Rethinking Rare Disease Gene Therapy Trials In The Era Of CRISPR-Cas9

By QPS

Transthyretin amyloidosis (ATTR amyloidosis) is a rare but fatal disease marked by clumping and accumulation of mutated, misfolded transthyretin proteins in peripheral nerves and cardiac tissue. Most patients experience neuropathy and/or cardiomyopathy, and average survival from disease onset is between two and 17 years. About 50,000 people worldwide have its autosomal dominant inherited form.

Current therapies, which have only become available in recent years, aim at reducing amyloid protein accumulation, either by binding to the TTR tetramer or disabling amyloid messenger RNA, also known as “RNA silencing.”  These options can reduce accumulation by up to 80 percent, but they require ongoing treatment to maintain those levels, often have severe side effects, and only slow disease progression — but there is new hope. A recent paper published in the New England Journal of Medicine and discussed in Nature details promising early phase data for a therapy that may not only offer a new option for patients, it may usher in a new era of medicine.