CRISPR Cas9 gene editing is still looked upon as a new phenomenon in medicine. Yet it appears in the news almost every week. This week Neurology Today shines a light on CRISPR’s role in hereditary transthyretin (hATTR) amyloidosis.
Amyloidosis is a rare disease that begins when an accumulation of amyloid, an abnormal protein, causes interference with various organs in the body.
Forms of Amyloidosis
There are several forms of amyloidosis, but ATTR amyloidosis mostly affects the nerves and the heart.
Hereditary Transthyretin Amyloidosis (hATTR)
hATTR is a very rare type of amyloidosis. TTR is an acronym for a protein called transthyretin which is made in the liver. When TTR changes to an abnormal shape or misfolds, it gives rise to fibrous clumps. The clumps may enter various organs or peripheral nerves causing them to malfunction.
Peripheral nerves are primarily affected by ATTR amyloidosis polyneuropathy (ATTR-PN). Polyneuropathy is a deterioration of nerves that spreads to the center of the body.
Mutations in the TTR gene are passed from either a father or mother. The amyloid buildup occurs mostly in nerves that are responsible for pain, heat, and touch. Life expectancy after diagnosis is about seven to ten years.
The CRISPR/Cas9 technology involves cutting a DNA sequence at a genetic location and either inserting or deleting DNA sequences. This changes a DNA single base pair.
The Potential of NTLA-2001
NTLA-2001 using CRISPR/Cas9 technology has the potential to become the first treatment to cure ATTR amyloidosis. A short-term study involving a small number of ATTR-vPN patients was conducted to evaluate the safety and tolerability of NTLA-2001.
Another important ‘first’ is that NTLA-2001 is based on CRISPR therapy which allows it to edit genes either through a vein or inside the human body (systemically).
An article published in the August 5th 2021 issue of the NEJM cited the dramatic reduction of the disease-causing transthyretin protein. Although the study was of short duration and involved six patients, experts were encouraged. It is believed that the treatment may be of benefit in alleviating mild disease for patients in the early stages.
A One Time Therapy
Michael Polydefkis, a neurology professor at Johns Hopkins, described the finding as revolutionary. He emphasized the need for future research and acknowledged that the current research was in its early stages.
However, Dr. Polydefkis sees the potential of a single sustained treatment of NTLA-2001 that would be preferable rather than a treatment each week or at slightly longer intervals.
The European Commission has granted NTLA-2001 orphan drug designation, which is the intent to accelerate its regulatory review and development.