Conquering hATTR Amyloidosis: Two Families Move Toward Hope

A disease that passes through generationally, the genetic disorder presents a constant family battle. But new treatments are on the way.

Hereditary ATTR (hATTR) amyloidosis is an inherited disease resulting from the deposition of abnormal proteins throughout the body. hATTR amyloidosis occurs from a mutation in the transthyretin (TTR) gene, which causes TTR proteins to misfold and deposit in multiple organs of the body where they shouldn’t be. The gene mutation is inherited in an autosomal dominant pattern, which means that a person may develop the disease if even one of their parents has the mutation (a 50% chance of inheritance).

The National Institutes of Health (NIH) classifies amyloidosis as a rare disease, meaning it affects less than 200,000 individuals in the US. The number of people living with hATTR amyloidosis is even more uncommon. Learn more in our hATTR amyloidosis overview.

Charles Horwath, 68, knew he was positive for hATTR amyloidosis when he was caring for his mother on her deathbed. She was suffering from the end stages of the disease and passed away soon after. At the time, he had not yet developed symptoms of his own.

“She was very sick at the time. She couldn’t leave her bed for months and required support for everything, from bathing to feeding to all of her day-to-day needs. She struggled with severe autonomic symptoms and was constantly in pain,” Charles told PPM. To date, 29 of Charles’ family members have been tested for hATTR amyloidosis, of which 19 have been positive.

Dawn Myers, 47, shared a similar experience. She got diagnosed with the condition while caring for her dying mother. She was genotyped for the disease during this time, and wanted to “plan her care accordingly,” she explained to PPM. Dawn is a fifth-generation patient; in her family, 19 out of 43 family members in the past six generations have suffered from hATTR amyloidosis.

Dawn described the generational nature of the disease. “I am a patient. I was a caregiver for my mother, my mother was a caregiver, and so on.” This experience is not uncommon for patients with hATTR amyloidosis.

Image: iStock (Olha Rohulya)hATTR Amyloidosis is a rare disease that can pass through family generations.

How Their Journeys Began

It wasn’t until 13 years after Dawn was genotyped (confirmed through a tissue diagnosis) for hATTR amyloidosis that her symptoms began. She described autonomic dysfunction (problems with the autonomic nervous system including heart rate, body temperature, breathing rate, digestion, and sensation), the inability to exercise due to neuropathic pain, and fatigue. Active for most of her life, these symptoms were difficult to bear. She was 44 years old at the time.

“[Their] were clear signals,” Dawn said. “Within six months, it felt like I couldn’t sleep through the night from neuromuscular pain. I would wake up to swollen hands [from a] lack of circulation. I was down to one pair of shoes because every [other] pair would hurt my feet.”

Charles started noticing symptoms of hATTR amyloidosis at the age of 60. He struggled with gastrointestinal issues such as diarrhea, nausea, and vomiting at first, all of which were hard to manage. Over time, the symptoms unfortunately got worse.

“Jump ahead three years, [and] all those symptoms at least tripled in severity. Add to that the neuropathy in my legs, feet, and toes,” he explained. “We are not a family that likes medicine, but I was forced to take morphine. It got so bad.”

“The disease also impacted my heart,” Charles explained. “It slows [your heartrate] down and gradually takes the function away, [which] gets worse and worse [and] brings on a whole new set of problems. I’d take a few steps, and I would get dizzy and faint. It got to the point where it was not safe to drive a car.”

In line with Dawn and Charles’s experience, symptoms of hATTR amyloidosis usually emerge during adulthood and worsen over time. The symptoms vary from patient to patient, depending on which organs and tissues are affected and how rapidly they progress. Commonly, the nervous, cardiovascular, and digestive systems are affected.

Image: iStockThe FDA has approved the two drugs that helped Dawn and Charles - patisiran (Brand name: ONPATTRO; Alnylam Pharmaceuticals) and inotersen (Brand name: Tegsedi; Ionis/Akcea Therapeutics) - for the treatment of hATTR amyloidosis with peripheral neuropathy, that is, weakness, numbness, and pain from nerve damage.

A Search for Solutions

In addition to blood tests for genotyping and tissue biopsies, Dawn underwent several other tests to assess the function of her various organ systems. “It is so overwhelming when you are first diagnosed. It feels like everything is crashing down on you,” she said.

