Amyloidosis

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UT Southwestern Medical Center physicians have extensive expertise in diagnosing and treating all types of amyloidosis, a rare and complex disease that involves the buildup of abnormal proteins in tissues and organs.

Bringing together interdisciplinary experts whose goal is to provide patients personalized care to relieve their symptoms and improve their quality of life, UT Southwestern is the only academic medical center in Texas with a National Cancer Institute-designated comprehensive cancer center and multidisciplinary amyloidosis program.

Pioneers in the Diagnosis and Care of Amyloidosis

Amyloidosis (am-uh-loy-doh-sis) is a protein-folding disorder. With this disease, proteins change shape (misfold) and then clump together to form amyloid fibrils. These amyloid fibrils can deposit in organs such as the heart, nerves, gastrointestinal tract, and kidneys. Over time, as the amyloid fibrils build up, tissues and organs may not work as well as they should.

At UT Southwestern, a multidisciplinary group of physicians and scientists led by Justin Grodin, M.D., M.P.H., and Gurbakhash Kaur, M.D., are at the forefront of research, diagnosis, and treatment for various types of amyloidosis.

Our team of cardiologists, oncologists, gastroenterologists, neurologists, pathologists, molecular biologists, nephrologists, physiatrists, geriatricians, and other experts develops a personalized treatment plan for each patient, taking into account the type of amyloidosis, the organs affected, patient genetics, and patient preferences. This helps increase the likelihood that the treatment will be effective while decreasing potential side effects and complications.

Additionally, we have specialized expertise in organ transplantation to treat very rare forms of amyloidosis, such as apolipoprotein A-I (AApoAI), apolipoprotein A-II (AApoAII), gelsolin (AGel), fibrinogen (AFib), and lysozyme (ALys). We also treat localized amyloidosis, a form of the disease that’s limited to one organ, such as the bladder, eye, or skin.

Types of Amyloidosis We Treat

ATTR amyloidosis

In ATTR amyloidosis, the “A” stands for amyloid, and the “TTR” stands for transthyretin, a protein the liver produces that helps carry thyroid hormone and vitamin A throughout the bloodstream to other parts of the body. In ATTR amyloidosis, the TTR protein becomes unstable, breaks apart, and forms amyloid fibrils that deposit in both the heart and nerves.

ATTR deposits in the heart are commonly associated with ATTR deposits in the spinal ligaments, causing a condition called spinal stenosis (narrowing), and in the carpal tunnel (a narrow passageway for nerves in the wrist), causing carpal tunnel syndrome.

ATTR amyloidosis has two types, both of which we have experience treating:

Hereditary (hATTR), which results from inherited genetic mutations in the TTR gene
Wild type (ATTRwt), which typically occurs in men age 80 and older but is being diagnosed more and more in patients, including women, as young as their early 60s

AL amyloidosis

In AL amyloidosis, the “A” stands for amyloid, and the “L” stands for light chain. Light chains are components of antibodies, or immunoglobulins, made by plasma cells in the bone marrow. In AL amyloidosis, a group of plasma cells makes too many light chains, which misfold and clump together to form amyloid fibrils. The fibrils are then deposited in organs.

AL amyloidosis usually affects people from ages 50 to 80 but in rare circumstances does affect younger people. It’s caused by a bone marrow disorder, but it can affect multiple organs.

AL amyloidosis most commonly affects the heart (a cause of cardiac amyloidosis) and kidneys. It can also affect the stomach, large intestine, liver, nerves, and skin. The condition can cause problems with one or more parts of the body.

Amyloidosis and the heart and nerves

Both ATTR and AL amyloidosis can cause cardiac amyloidosis, a condition in which amyloid deposits cause heart muscle tissue to stiffen, preventing the heart from contracting and relaxing normally during heartbeats. When this happens, the heart can’t pump blood efficiently to the body, causing heart failure, arrhythmias (abnormal heart rhythms), and other heart problems. Cardiac amyloidosis can be life-threatening and requires prompt, effective treatment.

Amyloidoses can also lead to neuro-specific issues such as peripheral neuropathy, a disorder caused by damage to the peripheral nervous system, the network of spinal and cranial nerves linked to the brain and the spinal cord. Peripheral neuropathy is the most common neurological complication of systemic amyloidosis (amyloidosis that involves the entire body). It can affect the nerve fibers involved in sensation, muscle control, and involuntary physiologic processes.

