The Musculoskeletal Diseases DA consists of two fully integrated programs, Bone & Cartilage and Muscle. Novartis has a long history in treatment of disorders of bone metabolism, such as osteoporosis (Miacalcin) and Paget’s disease (Miacalcin, Aredia, Aclasta). The new area, Muscle Disease, will conduct research in muscle atrophy and sarcopenia.
 

Bone & Cartilage
 

Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone architecture, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis continues to be significantly under-diagnosed and untreated. Of the 96 million osteoporosis patients worldwide only about 10 million are currently treated.
 

Our aim at NIBR is to change bone metabolism towards a positive bone balance. This can be achieved by inhibition of resorption, where our cathepsin K inhibitor was the first shown to increase bone mineral density in postmenopausal osteoporosis. Stimulation of bone formation represents the main effort of current research projects. Discovery of bone anabolic drugs is key to those patients that already have fractures and low bone mass that needs strengthening.
 

Muscle
 

Muscle mass and performance is important not only for daily activity but also for metabolism. Muscle decreases with age and this loss is called sarcopenia. Muscle atrophy is, however, also a clinically significant co-morbidity seen in a variety of conditions, such as chronic obstructive pulmonary disease, liver disease, burns or cachexia in cancer, congestive heart failure and AIDS. Since only one pharmacologic agent, growth hormone, is approved for the treatment of muscle atrophy in AIDS cachexia, there exists a large unmet medical need.
 

The goal of the program is to understand the cell signals mediating skeletal muscle atrophy and hypertrophy and the mechanism for loss of muscle during aging. Targets thereby identified will allow us to develop pharmacologic agents for the treatment of muscle atrophy, sarcopenia, and muscular dystrophy.

The Musculoskeletal DA is headed by Brian Richardson and is located in Basel (Switzerland) and Cambridge (USA).

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Gasser JA, Green JR, Shen V, Ingold P, Rebmann A, Bhatnagar AS, Evans DB. (2006). A single, intravenous administration of zoledronic acid prevents the bone loss and reduction of mechanical properties induced by aromatase inhibition or surgical ovariectomy in rats. Bone 2006 Jul 14; [Epub ahead of print].
 

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Esser R, Berry C, Du Z, Dawson J, Fox A, Fujimoto RA, Haston W, Kimble EF, Koehler J, Peppard J, Quadros E, Quintavalla J, Toscano K, Urban L, van Duzer J, Zhang X, Zhou S, Marshall PJ (2005). Preclinical pharmacology of lumiracoxib: a novel selective inhibitor of cyclooxygenase-2. Br J Pharmacol. 144(4):538-50.
 

Latres E, Amini AR, Amini AA, Griffiths J, Martin FJ, Wei Y, Lin HC, Yancopoulos GD, Glass DJ (2005) IGF-1 inversely regulates atrophy-induced genes via the PI3K/Akt/mTOR pathway. J Biol. Chem, 280 (4): 2737-2744

Miacalcic®/Miacalcin® (salmon calcitonin) inhibits the activity of bone-resorbing cells and thereby improves bone strength in osteoporosis and is effective in Paget's disease or hypercalcaemia patients.

Prexige® (lumiracoxib) against osteoarthritis belongs to the class of drugs known as COX-2 inhibitors, which are non-steroidal anti-inflammatory drugs. It has an excellent GI safety profile. Prexige already received approval in the EU and several other markets.

Aclasta®/Reclast® (zoledronic acid) has shown superior efficacy in Phase III studies in Paget’s disease, a condition marked by abnormal bone growth. It has received approval in EU and an approvable letter by FDA.

Aclasta®/Reclast® (zoledronic acid) has the potential to become the gold standard in treating osteoporosis. Phase III studies of once-yearly 5 mg infusions indicated a 70% reduction of new vertebral fractures over 3 years and significant reductions of non-vertrebal fractures including hip. It is expected to provide unsurpassed compliance and excellent long-term bone protection.