Metabolic Disorders

Scientists in the Metabolic Disease Biology Area are looking for novel treatments for abnormalities in metabolism, or the totality of the chemical reactions that occur in living organisms to maintain life.

Examples are:

• diabetes (disordered carbohydrate metabolism),
• dyslipidaemia (disordered fat metabolism),
• anaemia (shortage of red blood cells or low haemoglobin), and
• osteoporosis (loss of bone minerals).

Cardiovascular disease is often grouped with metabolic disorders because of its association with diabetes and dyslipidaemia.

Diabetes mellitus is marked by the body’s inability to utilise glucose normally. Maturity onset (type 2) diabetes is associated with modern diets containing highly refined carbohydrates, obesity and lack of exercise. Nearly 150 million people worldwide suffer type 2 diabetes and experts predict that number will double to 300 million by 2025. Roche’s potential novel treatments target five different mechanisms of action.

R1583 (BIM 51077, licensed from Ipsen) is a long-acting glucagon-like peptide-1 (GLP-1) analogue, with potential for weekly or longer administration intervals. R1583 may enter phase III clinical trials in 2008.

R1579, a dipeptidyl peptidase IV (DPP-IV) inhibitor, is an enzyme that breaks down GLP-1, a hormone involved in blood sugar regulation; phase II clinical testing began in 2007. Additional candidate molecules include R1439 (aleglitazar) in phase II; and R7201 (co-development by Roche and Chugai) and R1511, both in phase I. These compounds address three different potential glucose regulation targets.

Low levels of high-density lipoprotein cholesterol (HDLC), or “good” cholesterol, are associated with increased risk of cardiovascular disease. R1658, licensed from Japan Tobacco and currently in phase III clinical trials, which raises levels of HDLC by inhibiting cholesteryl ester transfer protein (CETP) activity.