Hereditary transthyretin (hATTR) amyloidosis is an ultra-rare condition caused by inherited mutations in the transthyretin (TTR) gene
- causes the liver to produce abnormal TTR protein, which accumulates as deposits in body tissues (amyloidosis)
- deposits can disrupt the structure and damage the function of affected tissues.
Because hATTR amyloidosis can affect tissues throughout the body, people may have a range of symptoms affecting 1 or more systems
- can include the autonomic nervous system, peripheral nerves, heart, gastrointestinal system, eyes and central nervous system
- effects and complications of the condition can lead to death within 3 to 15 years of symptoms developing
- thought to be around 150 people with hATTR amyloidosis in the UK (1)
Neuropathy in hATTR amyloidosis can be classified according to walking ability (described by Coutinho et al. 1980):
- Stage 1: people do not need help with walking and have mostly mild sensory and motor neuropathy in the lower limbs
- Stage 2: people need help with walking, there is progression of neuropathy in the lower limbs and symptoms develop in the hands (weakness and muscle wasting)
- Stage 3: people are wheelchair bound or bedridden and have severe sensory and motor neuropathy of all limbs.
People may mainly have symptoms of polyneuropathy or cardiomyopathy, but most patients seen in the NHS will have symptoms of both over the course of the condition
- in the UK, the most common genetic mutations associated with both polyneuropathy and cardiac involvement are Val122Ile (39%), Thr60Ala (25%) and Val30Met (17%)
- Val30Met mutation is associated with higher survival rates
- Val122Ile is primarily associated with cardiomyopathy
Inotersen is a novel, first-in-class 2'-O-2-methoxyethyl phosphorothioate antisense oligonucleotide that inhibits production of transthyretin (TTR) in adults with hereditary transthyretin (hATTR) amyloidosis
- Inotersen has a marketing authorisation for 'the treatment of stage 1 or stage 2 polyneuropathy in adults with hATTR amyloidosis'.
- NICE have recommended, within its marketing authorisation, Inotersen as an option for treating stage 1 and stage 2 polyneuropathy in adults with hereditary transthyretin amyloidosis
Patisaran is a ribonucleic acid interference agent that suppresses transthyretin (TTR) production by the liver (including abnormal TTR)
- NICE have recommended Patisiran , within its marketing authorisation, as an option for treating hereditary transthyretin amyloidosis in adults with stage 1 and stage 2 polyneuropathy (2)
Reference: