Amyloidosis is caused by the accumulation of misfolded proteins in tissues and organs of the body. There are three main types of amyloidosis, each of which have different underlying pathologies.
Primary or AL amyloidosis
Primary amyloidosis is the most common form of the condition. This disease is associated with multiple myeloma. In multiple myeloma, the plasma cells in the bone marrow that form an important part of the immune system are affected by cancer. These plasma cells that usually produce antibodies, become dysfunctional and produce abnormal light chain immunoglobulins. The conditions is named after these amyloid light (AL) chains.
The organs and tissues commonly affected by AL amyloidosis include the heart, kidneys, nervous system, and gastrointestinal tract. The treatments used in primary amyloidosis are the same as those used to treat multiple myeloma and include chemotherapy, corticosteroids and proteasome inhibitors.
The aim of chemotherapy is to suppress the bone marrow plasma cells and prevent production of the amyloid protein. The most commonly prescribed drug regimen includes melphalan and dexamethasone, a well tolerated and effective combination that is associated with a rapid response time.
An agent called bortezomib, one of a relatively new class of drugs called the proteasome inhibitors, has been shown to be effective in the treatment of primary amyloidosis and examples of the corticosteroid medications used include lenalidomide and thalidomide.
These treatments are all aimed at slowing disease progression and prolonging survival, but none can provide a cure. However, research has now started to focus on the effects of autologous stem cell transplantation in combination with high-dose chemotherapy and so far, the results seem to be promising.
Secondary amyloidosis or AA amyloidosis
Secondary amyloidosis is usually associated with conditions of chronic inflammation such as rheumatoid arthritis or inflammatory bowel syndrome. Typically, the deposited protein is the acute phase protein serum amyloid A. Medical or surgical therapy of the underlying condition can be helpful in preventing the progression of this amyloid. For example, an antibiotic may be administered in the case of infection or an anti-inflammatory agent in the case of arthritis.
This rare form of amyloidosis is caused by inherited mutations in the genes that make the proteins that form fibrils. The main protein involved is the thyroid hormone-binding protein transthyretin. In most cases, the site of transthyretin production is the liver and liver transplant is an effective therapy. Two new agents called diflunisal and tafamidis are being investigated for their effectiveness in stabilizing the transthyretin and preventing it from depositing in organs.
This form of amyloidosis is inherited in an autosomal dominant fashion, meaning that every child born to an affected parent has a 50% chance of inheriting the defective gene that causes the condition.
Reviewed by Sally Robertson, BSc