Anti-inflammatory treatments for autism

With the publication of our new paper (see the prior post), folks have asked, since bone marrow transplant (BMT) ameliorates several of the autism-like behaviors in our mouse model of maternal infection, are we saying that such transplants should be used in autism patients? Even though BMTs were also effective in a genetic mouse model of Rett syndrome (see the prior post), which displays some autism features, we do not believe that this should be pursued as a treatment for autism. This is a much too expensive and invasive treatment to be widely used for this common disorder. It would, however, be useful to collect information as to what happens when autistic children are given a BMT for leukemia – is there any change in behavioral symptoms during this potentially life-saving procedure? If any readers of this post have information on such cases, I would like to hear about it. See also blog comments from Paul Whitely.

Several alternative methods have been tested in an attempt to suppress the inflammatory-like state in autism. A new paper from Iran presents results from a double-blind, placebo-controlled study of the efficacy of the non-steroidal drug celecoxib over 10 weeks. With 20 children in the placebo arm and 20 in the celecoxib arm, very significant improvement was observed in irritability, lethargy/social withdrawal and stereotypic/repetitive behaviors. Since this was a double-blind trial, the well known expectancy effects in the parents can be excluded as an explanation for the positive results. It will be important to run this type of clinical trial in a much larger group of patients, and to collect data on markers of inflammation such as cytokines so as to assess the efficacy of the treatment and placebo on the immune system. That is, can the degree of behavioral improvement be correlated with changes in immune markers? It is also important to note that the minimal side effects found in this study were equally present in both placebo and drug-treated groups. It is known that adult use of celecoxib can sometimes lead to GI problems, so it is not clear how long children could be maintained on this regimen.

In a different approach, a 2007 case study tested the effect of pioglitazone (Actos) in 25 autism patients. This drug is also anti-inflammatory and is FDA approved for diabetes treatment. It is also being tested in variety of other neurological diseases. This study found significant improvement in irritability, lethargy, stereotopy and hyperactivity. The positive effects were much more pronounced in younger children (ages 2-6) than in older children and adolescents (8-16). This study was not double-blind, nor placebo-controlled, however. Thus, little confidence in this drug approach can be maintained until such a trial is done.

By the way, BMT has a positive effect in a mouse model of a genetic defect in which neurons in the cerebellum die. This may be due to replacement of microglial cells.

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18 Responses to Anti-inflammatory treatments for autism

  1. Sorry Paul that child didn’t appear to have a BMT this may be a more useful
    link to Marino Autism Research Institute at University of Miami

    http://pediatrics.med.miami.edu/mailman-center/research/mari/

    “We are also investigating possible linkages between autistic spectrum disorder and acute lymphoblastic leukemia, and will be leading an initiative supported by Autism Speaks, the Leukemia and Lymphoma Society, and the NIH to extend this to a population based study followed by a clinical intervention trial.”

  2. Katie Wright says:

    Thank you so much for doing this amazing and important work! This makes perfect sense. Prompt and comprehensive treatment can make the came make the difference between recovery and severe autism. Now we need a clinical trial in this country.

    Thank u again

  3. JBBW says:

    Has anyone looked into the mixed cell chimerism technique for a much less dangerous/invasive bone marrow transplant to treat autism? I saw that Dr. Suzanne Ildstad of the U. Of Louisville is studying its use in autoimmune disease.

    • phpatterson says:

      Thx Jllhrpr. I don’t know of any trials of bone marrow transplants of any type in human autism. The chimerism approach to autoimmune disease is interesting. Cheers,PHP

  4. Alex says:

    It is truly amazing to see the significant progress in the study of inflammation in the body. Thank you for sharing such fantastic information!

  5. NoName says:

    Hello Paul Patterson,
    as a sufferer from Schizophrenia who is taking neuroleptica I would like to thank you for writing “Infectious Behavior”, which changed my view on this mental disorder. I’m vegetarian and taking vegan aelge Omega3 (EPA&DHA) (Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases http://www.jacn.org/content/21/6/495.full ) and I already feel better after 3 month taking 650 mg a day. For a long time I had a red and itchy scalp, this condition improved a lot. However I still have gut problems, which I had for all my live even as a baby. Could it be that these conditions and my mental disease are somehow linked over the brain-immune link?
    Oh and I found three interesting and recent articles which might be of interest of you:
    1. The brains of people with schizophrenia are on ‘red alert’, study finds ( http://www.neura.edu.au/news-events/news/brains-people-schizophrenia-are-red-alert-study-finds )
    2. Researchers pursue red flag for schizophrenia relapse ( http://news.georgiahealth.edu/archives/6087 )
    3.Antibody-mediated encephalitis: a treatable cause of schizophrenia. ( http://www.ncbi.nlm.nih.gov/pubmed/22297586 )
    Might be worth a new blog post to share these information. Thank you.

  6. Kathleen says:

    Different, I know but I knew a boy in my son’s school program that had several blood transfusions and came out of the hospital talking. He didn’t speak prior to the hospitalization. Lots of curse words. Her son went back to school district and mine is in a private school for children with autism…so I don’t know if his progress continued.

  7. Anonymous says:

    Dear dr. Patterson,
    Have you heard about the neuroantinflammatory properties of sildenafil(viagra)? It has cured mouses with induced multiple sclerosis symptoms and it is thought to be useful for alzheimer.
    University of barcelona has published some findings. Do you think it could have benefit for autism?

    Thanks

    Best,
    Carlos Lucena

  8. Thanks for this. My little brother face the autism problem. Which treatment is best for him.

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