Amyloidosis is the extracellular deposition of normally soluble autologous
protein in a characteristic abnormal fibrillar form. Systemic
amyloidosis and some local forms are progressive, cause major morbidity, and are often fatal. No treatment specifically causes the resolution of
amyloid deposits, but
therapy that reduces the supply of
amyloid fibril precursor
proteins can improve survival and preserve organ function. Major regression of
amyloid occurs in at least a proportion of such cases, suggesting that the clinical improvement reflects mobilization of
amyloid. The clearest evidence for regression of
amyloid has been obtained in
juvenile rheumatoid arthritis patients with
AA amyloidosis treated with
chlorambucil. This
drug suppresses the acute phase production of
serum amyloid A protein, the precursor of AA
amyloid fibrils, and is associated with remission of
proteinuria and greatly improved survival. In many such patients, scintigraphy with
serum amyloid P component shows major regression of
amyloid over 12 to 36 months and frequently reveals a discrepancy between the local
amyloid load and organ dysfunction. Measurement of target organ function is therefore not an adequate method for monitoring treatment aimed at promoting the resolution of
amyloid. In monoclonal
immunoglobulin light chain (
AL) amyloidosis the aim of treatment is to suppress the underlying B-cell clone and, therefore, production of the
amyloid fibril precursor
protein. This can be difficult to achieve or sustain and, since the prognosis is so poor, many patients die before benefits of
therapy are realized. A recent development has been the introduction of
liver transplantation as treatment for
familial amyloid polyneuropathy caused by
transthyretin gene mutations. This leads to the disappearance of variant
transthyretin from the plasma and halts progression of the neurologic disease. Features of autonomic neuropathy frequently ameliorate, and improvement in peripheral motor nerve function has been recently reported.
Serum amyloid P component scans show regression of associated visceral
amyloidosis. This surgical form of gene therapy holds much promise for patients with
familial amyloid polyneuropathy and has been widely adopted. The only other form of
amyloidosis in which the supply of the fibril precursor
protein can be sharply reduced is beta 2M
amyloidosis in long-term
hemodialysis patients.
Renal transplantation lowers the plasma concentration of beta 2M to normal levels and is associated with rapid improvement of the osteoarticular symptoms. Preliminary observations suggest that the beta 2M
amyloid deposits also can regress in some patients.(ABSTRACT TRUNCATED AT 400 WORDS)