Extend Survival in Familial Amyloid Polyneuropathy

Background

Hereditary transthyretin amyloid polyneuropathy (TTR-PN), also known as familial amyloid polyneuropathy, is a rare fatal systemic disease that causes sensorimotor polyneuropathy, autonomic dysfunction, cardiac failure, and gastrointestinal tract disorders. Death typically ensues within 7-10 years of disease onset.

The development of several disease-modifying therapies (DMDs), such as tetrameric TTR stabilizers (tafamidis), TTR gene silencing therapies with small interfering RNA (patisiran) and antisense oligonucleotides (inotersen), has significantly improved the outcome of this devastating disease. Past clinical trials indicated that DMDs could halt the progression of symptoms associated with the disease. However, whether these DMDs improve long-term survival in patients with TTR-PN remains unclear.

Results

A total of 201 consecutive TTR-PN patients were enrolled. The study compared the duration of survival after disease onset with and without DMDs. Disease onset was determined by the earliest patient-reported symptoms. DMDs significantly improved survival in both early-onset (<50 years old) and late-onset (≥50 years old) patients. DMDs also significantly improved survival in patients with later-onset disease (≥60 years old).

Conclusion

Innovative therapeutic approaches in neuromuscular disorders have the potential to significantly improve disease outcomes. The availability of DMDs that significantly improve long-term survival in patients with TTR-PN was made possible by the introduction of breakthrough gene-modifying treatments into the clinic. There is hope for even more effective therapy based on CRISPR-Cas9 technology, a gene editing approach that is currently being investigated in clinical trials.