ATTR Flashcards
ATTR (Transthyretin Amyloidosis)
ATTR genetic mutations refer to a group of inherited genetic mutations that affect the production of transthyretin (TTR) protein.
TTR protein is produced mainly in the liver and plays a critical role in transporting thyroid hormone and vitamin A in the blood.
ATTR pathophysiology
Due to genetic mutations in the TTR gene, TTR protein becomes unstable, misfolded, and forms amyloid deposits in various organs.
Aggregate protein that forms are called fibrils
The TTRs can accumulate in the nerves, heart, and digestive system, leading to a range of symptoms and health problems.
Two most common types:
Polyneuropathy: peripheral neuropathy (damage to nerves outside the brain and spinal cord),
Cardiomyopathy (disease of the heart muscle), and gastrointestinal dysfunction
Two types of genetic roots
- Hereditary ATTR: caused by genetic mutation inherited in a autosomal dominate matter (hATTR-PN, hATTR-CM)
- Wild-type TTR: not caused by genetic mutations but the protein becomes unstable with age and prone to misfold (commonly affects the heart); much bigger patient population with hATTR
Gene edits needed?
TTR gene knock-down
Current treatment landscape
See pic
Current treatment paradigm
See pic
Comparison of the key pipeline products
See pic
Comparison of the key pipeline products (cont’d)
See pic
Upcoming catalysts
See pic
Main issue for Intellia in ATTR
See pic
PN endpoint
MNIS+7 from baseline
mNIS+7 stands for modified Neuropathy Impairment Score + 7, which is a clinical assessment tool used to evaluate the severity of ATTR-PN
mNIS+7 is a modification of the original Neuropathy Impairment Score (NIS), which was developed to assess peripheral neuropathy in patients with various types of neuropathies.
mNIS+7 includes seven additional assessments of autonomic neuropathy, which is the dysfunction of the nerves that control involuntary body functions, such as heart rate, blood pressure, and digestion.
The total score of mNIS+7 ranges from 0 to 304, with higher scores indicating more severe neuropathy.
CM endpoint
6MWT
6MWT stands for the 6-minute walk test, which is a simple and reliable test used to evaluate a person’s exercise tolerance and functional capacity. The test measures the distance a person can walk on a flat, hard surface in 6 minutes, with the goal of walking as far as possible in that time.
The 6MWT is commonly used in clinical settings to assess the functional status of patients with a range of conditions, including heart and lung diseases, peripheral arterial disease, and neuromuscular disorders.
All CV event mortality
Comparison of LNP vs AAV delivery
See pic
