By Henry Ehrlich
The outline for the next big step in the search for a cure for food allergy traveled from New York to Palo Alto in a purse. I know because I saw it Tuesday when I joined Dr. Xiu-Min Li and Dr. Kari Nadeau at a restaurant near Mount Sinai at Madison Avenue and 98th St. You’ve heard about Abraham Lincoln writing the Gettysburg Address on the back of an envelope? The doctors outlined the structure for a major study of oral immunotherapy for food allergies (OIT) on a paper napkin. As witness to this conversation (fly on the wall wouldn’t be fair to the restaurant) I had a glimpse of how science is conducted. Far from being a highly technical or detached process, this was a lively conversation between women who clearly like one another and want to bring their intellectual and institutional resources to bear on behalf of people they care deeply about: food allergic people of all ages, particularly children. “Chemistry” in this case describes far more than just what is measured back in the lab.
Kari, you will recall, achieved mainstream prominence recently in the New York Times Magazine for her OIT research at Stanford. Among the studies she has conducted are “rush” OIT, using anti-IgE drug omalizumab (Xolair) to reduce allergic reactions and allowing higher allergen dosing to expedite desensitization, and using Xolair to allow desensitization to multiple allergens.
Xiu-Min, who works with Dr. Hugh Sampson and the rest of the Jaffe Food Allergy Institute All Stars at Mount Sinai, is pioneering the use of traditional Chinese medicine (TCM) to treat allergic diseases including food allergies and asthma. Her Food Allergy Herbal Formula-2 (FAHF-2) has reversed anaphylactic peanut-allergy in mice and is now in advanced human trials. Dr. Li’s treatment differs from immunotherapy in that it modulates the immune system instead of in effect over-stimulating the production of allergen-specific IgE to the point of exhaustion, allowing non-allergic IgG antibodies to take up all the space on mast cells and basophils.
The crux of the project they discussed Tuesday is to test FAHF-2 as an alternative to Xolair for rush OIT and for multi-allergy OIT. This would be a tremendous advance because Xolair, while promising for these purposes, has some big drawbacks. It is really expensive, is administered only by injection (sometimes producing serious reactions), and can be very painful. It is currently used mainly for severe asthma and lately has attracted attention for helping with otherwise-untreatable chronic urticaria. By contrast, FAHF-2 in its latest highly refined version can be taken as six pills a day and is proven safe.
Both ends of this collaboration have institutional capabilities that can be shared. For example, Stanford has three staff members who specialize in the packaging of therapeutic doses of allergens for use in the trials. Mount Sinai has the connections in China for ensuring uniform, high-quality FAHF-2. Dr. Nadeau also mentioned that a great byproduct of the Times story is that she has received a huge volume of mail from patients asking for treatment, which comprises the basis of a larger research population than ever before, and which will be shared with collaborators at medical centers around the country.
After lunch we went back to the Annenberg Pavilion where Kari was to give a talk. On the way, we chatted about the plight of patients and their families. One thing she said really stood out. After observing that OIT is nothing new conceptually, having been tried a century ago, and should be more advanced, she said, “Science never got ahead of patients’ needs.”
The talk itself was noteworthy for several reasons. On a very superficial level, as one slide after another went up on the screen, with the authors of different studies listed under the data, as often as not three or four of them were actually sitting in the room. This was a high-powered audience.
More important was the description of variables from all European and U.S. OIT studies thus far published that make desensitization to food so hard to achieve: up to 98% of participants in OIT studies overall will have allergic reactions during the course of the study, and up to 10% of these reactions occur during home dosing. Up to 4% of these reactions are severe and need epinephrine intramuscular injection. Up to 20% of subjects tested with abdominal complaints had positive results for eosinophils in the esophagus. Dr. Nadeau said investigators around the country and Europe aren’t sure whether the appearance of eosinophils during OIT represents a phase parallel to the spike in IgE that accompanies regular dosing, is a new disease induced by the treatment for another, or whether it is there all the time and is “unmasked” by the close attention patients are paying to their health during study. An estimated 20% drop out rate due to non-compliance or untoward side effects has been reported in U.S. and european OIT studies. One thing is sure: no single treatment is going to work for every patient.
All in all, not a bad way to spend a few hours.