Familial amyloid polyneuropathy is characterized by progressive neurologic deficits and disability which prove fatal if left untreated. Fewer than 10,000 people are estimated to be clinically affected worldwide, according to background information in the article. Diflunisal showed potential benefit in a phase 1 study.
John L. Berk, M.D., of the Boston University School of Medicine, and colleagues, pursuing the NIH mission to repurpose old drugs, randomized 130 patients from Sweden, Italy, Japan, England, and the United States to receive diflunisal (n=64) or placebo (n=66) twice daily for 2 years to determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy.
Patients randomized to diflunisal exhibited less progression of polyneuropathy than those assigned to placebo. The inhibitory effect of diflunisal on neuropathy progression was detectable at 1 and 2 years, and at 2 years, 29.7 percent of the diflunisal group compared to 9.4 percent of the placebo group exhibited neurological stability. Physical quality of life stabilized from the beginning of the study to 2 years in those assigned to diflunisal treatment while decreasing in the placebo group.
The authors write that their trial is pivotal for several reasons: it is the first randomized trial involving a broad cross-section of the spectrum of disease; it provides invaluable natural history data on the rate of neurological disease progression; and it establishes that diflunisal, a low-cost treatment, is well tolerated by familial amyloid polyneuropathy patients with a spectrum of neuropathy.
"Although longer-term follow-up studies are needed, these findings suggest benefit of this treatment for familial amyloid polyneuropathy."