Until now, treatments for hereditary amyloidosis have largely consisted of interventions geared towards general patient support and amelioration of pain. At the American Neurological Association’s 145th Annual Meeting, Sami Khella, MD, gave a talk on new and emerging therapies for amyloidosis. After Dr Khella’s presentation, Neurology Learning Network caught up with him about the key advances in this area.

Dr Khella serves as chief of the Department of Neurology at Penn Presbyterian Medical Center, and a professor of clinical neurology at the University of Pennsylvania Perelman School of Medicine in Philadelphia, Pennsylvania.

Neurology Learning Network: What have been some recent research advances in the pathogenesis, clinical care, and features of hereditary myloidosis?

Dr Khella: There have not been any recent breakthrough findings in terms of pathogenesis. In terms of treatment, the gene-silencing drugs have been an amazing breakthrough method of slowing this disease down by silencing the gene that produces transthyretin protein, which causes hereditary amyloidosis among patients with a mutation in this gene.

NLN: Could you discuss the effects of hereditary amyloidosis on peripheral neuropathy?

Dr Khella: Hereditary amyloidosis is a fatal disorder of the peripheral nerves. It kills patients either by causing a progressive and terminal neuropathy, depending on the genetic mutation, or it can kill patients by a progressive cardiomyopathy. Also, it causes a general debility with severe weight loss and anorexia. All of those processes will impair patient's quality of life to a significant extent.

NLN: Could you discuss the treatment landscape for this patient population, as well as any potential options on the horizon?

Dr Khella: There are 2 gene-silencing therapies that have been approved for use among adults with this disease by the US Food and Drug Administration: inotersin (Tegsedi) and patisiran (Onpattro). They are very well-tolerated, and they are associated with dramatic improvements in slowing down peripheral neuropathy compared with placebo. They also alleviate the weight loss that is associated with this disease. Currently, both of these drugs are being tested for cardiomyopathy associated with hereditary amyloidosis, but they are not yet approved for this indication in the United States.

For cardiomyopathy, the transthyretin stabilizer tafamidis (Vyndaquel) is approved for cardiomyopathy among patients with hereditary amyloidosis. It has been shown to reduce all-cause mortality and hospitalizations from heart failure.

The off-label use of the non-steroidal drug diflunisal (Dolobid) is also an option that is currently available to patients. Like tafamidis, diflunisal will stabilize the transthyretin protein.

NLN: What key takeaways do you hope to leave with neurologists and neurology providers?

Dr Khella: I advise neurologists to test patients with a progressive neuropathy for hereditary amyloidosis, because it is a disease they should not be missing. Neurologists should try to diagnose this disease as early as possible among patients with a progressive sensory or sensorimotor neuropathy, because treatment delays result in ground lost that is not recoverable, as the open-label extension trials in this field have shown.

—Christina Vogt

Reference:
Khella S. Recent advances in amyloidosis: a disease you can't afford to miss. New and emerging therapies for amyloidosis. Talk presented at: American Neurological Association 2020 Virtual Meeting; October 4-9, 2020. https://2020.myana.org/program/sessions/recent-advances-amyloidosis-disease-you-cant-afford-miss