Because the tetramer dissociation and misfolding of the monomer precede amyloid fibril formation, development of a small molecule that binds to TTR and stabilizes the TTR tetramer is an efficient strategy for the treatment of amyloidosis.
Minimum criteria for diagnosis of symptomatic disease have been agreed, which it is hoped will ensure diagnosis of ATTRamyloidosis at the earliest possible stage in people with a known TTR mutation.
Given that the pathogenic mutations lead to more aggressive forms of TTRamyloidoses, the mildly acidic condition might be more suitable for mechanistic studies of TTR misfolding and aggregation.
This retrospective analysis includes all patients referred to a single UK center in the last 25 years for clinical and laboratory assessment of known or suspected amyloidosis who underwent TTR gene sequencing.
Cardiac involvement in TTR-related amyloidosis (ATTR) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction.
Although they may be useful to ameliorate autonomic dysfunction in hereditary TTRamyloidosis, the impact of disease-modifying treatments on neurogenic orthostatic hypotension is still uninvestigated.
It is aimed at implementing appropriate and ongoing assessment of patients being treated for ATTRvamyloidosis, such that the effectiveness of management can be usefully assessed throughout the course of disease and management can be tailored according to the patient's requirements.
All three variants showed aberrant banding patterns that were similar to those of other well-characterized TTR variants, including the common Val30Met variant that causes ATTRamyloidosis.
In the Cox multivariate model, high-sensitivity troponin T (hsTnT; hazard ratio (HR) 1.003; confidence interval (CI) 1.001-1.005; p = 0.009) and mean pulmonary artery pressure (HR 1.061; CI 1.024-1.100; p = 0.001) were found to significantly and independently predict outcomes for AL amyloidosis, whereas QRS duration (HR 1.021; CI 1.004-1.039; p = 0.013), hsTnT (HR 1.021; CI 1.006-1.036; p = 0.006) and N-terminal pro-brain natriuretic peptide (HR 1.0003; CI 1.0001-1.0004; p = 0.002) were the best predictors for ATTRamyloidosis.