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Two New ATP Studies Published

Focus on Neuropathology of Autism
April 23, 2007


Two autism investigators utilizing tissue from the Autism Tissue Program have recently co-authored new studies focusing on the neuropathology of autism.



The first is Christoph Schmitz, M.D., a NAAR-funded investigator at the
University of Maastricht in the Netherlands, who co-authored a new review of 25 published neuropathology papers dating from 1980 that gives an excellent perspective on what is known about changes in the brain. The review, “Neuropathological Findings in Autism,” was published in the August 25, 2004 edition of
Brain
. Dr. Schmitz and his colleagues reported on findings from the microscopic evaluation of post-mortem brains donated for research and vary widely in scope. Some are devoted to detailing the architecture of the brains, such as counting the number of cells, the size of cells, the density of cells and the arrangements of cell groups. Others use techniques that measure the amounts of the chemicals that guide the growth, organization and function of cells in different regions of the brain, and infer differences in gene activity. Age-related changes have been documented and constitute a major area of research.



Overall, the information since the first report in 1980 shows alterations in several brain regions and signs of both early embryonic, and post-natal, changes in the brains of autistic individuals. In the review, Dr. Schmitz and his colleagues also describe the
challenges ahead:



“D

ata from the limbic system and on age-related changes lack replication by independent groups. It is anticipated that future neuropathologic studies hold great promise, especially as new techniques such as design-based stereology and gene expression are increasingly implemented and combined.”



The authors of this review are evaluating a new set of 10 autism and 10 control brains from donors age 4 to 67, in collaboration with Jerzy Wegiel, V.M.D., Ph.D., of the New York Institute for Basic Research in a special
Brain Atlas Project
– which is funded by NAAR and supported by tissue from the Autism Tissue Program.



The
Brain Atlas Project
is important as it attempts to resolve some of the questions raised by the past research; mainly, whether structural changes are related to donor behaviors like language deficits, age, sex, cognitive ability, medical conditions, co-morbid disorders such as epilepsy and/or regression. The other projects, often investigating the same donor tissue, are also in the process of submitting data from their studies. A series of meetings are planned with the ATP Tissue Advisory Board members and various investigators to evaluate findings and establish research priorities.



In addition to Dr. Schmitz, a new study led by Carlos A. Pardo-Villamizar, M.D., of
Johns Hopkins University and pediatric neurologist Andrew Zimmerman, M.D., of Kennedy Krieger Institute, has also been published. Their study, which also utilized tissue from the Autism Tissue Program, is “Neuroglial Activation and Neuroinflammation in the Brain of Patients with Autism," and appeared in the November 15th online edition of the Annals of
Neurology
.



The investigation suggests that inflammation in the brain is associated with autism and that certain immune system components are consistently activated in individuals with autism.



“This exciting study highlights the importance of allowing researchers to directly investigate human brain tissue and represents an important step in understanding the role of the brain's unique immune system in autism,” said
Jane Pickett, Ph.D., director of the Autism Tissue Program. “I want to thank all of the families who have donated brain tissue and encourage others to consider this important “Gift of Hope.””



Dr. Pardo recently presented information on this study at a brain development workshop sponsored by NAAR that focused on the developmental neurobiology of autism. The workshop, "Integrating the Clinical and Basic Sciences of Autism" was held Nov. 12 and 13 in
Fort Lauderdale, FL and brought together approximately 100 neuroscientists and autism researchers.



Autism has a strong genetic component and appears more prevalent in some families with a medical history of the disorder. However, many researchers suspect the apparent rise in autism prevalence cannot be explained by genetics alone and that genetic abnormalities related to the cause the disorder may be influenced by environmental factors. In recent years, many studies have focused on immune system irregularities in children with autism. Dr. Pardo and his research team decided to focus on immune components inside the relatively sealed environment of the nervous system - as opposed to the overall immune system.



The team examined brain tissue from 11 people with autism, aged 5 to 44 years, who had died of accidents or injuries. This tissue was provided by the Autism Tissue Program, which is co-funded by NAAR, the Autism Coalition for Research and Education and the National Institutes of Health, in partnership with the MIND Institute at the
University of California at Davis.



Compared with normal control brains, the brains of the people with autism featured immune system activation and inflammation in the brain. Researchers measured brain levels of immune system proteins and discovered abnormal patterns that were consistent with inflammation.



The findings in the brain tissue were corroborated by studies of cerebrospinal fluid obtained from six children with autism (ages 5 to 12 years), in which cytokines that promote inflammation were found to be elevated.



"These findings open new possibilities for understanding the dynamic changes that occur in the brain of autistic patients during childhood and adulthood. Although they may lend themselves to development of new medical treatments for autism, much more research would be needed to establish the validity of this approach," said Dr. Pardo.



As a next step in this line of research, Dr. Pardo and his colleagues are studying how the genetic background of patients and families may influence the development of immunological reactions in the brain that confer susceptibility to autism.



Organ and tissue donation programs play a critical role in research efforts that are focused on finding treatments and cures for many diseases and disorders. For autism, that program is the Autism Tissue Program, which makes brain tissue available to as many qualified scientists as possible focusing their investigations on autism. To date, 38 principal investigators throughout the world are utilizing tissue from the Autism Tissue Program in numerous projects focused on solving the mysteries of autism. To learn more about the program or to enroll, please visit www.MemoriesofHope.org, or call 1-877-333-0999.