News Archive, 2004

BOSTON BIOMEDICAL RESEARCH INSTITUTE AND WYETH ANNOUNCE LICENSING OF ALZHEIMER’S IMMUNOTHERAPY
GROUND-BREAKING APPROACH ENABLES WYETH AND ELAN TO BROADEN PORTFOLIO IN THE FIGHT TO TREAT ALZHEIMER’S DISEASE

Watertown, Mass.—November 22, 2004 — Boston Biomedical Research Institute (BBRI) has announced that it has entered into an agreement with Wyeth Pharmaceuticals, a division of Wyeth (NYSE: WYE) to license BBRI’s patented technology for immunotherapy to combat Alzheimer’s disease. This agreement will further the Elan and Wyeth collaboration with BBRI on beta amyloid immunotherapy for the treatment of Alzheimer’s disease. The ground-breaking work forming the basis for the patent applications was conducted in the lab of Dr. Vic Raso, a senior scientist at BBRI.

About the announcement, Dr. Charles Emerson, Director of BBRI said, “Dr. Raso’s achievement is a validation of the power of investigator-initiated basic research in the development of innovative cures for devastating diseases. BBRI is dedicated to providing support for investigators like Dr. Raso who are doing innovative work that is not yet supported by conventional funding sources. There is a great need for more public and private support for research such as this at the very frontier of science, where there are no rewards without risk.”

Alzheimer’s disease is the most common cause of dementia, and the fourth leading cause of death in developed countries. It is estimated that more than four million people in the U.S. and between 6 and 7 million in Western Europe currently suffer from Alzheimer’s disease, and its prevalence doubles every five years beyond age 65, up to an incidence of 1:3 in people in their 80’s.

Under the terms of the licensing agreement, Wyeth will pay an up front licensing fee and will pay patent costs for the technology. Additional milestone payments are possible based on the issuance of certain BBRI patent claims, approval of a commercial product covered by issued patent claims, and royalties on that product. Specific terms of the agreement were not disclosed.

About Boston Biomedical Research Institute
BBRI is an independent, not-for-profit institution, dedicated to basic biomedical research to promote the understanding, treatment, and prevention of human diseases, including heart disease, cancer, muscular dystrophy and Alzheimer’s. Areas of research focus on biochemical molecular and cellular mechanisms of muscle contractility and cell movement, cell growth and differentiation, and tissue repair and regeneration.

About Wyeth Pharmaceuticals
Wyeth Pharmaceuticals, a division of Wyeth [NYSE:WYE] is one of the world’s largest research-driven pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and non-prescription medicines that improve the quality of life for people worldwide.

DISCOVERY AT BOSTON BIOMEDICAL RESEARCH INSTITUTE OPENS DOORS TO NEW TREATMENTS FOR MUSCULAR DYSTROPHIES
Watertown, Mass. – December 1, 2004 – This week the Journal of Clinical Investigation (JCI), a top-tier journal that publishes biologically significant findings with clinical relevance will publish the research findings of a team of scientists at the not-for-profit Boston Biomedical Research Institute (BBRI). The discovery holds promise for development of new treatments for a type of congenital muscular dystrophy in which patients have severe muscle weakness beginning in infancy.

Led by Dr. Jeffrey Boone Miller, the team at BBRI is seeking to identify therapies for Congenital Muscular Dystrophy Type 1A, CMD1A, by preventing a type of cell death termed apoptosis, or programmed cell death. Though apoptosis is a normal process that is used to remove damaged cells from the body, an excess of apoptosis, as occurs in some diseases, can cause excessive tissue loss and be deleterious. Preventing such excessive programmed cell death might thus restore the normal balance of cell life and death and ameliorate diseases such as congenital muscular dystrophies.

“Dr. Miller’s discovery of the role of apoptosis in congenital muscular dystrophy highlights the power of basic science and disease model research to reveal new therapeutic approaches for human disease, which is a hallmark of BBRI research,” says BBRI’s director Dr. Charles Emerson.

As a disease model for CMD1A, Dr. Miller’s laboratory is studying mice in which a gene called Lama2 has been made nonfunctional. In their work, Dr. Miller’s group has shown that muscle disease in the Lama2-deficient mice is improved by genetic alterations that inhibit programmed cell death. Specifically, both the growth and the survival of Lama2-deficient mice are greatly improved when apoptosis is inhibited by genetically removing a protein termed Bax, which promotes cell death. These findings provide new insight into the normal function of Lama2 as a signaling protein that instructs muscles that they are healthy and identify Bax as a drug target for the development of pharmacological therapeutics to treat CMD1A muscular dystrophy.

