Other: THAOS is a noninterventional patient registry
THAOS is a noninterventional patient registry

Transthyretin (TTR) a 127-amino acid, tetrameric protein, primarily synthesized in the liver, is a secreted protein present in the blood and cerebrospinal fluid and is a carrier of thyroxine and retinol-binding protein-retinol (vitamin A) complex. Transthyretin-associated amyloidoses (ATTR) are diseases caused by dissociation of the transthyretin tetramer into monomers, which misfold, ultimately forming amyloid deposits in various organs. This structural instability of the TTR tetramer can occur due to genetic mutations of the gene encoding the TTR protein, or can be associated with aging. There are over 80 known mutations of TTR, which result in variable phenotypic expressions of amyloidosis that commonly affect the peripheral nerves, heart, kidney or vitreous.

ATTR with polyneuropathy (ATTR-PN) occurs when amyloid predominantly affects the peripheral and autonomic nerves. V30M (substitution of methionine for valine at position 30) is the most common mutation associated with this disease. The age of onset can be in the third or fourth decade of life or later, depending on the mutation carried and the patient's ethnic background. The main feature of ATTR-PN is progressive sensorimotor and autonomic neuropathy. Sensory neuropathy typically starts in the lower extremities followed by motor neuropathy within a few years. Autonomic neuropathy quite often accompanies the sensory and motor deficits. The lifespan for patients is severely shortened, with death occurring within 9-11 years from the first symptoms. The only demonstrated disease-modifying therapy for ATTR-PN is orthotopic liver transplantation.

ATTR with cardiomyopathy (ATTR-CM) occurs when the heart is predominantly affected. In this disease, also known as familial amyloid cardiomyopathy (FAC), amyloid fibrils infiltrate the myocardium, leading to diastolic dysfunction progressing to restrictive cardiomyopathy. ATTR-CM is late-onset with symptoms typically occurring in patients over 60 years old. One common mutation, V122I (substitution of isoleucine for valine at position 122), occurs with high frequency (prevalence of 3.9%) in African-Americans. The natural history of ATTR-CM is not well defined. In the elderly, wild-type (normal) transthyretin may become structurally unstable resulting in deposition of amyloid fibrils primarily in heart tissue and leading to restrictive cardiomyopathy and heart failure. Combined heart and liver transplantation is a current treatment option, however limited organ availability and significant patient co-morbidity limit transplant as a treatment option.

Various compounds have been shown to stabilize the TTR tetramer in vitro and in vivo, thus preventing TTR dissociation into monomers and formation of amyloid fibrils. Whether these TTR stabilizing compounds can positively impact disease progression is being evaluated in clinical trials in patients with TTR-associated amyloidosis. FoldRx Pharmaceuticals, Inc. is developing an investigational drug, Fx-1006A, as a novel, specific stabilizer of transthyretin for the treatment of TTR-associated amyloidosis.

The objectives of this survey are:

• To describe the population of patients affected with TTR-associated amyloidoses (ATTR), including hereditary ATTR and wild-type ATTR
• To enhance the understanding of disease natural history, including the variability and progression of the hereditary and acquired forms of the disease
• To better understand the genotype - phenotype relationship in hereditary ATTR
• To compare the progression of disease and overall survival in patients with hereditary ATTR with and without liver transplant
• To foster an international community of medical experts who will develop recommendations on the clinical management of ATTR
• To better understand, manage and treat patients with ATTR through publication of the survey data
• To evaluate treatment modalities that may benefit patients with ATTR