Literature Review
Tafamidis Delays Progression of Rare Polyneuropathy
Tafamidis, an oral non-NSAID and highly specific stabilizer of the TTR protein, delays neurologic progression in early-stage transthyretin...
LOS ANGELES—Patisiran, an investigational RNA interference therapy that suppresses the production of transthyretin (TTR) protein, significantly improves polyneuropathy in patients with hereditary TTR-mediated (hATTR) amyloidosis, according to phase III trial results described at the 70th Annual Meeting of the American Academy of Neurology.
David Adams, MD, PhD
After 18 months of treatment with patisiran, patients’ scores on a measure of neuropathy impairment had improved from baseline, whereas scores progressively worsened among patients who received placebo.
“The results are amazing,” said principal investigator David Adams, MD, PhD, Head of the Department of Neurology at Centre Hospitalier Universitaire Bicêtre in Paris. “The hope is to stop the progression of the disease and eventually to reverse it.”
Patients Often Present With Polyneuropathy
Formerly known as familial amyloidotic polyneuropathy, hATTR amyloidosis is a rare, multisystemic, progressive, life-threatening disease caused by mutations in the TTR gene. The mutations may cause misfolded TTR protein to accumulate as amyloid fibrils in the nerves, heart, and gastrointestinal tract. There are more than 120 known TTR mutations, and people with the most common mutation, Val30Met, often present with polyneuropathy. Patients with hATTR amyloidosis also may present with cardiomyopathy or a mixed phenotype. The median age of disease onset is 39.
In addition, hATTR amyloidosis may cause CNS symptoms (eg, progressive dementia, headache, ataxia, and seizures), autonomic neuropathy (eg, orthostatic hypotension, urinary retention, and sexual dysfunction), and peripheral sensorimotor neuropathy (eg, neuropathic pain, altered sensitivity, muscle weakness, and impaired balance). Current treatment options include liver transplantation.