Another player has stepped into the celiac drug race. Intrexon a wholly-owned subsidiary of ActoBio Therapeutics has joined the race with approval for a phase 1B/2a drug trial in the US and Europe starting later this year.

There are three different types of drugs currently being evaluated – immune system modulators, ones that envelop the gluten protein and pass it through the system without damage, and ones that degrade the gluten protein before it gets to the small intestine to do damage. Most of the drugs currently in pipelines take one these approaches. There is one outlier – the larazotide acetate (INN 202) regulates the tight junctions between cells in the gut lining.

AG017 seems to be one of the degrading of the protein before it can do damage type combined with an immune system modulator. Specifically, they have engineered a bacterium called Lactococcus lactis that will express a gliadin peptide in “combination with immunomodulating cytokine.”

Let’s talk about what happens when gluten enters the body of a celiac patient. Gluten enters the stomach. Then the body dumps massive amounts of immune cells, over 15 different types of immune cells, into the body. These immune cells that are released are called cytokines and specifically, IL-2, IL-8, and IL-10 are the most prominent. At four hours after gluten ingestion, there is a 15-fold change in IL-2, an 11 fold change in IL-8, and a 1.2 fold change in IL-10. These cytokines are released by the gluten specific CD4+ T cells. It is this rapid onslaught of immune cells to protect us from gluten that causes celiac symptoms.

So if this peptide can block gliadin absorption and then correct the massive immune system reaction to anything that gets through its protection, we might have something that protects us from damage and from side effects. This is an interesting combination and makes a lot of sense.

Let’s see how this thing goes. It’s just another shot at help and evenutally a cure.

I saw a slide in a PDF that showed the number of compounds to the number of years and the number of volunteers needed to get a drug to market. This slide showed that out of 10,000 compounds only 1 might make it to market after 10 years of development and testing with over 4,000 volunteers.

When I first saw the slide, I was really, really discouraged about our chances for a celiac drug. Now that there is one drug in phase 3 clinical trials and several others either in phase 1 or phase 2 trials, we might get there sooner rather than later. By sooner, I really mean less than 5 years. I’m hoping that something will come along sooner, but it might really be 5 years. I think the phase 3 trial is expected to be done in December 2021. There is a lot of time between now and December 2021!

In order for these drugs to move forward, we have to be an active community. We have to volunteer for drug trials, we have to participate in research that maybe doesn’t involve drug trials, and we have to advocate with our Congress members.


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