Researchers Find Molecular Candidates for Treatment of Asthma and Allergies

La Jolla Institute for Allergy & Immunology scientists have identified the histamine releasing factor (HRF) molecule as a promising target for developing new treatments for a number of allergic reactions including asthma.

The research team, led by Toshiaki Kawakami, M.D., Ph.D., is also the first to clarify the role of the HRF molecule in promoting asthma and some allergies, including identifying its receptor – a major finding that answers a long-held and important question in the allergy research community.

The research study points to the development of new therapies based on blocking HRF interactions with certain antibody (IgE) molecules, long known to be central causes of allergies. The new study also found two novel peptides (N19 and H3) as strong therapeutic candidates for blocking the HRF and IgE interactions. two peptides inhibit the interactions of the HRF and IgE molecules, thereby stopping the allergic cascade in mouse models.

“Based on our preliminary studies, we believe these HRF inhibitors may provide a new, innovative therapeutic avenue for the treatment of asthma and some allergies,” said Dr. Kawakami, lead scientist on the study, published online in the Journal of Clinical Investigation.

Dr. Kawakami said the HRF molecule has been studied for many years and was thought to play some role in the cellular interactions leading to allergies and asthmas. However, its exact purpose and mode of operation was previously not clear. “Nasal drainage, skin blister fluids, and some bronchial fluids were found to contain HRF secretions, so the scientific community suspected that HRF was important, but we didn’t know why,” said Dr. Kawakami.

HRF studies had been limited by several factors over the years, he added, including the inability to model HRF interactions in mice. In addition, Dr. Kawakami said failure to identify the HRF receptor also slowed progress. “It’s very, very unusual for many years to pass between the discovery of a molecule and the identification of its receptor,” he said. “In this case, 15 years had passed. Without the receptor, we couldn’t understand the role of this protein in asthma and allergies.”

Dr. Kawakami and his team were the first to solve this mystery in 2007 — identifying a subset of IgE and IgG molecules as HRF receptors. This information gave Dr. Kawakami’s group the critical missing piece of the HRF puzzle and enabled the researchers to map HRF’s role in allergy activation.

Their study results showed that 20 to 30 percent of IgE molecules can interact with HRF molecules and produce mast cell activation leading to allergies. “We think HRF is important for amplifying allergic reactions initiated by IgE and an allergen,” said Dr Kawakami. The findings were published today in a paper entitled, Proinflammatory role of histamine-releasing factor in mouse models of asthma and allergy.