Page 4 AUTISM RESEARCH REVIEW INTERNATIONAL Vol. 20, No. 4, 2006 Editor’s Notebook: Biomedical Update: ARI’s ambitious agenda for 2007 (continued from page 3) More support for role of Gene affecting brain, GI, manner, and our six-month pilot test pro- oxidative stress immune systems may gram may begin as early as April. In a pioneering 2004 paper, Jill James play role in autism Other Projects and colleagues implicated oxidative stress as Each year, ARI publishes the results of its a culprit in autism (see ARRI 18/4). A new A common variant of a gene called MET treatment ratings survey. The latest data were study by the researchers supports and extends may double the risk of autism, according to compiled early this year (and are provided as their earlier findings. a new study. an insert with this newsletter). In addition, Oxidative stress occurs when rogue Daniel Campbell and colleagues note almost 1,200 parents of children and adults molecules called “free radicals” attack the that while most autism researchers are fo- with Asperger syndrome completed the body’s cells. James and her associates are cusing on genes that predominantly affect survey. We also analyzed the data for this focusing on two processes, critical to protect- brain development, individuals with autism population—see back side of insert. ing against oxidative stress, that appear to be often have gastrointestinal, immunological, Related to these results, I am writing abnormal in autism: or nonspecific neurological symptoms as a computer program to assist parents in • Methylation, a chemical process in which well. Campbell et al. decided to investigate selecting appropriate treatments for their genes are “turned on” or “turned off.” Meth- the MET gene because this gene contributes children. The program will ask parents to ylation affects the function of the entire body, to immune function and gastrointestinal indicate which treatments were given to including the immune and nervous systems. repair, as well as playing a crucial role their children and how well they responded • Glutathione metabolism. Glutathione in the development of the cerebral cortex to each one. Next, the computer program will is an important antioxidant (a substance that and cerebellum (brain areas that are often search through the database of more than helps protect the body against the effects of abnormal in autism). In addition, the gene 25,500 cases and find those individuals who heavy metals and other toxins). Low levels is located on a region of chromosome 7 that responded in the same way to those treat- of glutathione can lead to oxidative stress, is already linked to autism. ments. It will then provide a printout showing potentially damaging brain, gut muscosal, Campbell and colleagues analyzed the how well these “matches” responded to other and immune cells—all of which are often MET gene in a family-based study of 1,231 treatments. I hope to have this program up impaired in autistic children. autistic individuals. Many of the families and running on ARI’s Web site in 2007. The best measure of methylation capacity involved in the study were “multiplex,” ARI is very proud of its record of fund- is the ratio of two substances, S-adenosylme- meaning that they had more than one autistic ing “research that makes a difference.” thionine (SAM) to S-adenosylhomocysteine child. Unlike other autism organizations that fund (SAH). (This is called the SAM/SAH ratio.) The researchers discovered that children research, ARI funds only research that has When James and colleagues tested 80 autistic with two copies of the “C” allele of the gene direct implications to help children and children and 73 age-matched control children, were 2.27 times more likely to have autism adults alive today. Last year we funded they found that the autistic children’s SAM/ than children with two copies of the “G” vari- $500,000 in research. This year our aim is SAH ratio was significantly lower than that ant. The association of the “C” variant with to double this—funding more than $1 mil- of unaffected control children. Many autistic autism was strongest in multiplex families. lion. Of course, this goal will depend on the children also exhibited a dramatic reduction The researchers note, however, that the “C” generosity of our donors. in the ratio of “active” glutathione (GSH) to variant is very common, occurring in 47 In addition, I plan to travel the United “inactive” glutathione (GSSG). Cysteine, percent of the population, and does not in States this year to meet with parents and another substance needed for GSH synthesis, and of itself cause autism. professionals to keep them abreast of ARI’s was also significantly reduced. This indicates, Campbell and colleagues note that envi- endeavors, and visit autism clinics and re- the researchers say, that the building blocks ronmental factors most likely contribute to search facilities. In mid-February I’ll drive for GSH synthesis are insufficient. autism, and theorize that the “C” allele of north from San Diego to Seattle. I hope to The researchers evaluated genes known the MET gene—in conjunction with other visit various cities in the Midwest in May and to directly or indirectly modulate these genes and/or “epigenetic” changes (which June, and then the east coast in September. metabolic pathways, and found significant alter gene function but not structure)—can My “road trip” travel schedule will be posted increases in the frequency of certain genetic make some individuals more vulnerable to on ARI’s Web site. variants (polymorphisms) as well as signifi- these environmental stressors. Lastly, I want to thank everyone who sent cant gene-gene interactions. The researchers say that because of the cards and letters to me and to ARI’s staff They conclude, “We propose that an in- MET gene’s effects on different body sys- over the past two months. Your encouraging creased vulnerability to oxidative stress (en- tems, the gene variant could lead to “parallel thoughts and best wishes have meant a great dogenous or environmental) may contribute although independent” disruption of the brain deal to us. to the development and clinical manifesta- and the neurological, gastrointestinal, and tions of autism.” immune systems. — —SCHOOLS AND SERVICES— — “Metabolic endophenotype and related genotypes “A genetic variant that disrupts MET tran- The Autism Research Institute maintains are associated with oxidative stress in children with scription is associated with autism,” Daniel B. autism,” S. J. James, S. Melnyk, S. Jernigan, M. A. a list of schools and services for autistic Campbell, James S. Sutcliffe, Philip J. Ebert, Ro- individuals. If your facility should be Cleves, C. H. Halsted, D. H. Wong, P. Cutler, K. Bock, M. Boris, J. J. Bradstreet, S. M. Baker, and D. berto Militerni, Carmela Bravaccio, Simona Trillo, included on our list, and you believe W. Gaylor, American Journal of Medical Genetics, Maurizio Elia, Cindy Schneider, Raun Melmed, it may not be, please send a self-ad- August 17, 2006 (epub ahead of print publication). Roberto Sacco, Antonio M. Persico, and Pat Levitt, dressed, stamped envelope to receive Address: S. Jill James, Arkansas Children’s Hospital Proceedings of the National Academy of Sciences, our referral list questionnaire. Research Institute, 1120 Marshall St., Slot 512-40B, October 2006 (epub ahead of print publication). Little Rock, AR 72202, [email protected]. Address: [email protected].