Thursday, 20 March 2014

Dr Chez’s Trial of Lenalidomide, a TNF- α and IL-6 Inhibitor in Autism


An interesting trial of a TNF- α and IL-6 inhibitor in autism has been brought to my attention.  It was by Michael Chez, the neurologist from Sacramento, who has made several appearances on this blog.
By coincidence, a copy of his book arrived this week.  The book is called “Autism and its Medical Management”, Chez is one of the few mainstream doctors who does try and treat autism.  The book is rational, readable and in no way radical, so you could show it to your family doctor without upsetting him/her.  Chez does particularly focus on distinguishing regressive from non-regressive autism, as do I. His view is that it is regressive autism, even if it was regression from slightly abnormal.  The important part is that some learned skills, like language, were lost sometime after 12 months of age.  He believes that regressive autism has a different basis to non-regressive autism; he has his own ideas about this, but he admits there is no concrete proof.

The book is a few years old and Chez has published much work in the intervening few years.    
The paper I was referred to is:-

Lenalidomide, an analogue of thalidomide, has the potential to invoke significant changes in TNF-α and other immunomodulatory cytokines.  If thalidomide sounds familiar, it is the drug from the 1950s, that turned out to be very unsafe for use in pregnant women and around the world 10,000 babies were born with malformation of the limbs.

Lenalidomide has been used to successfully treat both inflammatory disorders and cancers in the past 10 years. There are multiple mechanisms of action.  It is extremely expensive, according to NICE:-

“Lenalidomide 25 mg capsules cost £4368 per 21 capsules (excluding VAT; ‘British national formulary’ [BNF] edition 55). Dosage is continued or modified based upon clinical and laboratory findings. For example, if lenalidomide is continued for ten 28-day cycles without dose reduction, the cost would be £43,680.”
Dr Chez does not mention the cost of Lenalidomide, but he uses a tiny dose of 2.5 mg; This would cost £20, or $30, a day.  This might also explain the small number (7) of participants in the trial.
“2.2. Drug and Dosing. Lenalidomide 2.5mgs was given daily
for 12 weeks. This low dose was selected to minimize the risk
of adverse effects. In addition, because this was a pilot study,
the goal was to test the lowest dose that could potentially lead to improvements.”
The drug did reduce TNF-α levels and there were some behavioral improvements, but nothing dramatic.  Perhaps a higher dosage would have had a greater effect?
There were only seven participants and the data on the seven is not complete; also the dose of Lenalidomide was very low.  I think it is really only fair to conclude that the trial is interesting but that a much cheaper drug would need to be found and tested on a much larger number of participants.

“Despite the limitations, to our knowledge, this open-label study represents the first attempt to treat autism by specifically targeting elevated innate inflammatory cytokine levels. Safety monitoring and pharmacokinetic data were successfully completed during this pilot study and exploratory observations of clinical and cytokine changes suggest a trend towards improvement. Correlating treatment outcomes with cytokine level changes may be a target in future autism spectrum treatment, especially in those with known maternal or postnatal immunological risk factors. Larger blinded and placebo-controlled studies assessing cytokine measurement and cytokine-targeted treatment in autism patients with TNF-α or other inflammatory cytokine elevation are warranted.”

To his credit, unlike the researchers in Athens who trialed Neuroprotek in a recent post, Chez went about his pilot study in a scientific manner and collected both the biological and the behavioral data.  In other words, he measured the before and after levels of the inflammatory cytokines and the before and after behavioral rating scales.  Well done Dr Chez.

1 comment:

  1. Dear Peter
    You can find Paul Whiteley's comments on this paper. I also feel this is not a good study. To get CSF sample for this study is traumatic.


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