NYC area clinical trial for eczema therapy recruiting participants

A research group at Rockefeller University in New York City seeks participants for a clinical trial of an experimental therapy for atopic dermatitis. See below for details.

Dr. Emma Guttman-Yassky, Dr. Saakshi Khattri and others are exploring whether Stelara (ustekinumab), currently approved in the US for treatment of psoriasis, might benefit patients with moderate to severe AD whose condition has not improved with conventional treatment.

Ustekinumab is a monoclonal antibody to the p40 subunit of the signaling proteins IL-12 and IL-23. It binds to these proteins and prevents them from working. Since IL-12 and IL-23 are involved in the development of certain kinds of T cells, ustekinumab will put a damper on a subset of the T cell arm of the immune system.

I started to speculate about exactly how ustekinumab might work for AD but then I wisely looked at the researchers' own explanation on clinicaltrials.gov. I was only 25% right, so you'd do well to look at their writeup if you're interested.

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Randomized Pilot Study of Ustekinumab for Subjects with Chronic Atopic Dermatitis Who Have Sub-optimal Response to Prior Therapy

This study is currently recruiting participants.
Verified March 2013 by Rockefeller University

Sponsor:
Rockefeller University

Information provided by:
Rockefeller University

ClinicalTrials.gov Identifier: NCT01806662

Purpose
We are carrying out a clinical trial with the drug Stelara (ustekinumab), which is already FDA approved for Psoriasis, in patients with moderate to severe eczema, ages 18 years - 75 years.  In order to be eligible, a patient must have failed at least topical steroids and either light therapy or oral steroids. Patients will have 15 visits over the course of a year at Rockefeller University, which is located on the Upper East Side of New York City. Patients are guaranteed to receive 3 doses of Stelara throughout the study. Patients will also be allowed to use Triamcinolone 0.025% during the course of the study.  If the medication is effective at clearing a patient’s eczema, they will be eligible to receive an extra dose at the completion of the study.  For full participation, patients are compensated $600.

Name/Title of the Principal Investigator: Dr. Emma Guttman, MD/PhD

Contact Information:
Saakshi Khattri, MD - Clinical Research Fellow
1230 York Avenue
New York, NY  10065
Business number: 212-327-8354/8333
Fax number: 212-327-8232
Recruitment Office 1-800-782-2737
email: skhattri@rockefeller.edu

For more information, please visit:
http://clinicaltrials.gov/ct2/show/NCT01806662

Surprise: Th2 cells, inflammation high in both allergic, non-allergic eczema

When I talked to Jon Hanifin last year he mentioned an intriguing fact: eczema comes in two general types. About 80% of atopic eczema patients have allergies and high levels of IgE antibodies. But twenty per cent of patients have eczema without allergies.

The technical term for allergic eczema is “extrinsic” atopic dermatitis; the non-allergic kind is “intrinsic” AD.

Production of IgE—and most antibodies—is activated by type 2 helper T cells. So scientists have generally assumed that extrinsic AD patients had overactive type 2 helper T cells. But new research shows that type 2 helper T cells are overactive in both intrinsic and extrinsic AD patients.

The scientists, led by Emma Guttman-Yassky at Rockefeller University in New York City, analyzed skin and blood samples from 42 extrinsic and 9 intrinsic AD patients, looking at molecular and cellular differences in the immune system and the skin.

They found that type 2 helper T cell activation is actually higher in intrinsic AD patients than extrinsic AD patients. In fact, markers of inflammation in general are higher in intrinsic AD.

Figure 6 from the paper. Scientists now resort to "word clouds" to convey the complexity of molecular biology!

The results are surprising. Patients with intrinsic AD generally do not go on to develop asthma or allergic rhinitis; yet if you just looked at their helper T cells you’d think they were guaranteed to experience even more severe allergies than those suffered by extrinsic AD patients.

So what's keeping down the IgE levels in intrinsic AD? In the paper, the authors speculate freely, but so far there is no answer.

It also appears that a special class of helper T cells known as type 17 (so-called because they produce the signaling molecule IL-17A) are also more active in intrinsic than extrinsic AD. It’s not clear yet how scientists might  use this knowledge to design therapies more specific than current T cell-suppressing options such as ciclosporin, which can have severe side effects.

The research suggests that future T-cell related therapies will likely be similar for intrinsic and extrinsic AD, despite the different nature of the disease in the two patient groups.

Hat tip to KMO.