Dr. Miller’s laboratory is now working to screen for Bax drug inhibitors to treat CMD1A in the Lama2-deficient mouse model as well as to determine if additional neuromuscular degenerative diseases, such as Limb-Girdle Muscular Dystrophies, can be ameliorated by targeted alterations of Bax and other Bcl-2 checkpoint proteins. The JCI has been published continuously since 1924, and has been a free access journal since 1996.

For more information, contact: Virginia Sullivan, Associate Director of Institutional Advancement, Boston Biomedical Research Institute: Tel: 617-658-7711, Fax: 617-972-1760, email: sullivan@bbri.org.

DR. ERIC SUNDBERG JOINS TEAM OF SCIENTISTS AT BOSTON BIOMEDICAL RESEARCH INSTITUTE
Watertown, Mass.—June 25, 2004 — Watertown based Boston Biomedical Research Institute has recruited Eric J. Sundberg, Ph.D., to join its faculty of 25 scientists doing discovery research in biochemistry, cell biology and molecular biology to uncover the causes of human disease. Dr. Sundberg’s research focuses on understanding of how proteins of the immune system interact to carry out normal body functions and how these interactions are poisoned by deadly bacterial toxins, leading to immune failure in diseases such as toxic shock syndrome. His research is leading to a new understanding of the structural and chemical principles underlying how proteins interact to control physiological functions in the body and has exciting promise for development of novel immune-based therapies to protect humans from often deadly reactions to toxins as well as to harness the body’s immune system to search out and kill cancer cells. “Dr. Sundberg is an outstanding scientist who is making great strides in increase our understanding the principles of how protein molecules interact to allow cells to communicate with one another to control normal physiological processes in our bodies and well as protect us from pathogens and toxins. Importantly, his work also will help us to understand how breakdowns in protein interactions lead to human disease that will be a basis for the development of new therapies to treat the root causes of theses diseases,” says Dr. Charles P. Emerson, Jr, BBRI’s Director.

Dr. Sundberg was formerly Assistant Professor at the Center for Advanced Research in Biotechnology at the University of Maryland Biotechnology Institute He earned his B.A. in Economics and a B.S. in Biochemistry from the University of Rochester and received a Ph.D. in Biological Sciences from Northwestern University. He was an Arthritis Foundation Fellow, completing his postdoctoral fellowship in the laboratory of Dr. Roy A. Mariuzza at the W.M. Keck Laboratory for Structural Biology at the University of Maryland.

TEAM OF BOSTON SCIENTISTS DETERMINES THE FIRST ATOMIC STRUCTURE OF A PROTEIN PHOSPHATASE BOUND TO A REGULATORY PROTEIN

DISCOVERY OPENS DOORS FOR RATIONAL DRUG DESIGN

Watertown, Mass.—May 25, 2004 — This week the journal Nature will publish the research findings of two teams of scientists at the not-for-profit Boston Biomedical Research Institute (BBRI) who are the first to determine the molecular structure of protein phosphatase 1 (PP1) complexed with a regulatory protein known as MYPT1. PP1 is an enzyme involved in a wide range of biological functions in the human body. Its function is always mediated by other proteins that are called regulatory subunits, of which there exist many. The interaction of these substances was heretofore unknown. The atomic structure reveals for the first time how the action of this important human enzyme is modified by a regulatory subunit in the human body.

Led by Drs. Roberto Dominguez and Terry Tao, the teams at BBRI used a method known as X-ray crystallography, which involves passing intense X-ray beams through crystals of proteins and employing complex mathematical procedures in order to define the exact position in space of each of the thousands of atoms that make up a protein molecule. By determining the structure of a protein, scientists can learn how the protein functions, knowledge that is fundamental to rational drug discovery.

The PP1 complex that has been determined plays a role in the relaxation of smooth muscle, the sort of muscle which forms the internal organs of the human body such as blood vessels and the uterus. This discovery will therefore provide an avenue toward the design of new drugs for the treatment of hypertension, asthma and other diseases.

Drugs targeting phosphatases are expected to result in a $20 billion drug market in the next five years, according to a recent market study by the journal PharmaGenomics. This newly determined structure will greatly aid this emerging area of drug exploration.

“Phosphatases are a vital part of countless biological functions in our bodies,” says Dr. Dominguez, “and the way they work is by forming complexes with regulatory subunits. This is the first time such a complex has been directly visualized, and the new knowledge it brings is not only important for drug discovery, but is of great general importance to basic science.”