Hereditary systemic amyloidosis amyloidogenic transthyretin can be selectively suppressed

06-29-2006

A study from the United States has documented the targeted suppression of an amyloidogenic transthyretin (TTR) with antisense oligonucleotides.

"TTR amyloidosis, the most common form of hereditary systemic amyloidosis, is characterized clinically by adult-onset axonal neuropathy and restrictive cardiomyopathy. More than 85 mutations in transthyretin have been found to cause this hereditary disease," wrote M.D. Benson and colleagues, Indiana University.

They continued, "Since essentially all circulating TTR is of hepatic origin, orthotopic liver transplantation has been used as the only specific form of therapy. Unfortunately, in many patients amyloid deposition continues after orthotopic liver transplantation, indicating that mutant TTR is no longer required for progression of the disease after tissue deposits have been initiated."

"As a first step toward medical treatment of this disease, we have employed antisense oligonucleotides (ASOs) to inhibit hepatic expression of TTR. A transgenic mouse model carrying the human TTR Ile84Ser mutation was created and shown to express high levels of human mutant transthyretin. TTR ASOs suppressed hepatic TTR mRNA levels and serum TTR levels by as much as 80%," wrote the researchers.

The authors concluded, "Suppression of hepatic synthesis of transthyretin may offer a medical treatment for transthyretin systemic amyloidosis."

Benson and colleagues published their study in Muscle & Nerve (Targeted suppression of an amyloidogenic transthyretin with antisense oligonucleotides. Muscle Nerve, 2006;33(5):609-618).

For more information, contact M.D. Benson, Indiana University, School of Medicine, Department of Pathology & Laboratory Medicine, 634 Barnhill Dr., MS 128, Indianapolis, IN 46202, USA.

Publisher contact information for the journal Muscle & Nerve is: John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Keywords: Indianapolis, Indiana, United States, Amyloidosis, Antisense Oligonucleotides, Targeted Suppression, Amyloidogenic Transthyretin.

This article was prepared by Gastroenterology Week editors from staff and other reports. Copyright 2006, Gastroenterology Week via NewsRx.com.