Hereditary ATTR amyloidosis: linking pathophysiology to potential therapeutic approaches

The treatment landscape for hATTR amyloidosis includes gene-silencing therapy, orthotopic liver transplant, TTR tetramer stabilizers, and immunotherapy
Adapted from Ueda M, Ando Y. Transl Neurodegener. 2014. doi:10.1186/2047-9158-3-19 and Sekijima Y. J Neurol Neurosurg Psychiatry. 2015;86(9):1036-1043.
*This visual represents approved and investigational approaches.

Current Treatment Options

Orthotopic liver transplant removes approximately 95% of the production of TTR. It has improved survival rates but does not permanently halt disease progression and requires lifelong use of immunosuppressants.2,3

  • Transplant may be less effective for patients who present primarily with cardiomyopathy
  • The limited availability of organs, as well as the exclusion of older patients and patients with advanced disease or with comorbidities, warrants the development of other treatment options

TTR tetramer stabilizers bind to the TTR protein and prevent the dissociation into monomers, but do not inhibit the synthesis of disease-causing protein.2,3

There are multiple investigational therapies in development that target different points in the disease pathway.1-4

Investigational therapies that may address the underlying cause of hATTR amyloidosis:

RNAi therapeutics are double stranded small interfering RNAs (siRNA) that bind to TTR mRNA and prevent production of TTR protein via the RNA interference pathway.1-3

Antisense oligonucleotides (ASOs) are short chemically modified oligonucleotides that bind to TTR messenger RNA (mRNA) and prevent production of TTR protein via ASO-RNAse H mediated cleavage.1-3

Therapies that may help to reduce fibril accumulation:

Monoclonal antibodies may suppress ATTR amyloid deposition by binding to amyloid fibrils and targeting them for immune system destruction.1,2,4

Fibril disruptors bind to amyloid fibrils and disrupt their association.1,2

Learn more about current clinical trials investigating treatment of hereditary ATTR amyloidosis.


  1. Ueda M, Ando Y. Transl Neurodegener. 2014. doi:10.1186/2047-9158-3-19.
  2. Sekijima Y. J Neurol Neurosurg Psychiatry. 2015;86(9):1036-1043.
  3. Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.
  4. Richards DB, Cookson LM, Berges AC, et al. N Engl J Med. 2015;373(12):1106-1114.
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