Treatment and prevention of the amyloidoses: can the lessons learned be applied to sporadic inclusion-body myositis?
The amyloid fibril represents a final common pathologic pathway for a variety of human proteins, all of which have a propensity to misfold. Each seems to require a predisposing event to realize its fibrillogenic potential. It may be mutation, inappropriate or incomplete cleavage, overproduction, or the availability of a template for misfolding. Therapies have been based on decreasing the stimulus (inflammation in the case of AA) reducing the number of producing cells (AL) and a variety of approaches to removing the extracellular aggregates. Sporadic inclusion-body myositis (sIBM), while physically resembling the extracellular amyloidoses, is an intracellular disease, hence imposes the additional requirement of developing a therapy that can access and function inside the affected or potentially affected, cell. Current approaches to the treatment of other forms of amyloidosis are discussed in the context of their applicability, or lack thereof, to sIBM.
Buxbaum
Joel N
JN
Department of Molecular and Experimental Medicine, The Keck Autoimmune Disease Center, The Scripps Research Institute, La Jolla, CA, USA. jbux@scripps.edu
D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000686:Amyloidosis / Q000145:classification / Q000209:etiology / Q000517:prevention & control / Q000628:therapy*; D000818:Animals; D002986:Clinical Trials as Topic; D015195:Drug Design; D004660:Encephalitis / Q000209:etiology; D006801:Humans; D007114:Immunization / Q000009:adverse effects; D007116:Immunization, Passive; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D018979:Myositis, Inclusion Body / Q000517:prevention & control / Q000628:therapy*; D011228:Prealbumin / Q000378:metabolism; D017510:Protein Folding
D000682:Amyloid; D016229:Amyloid beta-Peptides; D011228:Prealbumin; C076571:transthyretin-related amyloid fibril protein, human