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.