Japanese Red Cedar: A Story of Beauty & The Beast

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Audra Stanley
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1 Japanese Red Cedar: A Story of Beauty & The Beast

3 Japanese Red Cedar: A Story of Beauty & The Beast by Robert Rager & William Hearl For Immunomic Therapeutics, Inc.

4 About The Authors Bill Hearl, the founder and CEO of Immunomic Therapeutics, is a scientist and experienced bioentrepreneur. He has worked at a number of leading firms in the biotech industry and was the founder of Capital Genomix, Inc., a company based on genomic an d an tib od y d e v e l op me n t te c h n ol ogies an d Immunomic Therapeutics, Inc., a next-generation vaccine company. Bob Rager, a member of ITI s Business Advisory Board and early backer of ITI, is founding President of Practical Memory Institute (PMI). He has been principal investigator for many small business innovation research (SBIR) grants from the National Institutes of Health for PMI s memoryzine.com memory maintenance and fitness web site. He is currently guiding ITI s SBIR grant efforts in a peanut allergy vaccine. About Immunomic Therapeutics Immunomic Therapeutics, Inc. (ITI) is a biotechnology company developing next generation vaccines. The Company was formed to commercialize LAMP Vaccine Technology, a novel approach to nucleic acid or DNA vaccines. LAMP (Lysosome-Associated Membrane Protein) was found to greatly enhance the immune response to DNA vaccines by Dr. J. Thomas August, M.D., Distinguished Professor at Johns Hopkins University. ITI has used the LAMP Technology to design new vaccines including immunotherapy for different types of allergy, including hay fever caused by Japanese red cedar pollen. Copyright 2011, Immunomic Therapeutics, Inc. rights reserved. All Kitayama Japan cedar, Kyoto-shi, Kyoto --- Image by YASUO MUROTA/amanaimages/Corbis

Japanese Red Cedar: A Beloved Tree Becomes A National Health Nightmare Since ancient times, Japanese red cedar (Cryptomeria japonica) has been one of Japan s most venerated trees.

5 Japanese Red Cedar: A Beloved Tree Becomes A National Health Nightmare Since ancient times, Japanese red cedar (Cryptomeria japonica) has been one of Japan s most venerated trees. The Japanese call the red cedar tree Sugi ( ). They are part of Japan s cultural heritage and recognized as the country s national tree. Nothing symbolizes the Japanese landscape more than Mount Fuji covered by snow and resplendent Sugi on the adjacent mountainsides. Beginning in the ninth century, temples in and around the cedar mountain regions were built of this versatile hardwood. Many are still in service today.

Perhaps unknowingly and certainly unexpectedly, all this beauty came with an unwelcome price. Cryptomeria japonica, like all trees in the cedar family, depends on wind-borne pollination.

6 Perhaps unknowingly and certainly unexpectedly, all this beauty came with an unwelcome price. Cryptomeria japonica, like all trees in the cedar family, depends on wind-borne pollination. Each spring, the trees develop so many male, pollen-bearing cones that the trees take on their red hue. When the time is right, the cones burst open and release massive amounts of pollen. One estimate has the trees producing 2 kilograms of pollen per square meter of forest! To further compound the problem, cedar is well known to allergists as one of the most potent allergens in nature. While millions of trees were planted with the intent of harvest for lumber, the demand for these trees never arrived. The trees were allowed to grow and mature; in the late 70s and early 80s, the cedar forests began to reach full maturity. The result was the perfect pollen storm.

When February arrives and the cedar trees begin to bloom, it is not uncommon for the uninformed to mistake the springtime cedar pollen cloud for a forest fire or, by some visitors to Japan, as smog.

8 When February arrives and the cedar trees begin to bloom, it is not uncommon for the uninformed to mistake the springtime cedar pollen cloud for a forest fire or, by some visitors to Japan, as smog. Common attire for those venturing outdoors includes face mask and glasses to minimize the exposure to the pollen. The allergy, known as kafunshō, now affects over 35 million Japanese and their pets. Remarkably, cedar pollen is now more reactive in dogs than fleas!

So what are the Japanese to do? They cannot just cut the venerable trees down. Not only are the forests very large, they are generally not on public lands.

10 So what are the Japanese to do? They cannot just cut the venerable trees down. Not only are the forests very large, they are generally not on public lands. In addition, they have sentimental value to the Japanese people who are reluctant to discard a tree planted by a father or grandfather. Control of pollen levels seems an impossibility as traditional allergy treatments - and even new ones - are falling far short of a solution. A new, more effective solution is desperately needed as the problem continues to grow. During the pollen season, newspapers continuously report the pollen count. Surgical facemasks and protective glasses populate store shelves and new products like pollen monitoring devices for indoors and outside are continuously introduced all in an effort to deal with the annual exposure to the cedar pollen clouds.

The Biology of Japanese Red Cedar Pollen: An Up-Close View The cause of the cedar pollen allergy is, of course, the result of inhalation of the pollen grains of Japanese red cedar.