Charles also described a very thorough evaluation. “They shock youusing electromyography to test and document the level and progression of your neuropathy, [they perform] eye tests, andthey also cut a one and a half-inch long piece of skin out of me,” he described. “They got biopsies from the mouth down – esophagus, stomach, intestines, colon. It was pretty invasive.”

Both Charles and Dawn’s diagnostic journey is typically the standard expected for this particular illness. A tissue biopsy of the abdominal fat pad and/or involved organ is used to confirm amyloidosis, and additional biopsies and tests are used to determine whether any other organs have been impacted. A genetic test performed on a blood or saliva sample is used to confirm a diagnosis of hATTR amyloidosis and identify the specific gene mutation.

After undergoing in-depth testing, both Charles and Dawn went through great lengths to get the treatment they needed.

“I was suffering,” Charles said. “I remembered what my mother went through.”

After discussing his options with his family, he made the decision to enter a drug trial. “It was so exciting. [The doctor] thought I could get better,” he recalled. “I was lucky to start treatment using Tegsedi (a hATTR medication that helps treat the polyneuropathy, or numbness/weakness, that occurs with the disease) five years ago.”

Slowly but surely, Charles found success through this treatment. “For the first time in years, there is hope for my family. Slowly my symptoms improved, and I [can] enjoy spending time with my grandchildren and playing an active role in their life with my wife.”

Dawn, on the other hand, knew that she needed more than what her primary clinician could offer. She “felt that for at least 8 months, the treatment [I was originally prescribed] (diflunisal) slowed things down,” despite “[starting] to progress anyway.”

She told her general practitioner that she wanted a referral to specialists at Boston University Medical Center. One of three main centers of expertise and research in the United States for hATTR amyloidosis, BUMC stood out to her as having a deepened understanding of her strain of hATTR amyloidosis, and her family members had been seeing hATTR amyloidosis experts from that institution since 1986.

“It was a fight to get to Boston but once I got there, I was on track for the treatment and specialists I needed to see to confirm all of my symptoms that I have had for [the past] 8 months. During that time, one of the drug companies opened up their expanded access protocol. I was fortunate enough to be accepted and start treatment on ONPATTRO (patisiran) in August 2017,” Dawn said.

Those with hATTR amyloidosis typically benefit the most from an individualized treatment plan developed in collaboration by their primary care provider and an amyloidosis specialist. Other clinicians may be a part of this team, such as a neurologist or cardiologist. This depends on the clinical presentation and organ systems affected.

The treatments were impactful for Charles and Dawn, but both of them acknowledge the continued day-to-day impact of living with hATTR amyloidosis. “I may never be where I was prior to disease onset,” Dawn said. “I was a cyclist. I was a daily gym person. I don’t know if I will be back there again.”

The Future Holds Promise

Liver transplantation has long been a common treatment method for hATTR amyloidosis, as the liver is the main source of abnormal TTR production and the procedure is most effective in patients who are in the early stages of the disease. Several other medications are emerging as therapies that provide hope to patients.

In 2018, the US Food and Drug Administration (FDA) approved the two drugs that helped Dawn and Charles - patisiran (Brand name: ONPATTRO; Alnylam Pharmaceuticals) and inotersen (Brand name: Tegsedi; Ionis/Akcea Therapeutics) -- for the treatment of hATTR amyloidosis with peripheral neuropathy, that is, weakness, numbness, and pain from nerve damage.

FDA has also recently approved tafamidis meglumine (Brand name: Vyndaqel; Pfizer, Inc.) and tafamidis (Brand name: Vyndamax; Pfizer, Inc.) for cardiomyopathy, a disease of the heart muscle that makes it harder for the heart to pump blood to the body, caused by hATTR amyloidosis.

“It’s interesting how things change within the generations,” Dawn shares. “My mom passed away right before she was approved for a liver transplant. For my uncle, the transplant extended his life 5 years. With my generation, I don’t have to think about that. I know there will be other acceptable treatments, and I won’t have to be so ill and lose major functions. I will never have to go down that road.”

Both Charles and Dawn also attend hATTR support groups, available nationwide, through Amyloidosis Support Groups.

Updated on: 05/28/20
Continue Reading:
hATTR Amyloidosis Overview