Principles Of Therapy

Most of the current therapies in AL and other amyloi-doses are targeted toward the amyloidogenic precursor. The underlying principle is that deposition/resorption of amyloid is a dynamic process. Reduction in precursors or inhibition of amyloid formation will therefore shift the balance toward regression of deposits. A greater degree of reduction in precursors may lead to more durable responses. As the precursors themselves may be responsible for organ dysfunction, this approach may also help preserve organ function.

For example, therapies targeted to the underlying plasma cell clone may lead to reduction in amyloido-genic light chains, and thereby improved organ func-tion.1 Improvement in dialysis-related Ap-2 microglob-ulin can occur with renal transplantation to reduce the levels of serum p-2 microglobulin. In patients with ATTR, liver transplantation has been pursued to provide a source of normal TTR from the transplanted liver. Durable regressions have been observed in several patients in whom liver transplantation was done before the development of severe neuropathy or cardiomy-opathy.33 Patients who receive such transplants late in the disease course, however, can show disease progression due to the deposition of wild type TTR in the heart that already has a nidus of mutant TTR.

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