Session Title: Inflammation
EFFECTS OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) ON AMYLOID PATHOLOGY IN MUSCLE
T.L. Beckett, R.L. Webb, M.P. Murphy
Inclusion body myositis (IBM) is the most common degenerative muscle disease affecting the elderly population and currently there is no effective treatment. One of the distinguishing characteristics of IBM pathology is the intracellular deposition of the Aβ peptide, a derivative of the amyloid precursor protein (APP). Deposition of Aβ is also a hallmark of Alzheimer's disease (AD), where Aβ plays a key role for its development, although in AD the Aβ is deposited extracellularly. Our lab is interested in mechanisms that are shared between these two diseases. Transgenic mice that overexpress APP in muscle develop inclusion bodies and show a consistent decline in motor function with age (e.g., transgenic mice show a ∼36% decline in wire suspension by 12 months of age, in contrast to a ∼20% decline in WT animals). We have previously reported that a subset of NSAIDs can selectively reduce Aβ42 in vivo, and reduce the risk of AD in humans. If the two diseases are linked, then these compounds will also impede the development of IBM pathology. We treated IBM transgenic mice with 4 different NSAIDs (Naproxen, Ibuprofen, Carprofen and R-Flurbiprofen) at a concentration of 10 mg/kg over a period of 6 months, beginning at the age when the pathology is first detectable (12 months). Motor testing was conducted throughout the length of the study, and tissue were collected for an end point analysis of pathology. These results may lead to new insights into therapies for the treatment of both IBM and AD.