Amyloidosis occurs when a build up of the protein, amyloid, collects in clusters in the tissues and organs, impeding their healthy function. Amyloidosis is a serious health problem that can lead to life-threatening organ failure (i.e, heart disease, kidney damage, digestive disorders, bone marrow destruction, and nerve disorders) if left untreated. There are three main types of amyloidosis: primary amyloid, secondary amyloid, and familial or hereditary amyloid. Amyloidosis causes several symptoms, including:
- Purpura (purple bags or spots)around the eyes
- Swelling of the legs and ankles
- Shortness of breath
- Numbness or pain in the hand, feet and wrist
- Difficulty swallowing
- Unexpected weight loss
- An enlarged tongue
- Bloody diarrhea or constipation
- An irregular heartbeat
- Skin changes like thickening and easy bruising
Here is a run down of amyloidosis types and treatments for each:
1. Primary Amyloidosis
This is the most common form of amyloidosis. The antibody protein deposited is part of the light chain. Originating in the bone marrow, primary amyloid is a plasma cell disorder. It is treated as a type of bone cancer with chemotherapy. This condition affects about 2,000 persons in the U.S. each year.
2. Secondary Amyloidosis
This secondary type is composed of deposits of the AA protein. This disease appears as inflammatory disease or chronic infection. Inflammatory bowel disorders, an intestinal disorder like familial Mediterranean fever, rheumatoid arthritis and infection of the bone as in osteomyelitis are all variations of the disease. Secondary amyloid is treated with surgery or standard medical treatment of the condition presented.
3. Familial amyloidosis
Also known as hereditary amyloidosis, this is the only type of amyloid that is inherited and it is very rare. It affects a limited number of every ethnic background. It is the result of a gene mutation that causes the protein transthyretin (TTR) to be deformed. This protein is made mostly in the liver and responsible for transporting important nutrients throughout the body. TTR builds up in clusters becoming amyloid deposits that are distributed throughout the body negatively affecting the heart, the kidneys, the digestive system and the nerves, leading to disability or death. If it affects the liver, a liver transplant is a preferred treatment.
4. Chemotherapy for amyloidosis
When amyloidosis presents as plasma cell disorder in the bone marrow, it is treated as osteomyelitis or bone cancer. Treatment for this condition is often chemotherapy used to destroy these deformed cells. The chemotherapy may be introduced intravenously, via a tube under the skin or via a capsule or pill to be swallowed. The chemotherapy drugs could be melphalan (Alkeran) and cyclophosphamide (Cytoxan, Neosar) combined with dexamethasone and prednisone. The therapy is cyclical. The drugs can be taken alone or in combination with other drugs.
5. Targeted therapy for amyloidosis
Targeted therapy focuses on specific proteins or tissues contributing to the development of amyloidosis. The goal is to stop or block the spread of the damage with the following therapies:
- Immunomodulatory drugs such as lenalidomide (Revlimid), thalidomide (Synovir, Thalomid) and pomalidomide (Pomalyst) make up one type of targeted therapy.
- Monoclonal antibodies recognize and attach to a specific protein in the abnormal cells. Drugs in this class include elotuzumab (Empliciti)and daratumumab (Darzalex).
- Proteasome inhibitors are another type of targeted therapy. These drugs target specific enzymes called proteasomes. Proteasomes digest proteins in the cells. Inhibitors: carfilzomib (Kyprolis), bortezomib (Velcade) and ixazomib).
6. Immunotherapy for amyloidosis
Immunotherapy is a cancer therapies designed to stimulate the body’s immune system to better recognize the deformed proteins and fight the amyloidosis, using the following:
- Checkpoint inhibitors work by disrupting the clustered cells’ signals, exposing them to attack by the immune system.
- Vaccines for amyloidosis come in two categories: Prophylactic or preventative vaccines attack viruses. Therapeutic or treatment vaccines stimulate the immune system to attack amyloidosis.
- Cytokines are released by cells naturally and recreated by labs. They generate protein molecules to help regulate and direct the immune system: Interleukin 2 (IL-2) helps the body produce antigen-fighting T-cells and stimulates B-cells to produce more antibodies. Interferon-alpha (IFN-alpha) helps the body generate immune cells designed to attack unhealthy cells.