALS day (June 21) last year. Dr. Zon says that “Project MinE is a research project aimed at systematically interrogating the human genome for common and rare genetic variation in ALS—also known as genetic ‘data mining.’ The project will involve obtaining donated-DNA sequence information for 15,000 ALS samples and 20,000 healthy controls to obtain a large number of single-nucleotide polymorphisms (SNPs). This and additional sequencing will be performed on a sample size large enough to reliably analyze whole genome sequencing data outside of a family context. The long-term benefit of the approach taken for project MinE is a catalogue of many non-ALS whole genomes that can be used to investigate other human diseases, including diabetes mellitus, some types of cancer, and other neurological disorders. Project MinE is the largest genetic study worldwide for ALS and was started in the second quarter of 2013. Complete information—and details on how to donate may be found at the Project MinE website (http://www.projectmine.com/), which I encourage you to visit.” Dr. Zon closed with some exciting new results from Harvard University that may have a positive impact on ALS. The research results were described recently online by science writer Cynthia Fox in Drug Discovery & Development (http://www.dddmag.com/articles/2014/08/amid-als-mania-possible-drug-targ...). When the Harvard University scientists blocked a gene for prostanoid receptor DP1 in ALS brain glia cells in a dish, neurons made from human embryonic stem (ES) cells were “completely protected” from death. When the team created ALS mice with that same gene deleted, the mice lived 6.7 percent longer than mice with the gene. “We think this is a significant advance—both in terms of the use of stem cells for understanding disease, and with respect to understanding the degenerative processes of ALS and how we might inhibit them,” said the Harvard research team leader. Dr. Zon expressed his considerable hope that this will prove to be true, and very soon. Dr. Zon is an eminent nucleic acid chemist and Director of Business Development at TriLink BioTechnologies in San Diego, California. The entirety of this blog and previous Dr. Zon blogs can be viewed at the following link on the TriLink web site. [Zon blog post]