GROUNDBREAKING SCIENCE
Unfolding The Answers

Experiments with mice by UT's Alan Solomon and colleagues showed that a monoclonal antibody could be made to remove amyloid fibrils.

Diseases stemming from deposits of abnormally folded proteins could be the most serious medical problem facing society in the 21st century. So says Alan Solomon, UT professor of medicine and American Cancer Society clinical research professor.

Schooled in the chemistry of proteins, Solomon knows the tragic consequences of proteins that fail to fold along their normal pathways. Many of the devastating diseases caused by misfolded proteins affect the elderly. No effective treatments are available for these diseases, which include Alzheimer's disease, diabetes, and rheumatoid arthritis.

This heart from a patient with primary amyloidosis is enlarged to more than five times the size of the normal organ as a result of extensive amyloid deposition.

One of the most common and deadly of protein-misfolding disorders is amyloidosis. This pathologic process involves the deposition of any one of at least 24 different proteins as amyloid fibrils in the body.

While attending a national amyloid meeting in 1995, it occurred to Solomon that the body might not recognize the fibrils as being foreign tissue. He decided to test whether fibrils obtained from human tissue could be eliminated by mice. Experiments in Solomon's lab showed mice developed antibodies that eliminated the human amyloid. A monoclonal antibody created in Solomon's lab dramatically hastened removal of the amyloid.

"It got rid of the human material five times faster, even before the mice could mount an immune response," Solomon says. However, his appeal to drug companies for help in developing this antibody in a form that could be tested in patients proved futile.

Fortunately, Solomon's appeal to a new National Cancer Institute program called RAID (Rapid Access to Interval Development) brought positive results. The RAID program is designed to translate into clinical practice those promising discoveries that often seem too expensive or risky for commercial development.

In 1998 RAID agreed to create a humanized form of the antibody. In June 2002 RAID decided to produce enough of the antibody for a clinical trial. Aging baby boomers at risk of developing amyloidosis may someday be able to knock out the disease, thanks to research conducted in Knoxville.

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