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Autism Speaks and the United Mitochondrial Disease Foundation Collaborate to Share Ideas

July 08, 2009

What might autism spectrum disorders, cancer, Parkinson's disease, and diabetes all have in common? According to scientists at the joint meeting of the United Mitochondrial Disease Foundation (UMDF), Mitochondrial Medicine Society (MMS), and the Mitochondrial Research Society (MRS) held two weeks ago in Washington, D.C., dysfunctional mitochondria may lie at the core of at least some forms of these and other chronic disorders.

This year's UMDF meeting included talks from several investigators in Autism Speaks' High Risk, High Impact (HR-HI) mitochondria workgroup, including Doug Wallace, Ph.D. from the University of California at Irvine (UCI), and Richard Haas, M.D., and Robert Naviaux, M.D., Ph.D., both from the University of Califorinia at San Diego (UCSD). Autism Speaks sponsored an afternoon symposium on autism and mitochondria with invited presentations from investigators in the workgroup providing evidence for a connection between autism and mitochondria. In his talk, Dr. Haas suggested a clinical path for identifying autistic children with possible mitochondrial dysfunction and the best practices for standard and cutting-edge diagnostic testing (Mol Genet Metab. 2008 May; 94(1):16-37). The audience also heard presentations on the state of the literature, arguing for further research from Salvatore DiMauro, M.D. (Columbia University), and Bruce Cohen, M.D. (Cleveland Clinic). The invited talks and the three abstract presentations that followed generated great interest and discussion from the investigators and families in the audience.

It is well known that mitochondria are "powerhouses" of the cell, responsible for generating the energy needed to perform a cell's many tasks. At this year's meeting another theme was prominent – mitochondria are integral to environmental sensing and intracellular signaling. In this broader view, dysfunctional mitochondria place more than just an energetic challenge on cells. Mitochondria that are not functioning properly change the communication within a cell that is essential for maintaining a stable nuclear genome, specifying RNA transcription, protein translation and making post-translational modifications. All of these changes can have potent effects on cells in the organ affected. Since the brain is the most metabolically demanding organ in the body, mitochondrial dysfunction frequently manifests as altered cognitive and motor function.

Although several reports detailing cases of mitochondrial dysfunction and autism have appeared in the literature in the last decade, recent recognition of the coincidence of immune, neuroinflammatory, and metabolic abnormalities in autism as well as some high-profile court cases involving regression, vaccines and mitochondrial disorders have attracted more attention to the potential role of mitochondria in autism. Last year, NIH and UMDF co-sponsored a session on mitochondrial encephalopathies in conjunction with the UMDF annual meeting (read a meeting summary here). This meeting initiated a conversation between metabolic and autism researchers and also identified an opportunity for a unique partnership of mitochondrial and autism experts from UCI and UCSD. This collaborative group is supported by the HR-HI initiative of Autism Speaks to probe genetic, metabolic and functional connections between mitochondrial and autism and also seek alternatives to the current invasive testing required for a definitive diagnosis.

During the autism session audience questions arose regarding the possible link between infection and regression in children with mitochondrial disorders. The moderator looked to HR-HI investigator Dr. Naviaux to address this topic. In 2002, Dr. Naviaux and his colleagues at the Mitochondrial and Metabolic Disease Center at UCSD were the first to draw attention to the important link between mitochondrial disease and common childhood infections. They found that 60% of children with mitochondrial disease had episodes of neurodegeneration, rather than fixed developmental delays (Arch Otolar Head Neck Surg. 2002; 128:355-362). They also found that infections trigger these episodes in 72% of the children. No studies have yet been published on the alterations in immune function in children with mitochondrial disease.

The scientific chair for this year's UMDF meeting was Doug Wallace, and during the meeting he gave multiple talks, to scientists and families. In his presentation on Mitochondria and the Epigenome, Dr. Wallace detailed how intermediates of oxidative phosphorylation – the energy production process in mitochondria – modulate the epigenome, effectively dialing up or down essential cell processes like transcription, translation, phosphorylation, methylation and acetylation. These epigenetic effects were linked to the modulation that the "genetic background" or haplogroup have on the severity of an inherited mitochondrial DNA mutation, explaining some of the extreme variation observed in presentation of mitochondrial disorders with the same mutation (PLOS Genetics. 2009; May 5(5): e1000474). Dr. Wallace also highlighted the fact that in many mitochondrial disorders males are disproportionately affected, much like in autism. One suggestion for why this would be is that estrogen appears to protect a female's mitochondria from the damaging effects of reactive oxygen species that are overproduced when a cell is under stress.

One of the unique features of the UMDF meeting was the coordination of activities among researchers and affected families. The AS staff members attending the meeting met several parents who reported that their children diagnosed with a mitochondrial disorder also had autistic symptoms and some offered anecdotal reports of a high coincidence of autism spectrum disorders in families with mitochondrial disorders. The meeting offered an excellent combination of primary research, medical suggestions for families in "Ask the Doc" sessions, awareness, family support and lobbying efforts for increased funding. The shared sense of urgency and family focus of the UMDF and Autism Speaks makes our ongoing partnership a special one that we look forward to strengthening. To that end, for next year's UMDF meeting in Scottsdale, AZ (June 17-19, 2010) we will continue our partnership with UMDF to host a larger autism symposium involving a broader range of topics and also a special "Ask the Doc" autism and mitochondria session for families.

For more information on UMDF visit their website at www.umdf.org.