13 The Biology of Japanese Red Cedar Pollen: An Up-Close View The cause of the cedar pollen allergy is, of course, the result of inhalation of the pollen grains of Japanese red cedar. A single pollen grain of Cryptomeria japonica is shown to the right. A scanning electron microscope shows the pollen to be covered with thousands of microbodies plant physiologists call Ubisch bodies. These microbodies serve two functions. They help the pollen adhere to the female cone so that pollination can take place and they contain an enzyme that helps the pollen germinate the egg cell in the female cone.

The impact of this beautiful pollen on the human immune system can be dramatic, causing burning eyes, itchy skin and a runny nose as a result of a strong allergic response.

14 The impact of this beautiful pollen on the human immune system can be dramatic, causing burning eyes, itchy skin and a runny nose as a result of a strong allergic response. Two proteins are primarily responsible for causing the allergy: Cry J1, which is found on the outside of the pollen grain and Cry J2, which is contained within the pollen grain. Japanese cedar pollen can attack the immune system with a one-two punch. The Cry J1, containing Ubisch bodies, are very tiny and can penetrate deep into the lungs. It is this feature that may well be responsible for the link of cedar allergy to asthma and lung inflammation. The second hit comes as the pollen grains naturally explode upon contact with nasal fluids, releasing large amounts of Cry J2. The end result is 35 million Japanese with severe hay fever and the number is growing every year.

Images by Martin Oeggerli Award-Winning Scientific Artist, Martin Oeggerli photographed the images seen on these pages using a scanning electron microscope.

16 Images by Martin Oeggerli Award-Winning Scientific Artist, Martin Oeggerli photographed the images seen on these pages using a scanning electron microscope. His brilliant work has been featured in publications such as the National Geographic magazine and has won numerous competitions and awards. His work can be found on the Internet at

Allergy Immunotherapy A Potential Solution to a Growing Problem For those who suffer from hay fever, the Mast cell (shown on the left) is an unwelcome passenger in the immune system.

19 Allergy Immunotherapy A Potential Solution to a Growing Problem For those who suffer from hay fever, the Mast cell (shown on the left) is an unwelcome passenger in the immune system. It carries with it vesicles filled with histamine one of the main causes of the symptoms we associate with allergy. These cells become covered with a special type of antibody that is produced by an allergy response called IgE. When these cells encounter the pollen and it binds to the IgE, the cells are signaled to release massive amounts of histamine and with it come the watery eyes and runny nose. Medical research is working to provide a solution. One possible course of therapy is to use a vaccine to re-educate the immune system. It may be possible to teach your body to react to pollen proteins like they are a bacteria or virus protein and make the right kind of antibodies know as IgG. It is hoped that by making IgG rather than IgE, the allergic reaction will go away.

21 One new approach to solve the problem is using a vaccine made from DNA rather than from cedar pollen. In this case, the protein that causes the allergy is converted to the genetic code and is safely designed into a vaccine formulation that lets your own cells do all the work. Your immune cells make the protein inside the cell and help the immune system make IgG against the pollen rather than the offending IgE. It is hoped that in this way, the immune system can re-learn how to view pollen proteins and do it in a very safe way. This approach has been tested in mice in the laboratory with Japanese cedar pollen. The mice will make the right antibody IgG whether they receive the JRC vaccine before they are exposed to pollen or after they become allergic to cedar pollen. A very encouraging result!

The Sugi tree is majestic and beautiful. The wonderful cedar fragrance and brightly colored wood are treasured in homes around the world, and no place more than in Japan.

22 The Sugi tree is majestic and beautiful. The wonderful cedar fragrance and brightly colored wood are treasured in homes around the world, and no place more than in Japan. It is now up to the researchers in the biotechnology community to solve the emerging problem of Japanese red cedar hay fever so these trees can be cherished and admired for years to come.

24 About JRC-LAMP-vax Dr. Teri Heiland, VP of R&D, and many others have contributed to the clinical development of our lead product, JRC-LAMP-vax, an immunotherapeutic vaccine for the treatment of hay fever due to cedar pollen. Led by the efforts of Dr. Bruce Mackler, VP of Regulatory Affairs, the Company has initiated all of the preclinical activities necessary to start the study for our lead product JRC-LAMP-vax, a therapeutic SUGI allergy vaccine. LAMP vaccine technology is not limited to allergies.this very attractive market represents a major opportunity for ITI--not only to enter a multibillion dollar market with our lead product, but also to validate the LAMP Technology Platform for other allergy applications, including food allergies, but also for infectious diseases and cancer.

Allergy overload. Nip those springtime allergies in the bud

Allergy overload. Nip those springtime allergies in the bud Y Name: VIBE ACTIVITIES E A R Issue 199 Years Healthy Vibe Healthy Body Allergy Overload page 26 Allergy overload Nip those springtime allergies in the bud W inter s over... the jumpers and trackies go