Aeolus Pipeline Initiative: Autoimmune Disorders

Third party scientific collaboration group to be selected in early fourth quarter 2005.
Arthritis
The word "arthritis" is often used to refer to all rheumatic diseases. However, the word literally means joint inflammation; that is, swelling, redness, heat and pain caused by tissue injury or disease in the joint. The many different kinds of arthritis comprise just a portion of the rheumatic diseases. Some rheumatic diseases are described as connective tissue diseases because they affect the body’s connective tissue--the supporting framework of the body and its internal organs. Others are known as autoimmune diseases because they are caused by a problem in which the immune system harms the body’s own healthy tissues. Examples of some rheumatic diseases are:

• Osteoarthritis
• Rheumatoid arthritis
• Fibromyalgia
• Systemic lupus erythematosus
• Scleroderma
• Juvenile rheumatoid arthritis
• Ankylosing spondylitis
• Gout

Millions of Americans suffer from arthritic conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gout. These disorders are characterized by joint pain in the extremities. Many other inflammatory diseases affect the body’s soft tissues, including tendonitis and bursitis. The most common type of arthritis is osteoarthritis, affecting more than 16 million Americans. This degenerative joint disease is common in people over 65, but may appear decades earlier. Rheumatoid arthritis, which affects 2.5 million Americans, can strike at any age, but usually appears between ages 20 and 50.

An estimated 40 million people in the United States have arthritis or other rheumatic conditions. By the year 2020, this number is expected to reach 59 million. Rheumatic diseases are the leading cause of disability among adults age 65 and older.

Manganese porphyrins have been shown to have efficacy in an ex vivo model of osteoarthritis (Arthritis & Rheumatism, 50:1, 123, 2004). Compression injury induced apoptosis in cartilage disks from 22-month-old bovines, a model of arthritic damage, evidenced a reduction in the percentage of apoptotic cells induced by injury in a dose-dependent manner using AEOL 10112 (complete inhibition with 2.5 µM), while a-tocopherol, and enzymatic antioxidant, had no effect. These data suggest that the Aeolus catalytic antioxidants may be effective in slowing the progressive destruction of joint tissue in arthritis.

Ulcerative Colitis
Ulcerative colitis is a chronic inflammation of the large intestine (colon). The colon is the part of the digestive system where waste material is stored. The rectum is the end of the colon adjacent to the anus. In patients with ulcerative colitis, ulcers and inflammation of the inner lining of the colon lead to symptoms of abdominal pain, diarrhea, and rectal bleeding. Ulcerative colitis is closely related to another condition of inflammation of the intestines called Crohn’s disease. Together, they are frequently referred to as inflammatory bowel disease, or IBD. Ulcerative colitis and Crohn’s diseases are chronic conditions that can last years to decades. They affect approximately 500,000 to 2 million people in the United States. Men and women are affected equally. They most commonly begin during adolescence and early adulthood, but they also can begin during childhood and later in life. It is found worldwide, but is most common in the United States, England, and northern Europe. It is especially common in people of Jewish descent. Ulcerative colitis is rarely seen in Eastern Europe, Asia, and South America, and is rare in the black population.

The causes of ulcerative colitis and Crohn’s disease are unknown. To date, there has been no convincing evidence that these two diseases are caused by infection. Neither disease is contagious. Ulcerative colitis and Crohn’s disease are caused by abnormal activation of the immune system in the intestines. In patients with Crohn’s disease and ulcerative colitis, the immune system is abnormally and chronically activated in the absence of any known invader. The continued abnormal activation of the immune systems causes chronic inflammation and ulceration. The susceptibility to abnormal activation of the immune system is genetically inherited. First degree relatives (brothers, sisters, children and parents) of patients with IBD are thus more likely to develop these diseases.

A compound from the AEOL 112 series of manganoporphyrins has been shown to have efficacy in a rat model of IBD.