New Treatments: EMIQ

In September of 2009, a study was conducted by researchers Hirano, Kawai and Arimitsu from the Department of Respiratory Medicine, Allergy & Rheumatic Diseases at Osaka University and published in Allergology International: Official Journal of the Japanese Society of Allergology. The study focused on the use of enzymatically modified isoquercitrin (EMIQ) in the treatment of allergic conjunctivitis. EMIQ is a type of nutrient called a flavonoid, that has anti-allergic effects. EMIQ and other flavonoids suppress cytokine release by TH2 cells. If you remember, TH2 releases IL-4 and IL-5, which stimulate B cells to differentiate into plasma cells and secrete IgE antibodies. IgE binds to mast cells and can effectively bind allergen to stimulate release of inflammatory mediators, such as histamine, from mast cells. Therefore, EMIQ inhibits the release of IL-4 and IL-5 from TH2.

The researchers divided 24 subject into two groups: one experimental group receiving 100mg of EMIQ and one control group receiving a placebo or pill with no therapeutic effect. Both groups of subjects were treated with their respective therapies, taking one capsule twice a day from January 27th to March 22nd in 2008. The groups received their treatments 4 weeks before February 22nd, which marked the beginning of Japanese cedar pollen release. Their symptoms of sneezing, nasal obstruction, ocular itching, tearing-up and conjunctiva congestion were measured every 4 weeks.

Based on the results, the experimental group expressed statistically significantly lower scores for ocular itching, tearing-up and conjunctiva congestion, compared to the control group. However, there was no statistically significant difference in scores for nasal obstruction and sneezing between the experimental and control groups.

In terms of allergic conjunctivitis, EMIQ alleviates ocular symptoms and may be an effective systemic treatment option. EMIQ still needs to be studied for long-term efficacy and safety. However, this study opens up an exciting new area of research for more natural systemic allergic conjunctivitis treatments. Researchers may want to explore other types of flavonoids that may have even better efficacy.

For more information about flavonoids Click Here

New Treatments: Blocking MCP-1

In November of 2009, a study was conducted by researchers Tominaga, Miyazaki, Sasaki, Mihara, Komatsu, Yakura and Inoue from the Division of Ophthalmology & Visual Science at Tottori University in Japan and published in Investigative Ophthalmology & Visual Science. The study focused on the effects of monocyte chemoattractant protein-1 (MCP 1) in the inflammatory response associated with allergic conjunctivitis. Before delving into the study, let's go into a little more detail regarding allergic reactions.

Allergic reactions can be divided into two categories: Type I immediate-type hypersensitivity or Type 4 delayed-type hypersensitivity (DTH). We are already familiar with Type I, which involves IgE antibodies on mast cells. If you remember, the process of Type I is as follows:

- Allergen enters the body and binds to receptors on a type of white blood cell called a B cell

- B cells digest the allergen and present it to a type of white blood cell called a CD4+ TH2 helper cell

- TH2 cells secrete some mediators that attract other types of white blood cells and other mediators called cytokines IL-4 and IL-5

- IL-4 and IL-5 induce B cells to differentiate into another type of white blood cell called a plasma cell, which then secretes the IgE antibody

- IgE antibodies bind to mast cells

- IgE antibodies are now ready to bind allergen, activating the mast cell to release histamine and other inflammatory mediators

Type 4 or DTH gets its name from the fact that it takes longer (about 1 - 2 days) for this type of allergic reaction to take place, whereas Type I is acute or immediate. DTH involves a type of white blood cell called a macrophage, which basically eats things. In DTH, the macrophage eats the allergen. The process is as follows:

- Attractive mediators secreted by TH2 cells in Type I hypersensitivity recruit other white blood cells, such as macrophages, to the site of the allergen exposure

- Allergen is recognized as foreign by the macrophage, which engulfs it and breaks it up inside

- Macrophage brings those tiny pieces of the allergen to its cell surface and presents it to another type of white blood cell, called a CD4+ TH1 helper cell

- TH1 cells secrete mediators or cytokines called IL2 and IFN γ

- IFN γ stimulates the macrophage to produce a substance called nitric oxide, which produces vasodilation or opening of blood vessels that leads to eye swelling and redness

- IL2 activates another type of white blood cell called a CD8+ cytotoxic T cell (CTL) which essentially kills other cells that have bound the allergen, resulting in eye tissue damage and pain

With all of the different types of white blood cells and cytokines it can get a little confusing, but the take-home message is that an allergic reaction begins with Type I immediate-type hypersensitivity. The longer the allergen stays in the body, the more activated Type I hypersensitivity TH2 cells are and the more likely macrophages will be attracted to the site of the allergen, increasing the chances of a Type 4 DTH.

In the study, the researchers found that injecting mice subjects with MCP-1 caused an allergic reaction, while blocking MCP-1 prevented the allergic reaction. Therefore, MCP-1 must play a key role in causing an allergic reaction. Through further analysis, researchers determined that MCP-1 did not affect IgE antibodies on mast cells at all, which suggests that MCP-1 is necessary for mast cell activation even if IgE binds an allergen. Therefore, blocking MCP-1 may be a new route of therapy for patients with allergic conjunctivitis. Also, blocking MCP-1 prevented Type 4 DTH from occurring after Type I hypersensitivity set in.

The results are interesting and goes to show that we don't know the whole picture for something that seems as simple as allergies. The more things we find are involved with allergic reactions, the more options the pharmaceutical industry has for designing drugs. Maybe the next new drug for allergic conjunctivitis will involve blocking of MCP-1. The fact that more and more mediators are being discovered only gives hope that one day a drug target may be discovered, in which the medication to alter it has an even larger safety profile than what is available today.

New Treatments: Cyclosporine A (CyA)

In March of 2010, a study was conducted by researchers Shii, Nakagawa, Yoshimi, Katsuta, Oda and Nakamura from the Research & Development Center of Santen Pharmaceutical Company in Nara, Japan and published in the Biological & Pharmaceutical Bulletin. This study focused on the use of Cyclosporine A (CyA) to treat allergic conjunctivitis. Cyclosporine is an immunosuppressant medication commonly used to treat patients who have received organ transplants. Cyclosporine eye drops have been used to treat pets, such as dogs and cats, with allergies. However, the use of cyclosporine to treat allergic conjunctivitis in humans hasn't been widely studied. Restasis is a cyclosporine product that has been used in humans, but its indication has been for dry eyes. The researchers in this study sought to study CyA specifically for allergic conjunctivitis.

In the study, researchers injected guinea pigs with a mixture of ovalbumin (OVA) and Freund's complete adjuvant (FCA), which are just chemicals that induce an allergic reaction. The guinea pigs expressed swelling and discharge from the eyes, suggesting the allergic response had taken hold. After six hours, the researchers used the CyA eye drops on the guinea pigs, which produced a decrease in discharge from the eye. However, CyA did not significantly decrease the swelling.

CyA did inhibit infiltration of white blood cells and fluid in the later stage of the allergic reaction. The researchers have concluded that CyA is effective in decrease late-stage symptoms, but does not alleviate symptoms related to the early-phase of the reaction. With the other medications out there, like anti-histamines and mast cell stabilizers, that work in both the early and late-stage phases of the inflammatory response, it may be better to just skip this one.

For more information about the history of CyA Click Here

For more information about Atopica, an ophthalmic CyA for animals Click Here

For more information about Restasis Click Here