UCLA researchers from the Department of Chemistry and Biochemistry have developed a novel process to inhibit amyloid aggregation of Transthyretin, which is associated with three debilitating disorders including senile systemic amyloidosis (SSA), Familial Amyloidotic Polyneuropathies (FAP), and Familial Amyloidotic Cardiomyopathies (FAC).
Transthyretin (TTR) is a transport protein that is present in blood and cerebrospinal fluid. TTR is normally present as a tetramer and facilitates the important transport of retinol binding protein as well as thyroxine. Pathological disassociation of the TTR tetramer into monomers results in the self-association of TTR monomers into amyloid aggregates. These amyloids can then deposit into many organ systems, including peripheral nerves, heart, eye, skin, kidneys, and the gastrointestinal tract, causing several diseases including senile systemic amyloidosis (SSA), Familial Amyloidotic Polyneuropathies (FAP), and Familial Amyloidotic Cardiomyopathies (FAC). There is currently no cure for TTR-related amyloidosis and it is hypothesized that there exists segments on TTR itself that drives protein self-association into amyloid aggregates.
UCLA researchers have developed a novel method to inhibit TTR monomers from forming amyloids. Two segments of TTR have been identified and validated to be drivers of amyloid formation. Correspondingly, two optimized peptide inhibitors have been developed which target these TTR segments. These two peptides have been shown to disrupt amyloid formation and show a synergistic effect in a dose-dependent manner. These peptides were verified to not affect TTR stability or binding with its normal targets such as thyroxine.
|European Patent Office||Published Application||3478708||05/08/2019||2016-694|
Additional Patent Pending
Transthyretin, TTR, amyloid, amyloidosis, protein folding, self-association, neuropathy, cardiomyopathy, senile systemic amyloidosis, familial amyloidosis, peptide inhibitor, thyroxine, retinol binding protein