At UT Southwestern, our experts also treat other rare amyloidosis types, such as:

ALECT2, which typically affects the liver and kidneys
AFib, caused by mutations in the fibrinogen alpha chain gene
ALys, caused by mutations in the lysozyme gene
AApoA4
AH (heavy chain amyloidosis)

Symptoms of Amyloidosis

AL and ATTR amyloidosis can cause symptoms such as:

Frequent urination during the night
Weak nails
Enlarged tongue (specific to AL amyloidosis)
Purplish color around the eyes (specific to AL amyloidosis)
Carpal tunnel syndrome
Narrowing of the spine (spinal stenosis)
Spontaneous tendon rupture (specific to ATTR amyloidosis)

Cardiac-specific symptoms of amyloidosis

Signs of cardiac amyloidosis may include:

Discomfort in the chest due to the lack of oxygen-rich blood (angina)
Heart palpitations
Reduced ability to exercise
Fatigue
Shortness of breath when lying down
Swelling of the abdomen, legs, or ankles

Neuro-specific symptoms of amyloidosis

Symptoms of amyloid neuropathy may include:

Painful pins and needles sensation, usually felt in the legs, arms, or feet
Difficulty balancing
Nausea
Vomiting
Bowel issues (diarrhea or constipation)
Loss of bladder control
Sexual dysfunction

Diagnosing Amyloidosis

At UT Southwestern, we begin with a thorough evaluation that includes a:

Discussion of symptoms
Review of personal and family medical history
Physical exam

We often recommend one or more additional tests to confirm the type of amyloid involved, such as:

Blood tests: Checks heart, kidney, and liver function and looks for signs of antibodies (immunoglobulins) and free light chains
Bone marrow biopsy: Removal of a small tissue sample from inside a bone, where blood cells are produced, to evaluate plasma cells
Endomyocardial biopsy: Removal of a small tissue sample to check for amyloid deposits, using a catheter (thin tube) guided to the heart through a vein
Fat pad biopsy: Removal of a small sample of fat tissue from the abdomen to check for amyloid deposits
Magnetic resonance imaging (MRI) scan: Test that uses a large magnet and radio waves to produce detailed images of the organs
24-hour urine collection: Checks for excess protein

Cardiac-specific diagnosis

Diagnostic tests for cardiac amyloidosis may include:

Chest or abdomen computed tomography (CT) scan: Technology that uses a thin beam of X-ray to generate cross-sectional images of organs
Cardiac magnetic resonance imaging (MRI) scan: Test that uses a large magnet and radio waves to produce detailed images of the heart to assess its size and shape and to detect the presence of amyloid in the muscle
Coronary angiography: Test that uses contrast dye and X-ray to create pictures of the arteries in the heart
Echocardiography (echo or cardiac ultrasound): Imaging test that uses sound waves to produce a video of the heart to look for thickened muscle and amyloid deposits
Electrocardiogram (ECG or EKG): Records the heart’s electrical activity to check for rhythm problems
Endomyocardial biopsy: Removal of a small tissue sample to check for amyloid deposits, using a catheter (thin tube) guided to the heart through a vein
Nuclear imaging: Scan to check for cardiomyopathy (abnormal heart muscle function) using an injection of a radioactive dye that shows up on images taken by a special camera

Types of nuclear imaging include:

Scintigraphy: Uses tracer amounts of radioactive molecules to create scans of the heart; in some people, this noninvasive test can be used instead of a biopsy to diagnose ATTR amyloidosis.

Neuro-specific diagnosis

To confirm a diagnosis of amyloid neuropathy, our doctors may recommend:

Autonomic testing: Tests that measure how heart rate and blood pressure respond to stimulation
Electromyography and nerve conduction studies: Tests that evaluate the electrical activity of muscles and nerves
Skin biopsy: Removal of a small sample of skin to check the distribution of nerves
Nerve and muscle biopsy: Removal of small samples to check for amyloid deposits

Treatment for Amyloidosis

AL amyloidosis treatments offer hope, potential cure

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AL amyloidosis

Treatment of AL amyloidosis can help reduce symptoms, reduce heart failure-related hospitalization, and improve the length and quality of life.

Treatment plans are tailored to each patient and are based upon disease progression and seriousness of the patient’s organ, tissue, and nerve involvement. Currently, treatment options are focused on reducing the production of light chain protein from the bone marrow; however, newer treatments are in clinical development, such as CAEL-101, a novel antibody that may be able to clear the deposited protein in various organs and promote quicker recovery.

Treatment plans include both supportive treatment and source treatment.

Supportive Treatment

Supportive treatment is helpful for various symptoms, including cardiac and kidney problems, and can make a significant improvement in a patient’s quality of life. Examples include:

Cardiac medication
Preserving kidney function
Symptomatic treatment of neuropathy
Geriatric assessments
Psychological support

Reversing any damage to the organs and other parts of the body is difficult to achieve. However, if treatment begins during the early onset of clinical symptoms, the overall success rate is higher, so early detection is essential.

