Tafamidis for the treatment of transthyretin-associated familial amyloid polyneuropathy

Abstract

Introduction: Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a progressive neurodegenerative disease. Inherited in an autosomal dominant pattern TTR-FAP is characterized by sensomotor polyneuropathy and autonomic dysfunction with a fatal course. Liver transplantation is accepted as disease modifying treatment. Beyond this, no causal therapy had been on hand. Very recently, tafamidis was introduced as only pharmacotherapy available.

Areas covered: The report gives an overview of the complex clinical picture of TTR-FAP, describes molecular mechanisms of the disease as well as current standard of care and treatment options.

Expert opinion: The introduction of tafamidis in the treatment of TTR-FAP offers the first causal pharmaceutical approach. The drug is potent in limiting disease progression of amyloidosis. However, progression cannot be prevented, but occurs at a clinically relevant slower rate. The patients studied since 2007 did not reveal any relevant side effects. The European Medicines Agency has approved tafamidis in adult patients with Stage 1 symptomatic polyneuropathy. Based on our current knowledge, patients may benefit from tafamidis the more the earlier in the disease course it is administered. Among different approaches tested in the development of new drugs, tafamidis may serve as an ideal drug in future for combination therapy, for example, with RNAi therapeutics, antisense oligonucleotides and proteases involved in degrading amyloid fibrils in the tissue.

Keywords::

• amyloidosis
• familial amyloid polyneuropathy
• polyneuropathy
• tafamidis
• transthyretin

Declaration of interest

The author declares no conflict of interest and has received no payment in the preparation of this manuscript.

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