Antabine (Anatabloc) and Autism - a Supplement or a Drug?

This is another post prompted by a comment received on this blog.

My 15 year-old daughter has classic regressive type ASD. I started her on an anti-inflammatory, Anatabloc, over a year ago and it allowed me to take her off atypical anti-psychotics ( she was on them for aggression) Do you know anyone else using this dietary supplement?  

I found this very interesting and so I did some quick research.

Anatabloc was until very recently sold in the US as a supplement, it was withdrawn from sale by the producer following a corruption trial and a dispute with the FDA over approvals.  Nobody is saying the supplement does not work, rather it is a drug.

Anatabloc, supplement at center of McDonnell trial, to be taken off the market

Anatabloc

Anatabloc was sold as an anti-inflammatory supplement based on a substance called Anatabine, found in tobacco and in lower concentrations in green tomatoes, green potatoes, ripe red peppers, tomatillos, and sundried tomatoes.

Anatabine has been studied in animal models and in cells to see if it might be useful for treating nicotine addiction and inflammation, and has been studied in models of diseases characterized by inflammation, such as Alzheimer's Disease, thyroiditis, and multiple sclerosis.

On a biochemical level, it appears to be active against certain nicotinic acetylcholine receptors.

Regular readers will recall extensive earlier posts on the cholinergic system and nicotinic acetylcholine receptors.

IBS, IBD and Autism, leading to Cholinergic Signaling and the Vagus Nerve

Nicotine Patches -Autism, Alzheimer's and MCI

Biomarkers in Autism: The Cholinergic system – In need of caffeine & nicotine or maybe just choline

The conclusion of all those posts was that, most definitely, in some people’s autism, an effective strategy is to adjust the cholinergic system.  Possible methods include:-

·        Vagus nerve stimulation – still in development

·        Nicotine patches – cheap and effective in some people

·        Two Alzheimer's drugs Donepezil and Galantamine, that are acetylcholinesterase inhibitors

So at first it seemed that Anatabloc may be “just another” cholinergic drug.  However on analyzing the patent submitted by the producer, it seems there may be an alternative mode of action.

Patent for Antabine use in Autism

METHODS OF ADMINISTERING ANATABINE TO TREAT AUTISM SPECTRUM DISORDERS AND SEIZURE DISORDERS

32| Anatabine is an alkaloid present in tobacco and, in lower concentrations, in a variety of foods, including green tomatoes, green potatoes, ripe red peppers, tomatillos, and sundried tomatoes. Without being bound by this explanation, data presented in Examples I and 2 below indicate that anatabine reduces transcription mediated by nuclear factor B (NFKB). NFKB is a transcription factor which operates in cells involved in inflammatory and immune reactions.

The nuclear factor NF-κB pathway

NF-κB is seen as being clinically significant in cancer and inflammation.

The NF-κB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-κB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules.  

NF-κB has long been considered the “holy grail” as a target for new anti-inflammatory drugs.

Because NF-κB controls many genes involved in inflammation, it is not surprising that NF-κB is found to be chronically active in many inflammatory diseases, such as inflammatory bowel disease, arthritis, sepsis, gastritis, asthma, atherosclerosis and others. It is important to note though, that elevation of some NF-κB inhibitors, such as osteoprotegerin (OPG), are associated with elevated mortality, especially from cardiovascular diseases.  Elevated NF-κB has also been associated with schizophrenia.

I take the, perhaps unconventional, view that schizophrenia is adult-onset autism.  It has already shown that in terms of genetics, there is a great overlap between these two conditions.

The interaction of nuclear factor-kappa B and cytokines is associated with schizophrenia.

CONCLUSIONS:

Schizophrenic patients showed activation of the cytokine system and immune disturbance. NF-kappaB activation may play a pivotal role in schizophrenia through interaction with cytokines

The Nuclear Factor NF-κB Pathway in Inflammation

Abstract

The nuclear factor NF-κB pathway has long been considered a prototypical proinflammatory signaling pathway, largely based on the role of NF-κB in the expression of proinflammatory genes including cytokines, chemokines, and adhesion molecules. In this article, we describe how genetic evidence in mice has revealed complex roles for the NF-κB in inflammation that suggest both pro- and anti-inflammatory roles for this pathway. NF-κB has long been considered the “holy grail” as a target for new anti-inflammatory drugs; however, these recent studies suggest this pathway may prove a difficult target in the treatment of chronic disease. In this article, we discuss the role of NF-κB in inflammation in light of these recent studies.

Clinical trials using Anatabloc

The producer behind Anatabloc is well advanced with clinical trials, as you can see below.

http://clinicaltrials.gov/ct2/results?term=anatabloc&Search=Search

I suspect that Anatabloc will disappear as a supplement and reappear a few years later on as an FDA approved drug for various conditions.

Conclusion

It is a pity that Anatabloc has been taken off the market.

It looks plausible that it could be effective in other people’s autism, not just the reader of this blog.

For the time-being, other than taking up smoking, a good source would be those tasty sun-dried tomatoes.

P.S.


Having re-read this post and taken a closer look at the patent and the company, I wonder if the original comment is genuine.  The patent is not very convincing and in Table 1 on page 44 it is quoting Wakefield et al, as one of only two sources that link inflammation to autism.  I could have written a much better patent application myself.