Friday, June 12, 2015

New Research, New Hope Part 4 #FARECon

Rapid Suppression of Food Allergy by Dr. Finkelman

His Talk

He would like to use a rapid desensitization, a process which is currently most often used in patients who are allergic to a medication they need for a treatment, for food allergies. The idea behind rapid desensitization is that the patients are injected with increasing doses of the allergen every 30-60 minutes, starting with a dose that is too small to cause a reaction. In the case mentioned above (of a drug desensitization), the tolerance is temporary and the process can also be complicated by reactions, mild to severe.

Dr. Finkelman would like to develop an anti-IgE or an anti-FcεRIα antibody useful for rapid, permanent desensitization to all antigens. This would be a similar drug to  Xolair in function but he wants to improve on Xolair in the following ways: Xolair is slow acting, expensive, and does not work well in patients with high IgEs.

His lab began by injecting mice with an anti-mouse FcεRIα monoconol antibody (mAB). This resulted in a decrease in body temperature for the mice, which is an indication in mice of anaphlyaxsis. He then did rapid desensitization with the anti-mouse  FcεRIα mAB and was able to prolong sensitization to the anti-mouse FcεRIα mAB for 12 days after the initial rapid desensitization. 

The next step was to see if desensitizing mice using anti-mouse FcεRIα mAB would also result in a desensitization of any other allergens. So, they treated egg-allergic mice with the rapid desensitization method and did a food challenge and the mice were protected from their allergen. 

Dr. Finkelman's goal is to completely and safely suppress IgE mediated disease in under 24 hours.
He has five steps he says he needs to accomplish to meet that goal:

1. An anti-human FcεRIα mAB
2. Mice that have human mast cells or human FcεRIα on mouse mast cells
3. A food allergy model in mice that have human FcεRIα 
4. More rapid removal of IgE from mast cells
5. Back-up safety measures

They have already met steps one, two and four with trials using human FcεRIα on mouse mast cells and the  anti-human FcεRIα mAB. During these trials, they have been able to complete desensitization in less than 24 hours that lasts six days, but because of the expense of the antibody, they haven't had any longer trials.

They are still working on step three, making a food allergy model mouse. They do have a mouse currently that generate human mast cells, about 200 times the normal amount for a mouse, and human IgE. These would be a mouse equivalent for a human with mastocytosis.

In these mice, they have been able to achieve partial success with rapid desensitization. During the challenge portion, the mice have been desensitized still get sick, however they do not go into anaphylaxsis.

Dr. Finkelman said they are continuing to work on step five as well, trying a drug cocktail in addition to the anti-human FcεRIα mAB. With the mastocytosis mice, however, they continued to get sick, if not anaphylactic, so this is a portion they are still working on.

When the mouse studies are finished, they will need to test for safety and efficacy in monkeys prior to beginning a human trial.

During the question portion of the presentation, Dr. Finkelman was asked the dangers of removing nearly all of the IgE from the human immune system. His response was that this is something that is already been done, with Xolair patients, and in the Western world, as the risk from parasites was low, he did not believe it was a concern.

My Thoughts

When Dr. Finkelman said his goal was to suppress IgE-mediate diseases in 24 hours, my heart soared. How could it not? The path we are taking is years and here is someone, apparently not insane, who thinks that one day he will be able to travel the same path in 24 hours.

The thoughtfulness with which he laid out his research, he covered different variations, safety concerns, and went through step by step, impressed me.

That said, I think this may, one day, be an excellent choice for those most extreme cases of allergic conditions. Perhaps I am overly cautious of side effects, but as we have seen with Xolair, side effects continue to be found after the drug is approved. Xolair is amazing for those who need it, but not to be undertaken lightly. I feel the same will be true for this future treatment.

Secondly, I do wonder at the blasé response to the question of the IgE removal. IgE is not a vestigial organ like the appendix. It is true that we have few parasites in the Western world, however, people travel. 

For me, this treatment really boils down to need. If James had no other options and some allergic illnesses are that severe, it would sound amazing. With other options available, it sounds more like using a sledgehammer to kill a gnat.

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