The TRITON program of studies is evaluating the investigational medication, nucresiran, for the treatment of ATTR amyloidosis with cardiomyopathy and hereditary ATTR amyloidosis with polyneuropathy.
Nucresiran
Nucresiran is a potential RNAi therapeutic that is being evaluated as a silencer drug to reduce the hepatic synthesis of transthyretin (TTR) protein.
RNAi is a naturally occurring cellular mechanism for regulation of gene expression, mediated through the binding of small interfering RNA (siRNA) to its complementary messenger RNA (mRNA) sequence. This mechanism leads to mRNA cleavage and subsequent suppression of the synthesis and levels of the target protein.
Since the liver is responsible for the major rate of TTR degradation and the goal of nucresiran is to suppress hepatic production of it, nucresiran is expected to reduce the expression of circulating TTR protein to alleviate the symptoms of ATTR amyloidosis.
ATTR amyloidosis
Transthyretin-mediated amyloidosis (ATTR amyloidosis) is a serious, multisystemic, underdiagnosed disease resulting in progressive and debilitating morbidity and mortality. It is a systemic disorder characterized by the extracellular deposition of amyloid fibrils derived from misfolded TTR protein.
Results from causes that are either:
(hATTR) – pathogenic mutations in the TTR gene ( >140 known mutations)
(wATTR) – age‑related destabilization of TTR
Clinical manifestations of ATTR amyloidosis include
cardiomyopathy and polyneuropathy.
ATTR amyloidosis with cardiomyopathy is a result of cardiac infiltration by TTR amyloid fibrils and leads to:
- Chamber stiffness
- Progressive increase of ventricular wall thickness
- Impaired diastolic and systolic function
ATTR amyloidosis with cardiomyopathy is a result of cardiac infiltration by TTR amyloid fibrils and leads to:
- Chamber stiffness
- Progressive increase of ventricular wall thickness
- Impaired diastolic and systolic function