Amyloidosis is a group of rare, serious diseases characterized by the buildup of abnormal proteins, known as amyloid fibrils, in various organs and tissues. These misfolded proteins become insoluble and deposit outside of cells, disrupting the normal function of affected organs, such as the heart, kidneys, liver, or nervous system. The resulting damage leads to varied and severe symptoms.
While a complete cure is generally not achievable for most types of amyloidosis, treatments have advanced significantly. Modern therapy aims to halt the production of the toxic precursor protein, allowing existing deposits to stabilize or slowly clear, leading to a state of deep remission. This management has transformed the prognosis to one of long-term disease control and improved organ function.
Defining the Major Types of Amyloidosis
Treatment strategies depend entirely upon identifying the specific type of protein that is misfolding and depositing as amyloid. Three main systemic types account for the majority of clinically relevant cases, each originating from a different precursor protein. The most common form is AL amyloidosis, caused by the overproduction of abnormal immunoglobulin light chain proteins by plasma cells in the bone marrow. These light chains deposit most frequently in the heart and kidneys, often leading to organ failure.
A second type, AA amyloidosis, is considered secondary because it results from an underlying chronic inflammatory condition, such as rheumatoid arthritis or inflammatory bowel disease. The amyloid fibrils are fragments of the serum A protein, which is chronically elevated due to persistent inflammation. AA amyloidosis typically targets the kidneys, liver, and spleen, and its progression is tied directly to the activity of the primary inflammatory disease.
The third major type, ATTR amyloidosis, is caused by the transthyretin (TTR) protein, primarily made in the liver. This form is divided into two subtypes: hereditary (hATTR), where a gene mutation causes unstable TTR production, and wild-type (ATTRwt), where the normal TTR protein misfolds with advancing age. Both forms frequently cause significant damage to the heart, known as cardiomyopathy, and the nerves.
The Distinction Between Cure and Remission
It is important to distinguish between a “cure” and “remission,” as remission is the achievable standard for treatment success in amyloidosis. A true cure remains rare because the capacity for the precursor protein to be produced is usually not completely eliminated.
Remission means the disease-causing process is under control and signs or symptoms have disappeared. The primary goal is to achieve deep remission by completely stopping the production of the new amyloid-forming protein. This cessation allows the body’s natural mechanisms to slowly reabsorb or stabilize existing amyloid deposits over time, leading to improved organ function. Successful treatment is measured by organ stability and the absence of detectable new protein production.
Primary Treatment Approaches for Amyloidosis
Therapies for amyloidosis are highly personalized and focus on eliminating the source of the misfolded protein, as the underlying cause dictates the treatment.
AL Amyloidosis Treatment
For AL amyloidosis, treatment aims at destroying the abnormal plasma cells in the bone marrow that produce the toxic light chains. This is accomplished using chemotherapy regimens and targeted immunotherapies that selectively kill the abnormal cells. For eligible patients, high-dose chemotherapy followed by an autologous stem cell transplant can induce a deep, long-lasting remission.
ATTR Amyloidosis Treatment
Treatment for ATTR amyloidosis focuses on the stability and production of the TTR protein. Novel targeted therapies are used either to stabilize the TTR protein, preventing it from misfolding, or to silence the gene responsible for its production. Stabilizers like Tafamidis bind directly to the TTR protein to keep its structure intact. Gene silencers, such as Patisiran or Vutrisiran, interfere with the messenger RNA, significantly reducing the amount of TTR protein the liver produces.
AA Amyloidosis Treatment
The treatment strategy for AA amyloidosis centers on managing the underlying chronic inflammatory disease that drives the production of the precursor protein. By effectively controlling conditions like rheumatoid arthritis or familial Mediterranean fever with anti-inflammatory medications, the levels of the serum A protein drop. This cessation of new amyloid fibrils often leads to a favorable outcome and can allow for the gradual reversal of amyloid deposits, particularly in the kidneys.
In addition to source-directed therapies, supportive care is important for managing the damage already done to organs. This includes medications to manage heart failure symptoms, such as diuretics, or, in advanced cases of kidney involvement, dialysis or an organ transplant. While supportive care alleviates symptoms and prolongs life, it must be paired with source-directed treatment as it does not address the fundamental disease mechanism.
Long-Term Monitoring and Prognosis
After initial treatment, patients enter long-term surveillance to confirm that remission is maintained and to track the recovery of affected organs. Ongoing monitoring uses specific blood tests, such as serum free light chain assays for AL amyloidosis, to ensure the precursor protein level remains suppressed. Cardiac imaging, including echocardiograms and magnetic resonance imaging (MRI), is routinely used to assess the amyloid burden in the heart and track improvements in function.
Blood biomarkers that reflect organ damage, such as cardiac troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP), are monitored closely. Their levels are strongly linked to the extent of organ damage and the patient’s overall prognosis. A significant factor influencing the long-term outlook is the extent of organ damage at diagnosis, especially cardiac involvement, which is often staged using these biomarkers. Patients diagnosed earlier, before extensive organ damage occurs, typically have a better prognosis and a higher likelihood of achieving long-term survival and stability.