Source Treatment

A bone marrow transplant is often considered the preferred treatment for AL because it can provide long-term control of the underlying disease. However, only a minority of AL patients are eligible.

For the majority of AL amyloidosis patients, other chemotherapy-based treatments are considered. These treatment regimens are tailored for each patient based on organ function, symptoms, and preferences.

Patients with AL amyloidosis have benefited from the development of new drugs for myeloma, many of which work effectively on the plasma cells that cause AL amyloidosis. Often, drug combinations are more effective than single drugs in attacking the abnormal plasma cells. Dosage is tailored to each patient. Categories of drugs that may be used include:

Traditional chemotherapy drugs: Melphalan, Cyclophosphamide (Cytoxan™), Bendamustine (Treanda™)
Proteasome inhibitors: Bortezomib (Velcade™), MLN9708 (Ixazomib™), Carfilzomib (Kyprolis™)
Immunomodulators: Thalidomide (Thalidomid™), Lenalidomide (Revlimid™), Pomalidomide (Pomalyst™).
Monoclonal antibodies: daratumumab (Darzalex)

Some of these drugs are still considered investigational for AL amyloidosis and should not be used outside of a sponsored clinical trial. Most of them are given with a steroid, such as dexamethasone, which seems to increase their effectiveness.

Advances for ATTR amyloidosis patients

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ATTR amyloidosis

Treatment for ATTR can be divided into three categories:

TTR silencers, such as patisiran or inotersen, which reduce TTR production in the liver
TTR stabilizers, such as tafamidis, which stabilize the TTR protein structure and prevent it from breaking up and forming amyloid fibrils
ATTR fibril disruptors, which remove existing amyloid deposits from the heart and other tissues

At UT Southwestern, our patients have access to leading-edge therapies through our experienced physicians. In 2018, the FDA approved two medications for hATTR amyloid polyneuropathy: patisiran (an siRNA) and inotersen (an antisense oligonucleotide). In May 2019, the FDA approved tafamidis for hATTR or ATTRwt cardiomyopathy.

To treat heart failure in people with ATTR amyloidosis, our physicians also use loop diuretics such as furosemide. Depending on each patient’s symptoms, we might also prescribe other heart failure medications, which can help the heart pump more blood to the body by relaxing blood vessels and reducing blood pressure. We monitor these patients very closely for any side effects.

Several new medications are available through clinical trials to treat ATTR amyloidosis. At UT Southwestern, eligible patients have access to these promising and advanced treatments.

Cardiac-specific diagnosis

For patients with cardiac amyloidosis, UT Southwestern physicians focus on managing heart failure and treating the underlying condition that is causing the amyloid deposits.

Because these patients may not tolerate certain medications commonly used in heart failure or other heart conditions, it’s important to have a precise diagnosis for safe, effective treatment.

We may recommend:

Lifestyle changes: Limiting salt intake or making other dietary changes
Water pills (diuretics): Medicine that increases the amount of water and salt removed from the body as urine
Medications to treat atrial fibrillation (irregular heartbeat): Beta-blockers or other medicines
Heart transplant
Implantable cardioverter-defibrillator (AICD) or pacemaker: Electronic devices that monitor and correct an arrhythmia

Amyloidosis Research at UT Southwestern

Through various research initiatives, we seek to advance diagnosis and treatment of all forms of amyloidosis.

Clinical trials

We are active in a variety of amyloidosis research, from translational research to clinical epidemiology. As one of the nation’s leading academic medical centers, UT Southwestern offers clinical studies that aim to improve outcomes of patients with amyloidosis.

Current clinical trials include:

CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of AKCEA-TTR-LRx in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM): To evaluate the efficacy of AKCEA-TTR-LRx compared to placebo for 120 weeks in patients with ATTR-CM receiving available standard of care (SoC)
Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy (ATTRIBUTE-CM): Phase 3 efficacy and safety study to evaluate AG10 800 mg compared to placebo in subjects with symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Learn more about these and see all amyloidosis clinical trials at UT Southwestern.

Lab research: Saelices Lab

Lorena Saelices, Ph.D., is a structural biologist and a biochemist with special interest in amyloid diseases. The main focus of the Saelices Lab is to uncover the mechanism of aggregation of transthyretin by determining the molecular structures of amyloid fibrils extracted from ATTR patients. Her team utilizes this structural information to design small peptide-based molecules to inhibit fibril polymerization as well as novel diagnostic tools. The Saelices Lab has other related research lines such as the study of the mechanism of neuroprotection of transthyretin on amyloid-beta aggregation in Alzheimer’s disease. Her discoveries enabled her to design effective peptide inhibitors of amyloid-beta toxicity and aggregation. Dr. Saelices aims to contribute to the understanding of the molecular mechanisms that underlie amyloid diseases to develop effective clinical tools.