Investigational RNAi Drug Patisiran Show Promise in Hereditary Amyloidosis

MedicalResearch.com Interview with:
Prof. David Adams Head of the French National Reference Centre for Familial Amyloidotic Polyneuropathy (NNERF)/APHP/INSERM Paris FranceProf. David Adams
Head of the French National Reference Centre for Familial Amyloidotic Polyneuropathy (NNERF)/APHP/INSERM
Paris France

MedicalResearch.com:  What is the background for this study?

Response: Hereditary transthyretin amyloidosis is an autosomal dominant, multisystemic, progressive, life-threatening disease caused by mutations in the gene encoding transthyretin (TTR ).

The liver is the primary source of circulating tetrameric TTR protein. In hereditary transthyretin amyloidosis, both mutant and wild-type transthyretin deposit as amyloid in peripheral nerves and the heart, kidney, resulting in polyneuropathy and cardiomyopathy. Neuropathic changes result in profound sensorimotor disturbances, with deterioration in activities of daily living and ambulation, hypotension, diarrhea, impotence, and bladder disturbances.

Until now,  only few patients have access to anti-amyloid therapy : Liver Transplantation or TTR stabilizers which are able only to slow progression of the disease at very early stage of the disease.

Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin and is specifically addressed to the liver by lipid nanoparticle (LNP) formulation.

This study carried out a multicenter, international, randomized, double-blind, placebo-controlled, phase 3 trial of patisiran in patients with hereditary transthyretin amyloidosis with polyneuropathy.

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New Blood Test May Screen For ATTR Cardiac Amyloidosis

MedicalResearch.com Interview with:

Frederick L. Ruberg, MD Director, Cardiovascular Medicine Fellowship Training Program Director, Pilot Grants Program, Boston University Clinical and Translational Science Institute Director, Advanced Cardiac Imaging Program Section of Cardiovascular Medicine, Department of Medicine Department of Radiology Boston Medical Center

Dr. Frederick Ruberg

Frederick L. Ruberg, MD
Director, Cardiovascular Medicine Fellowship Training Program
Director, Pilot Grants Program, Boston University Clinical and Translational Science Institute
Director, Advanced Cardiac Imaging Program
Section of Cardiovascular Medicine
Department of Medicine
Department of Radiology
Boston Medical Center 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ATTR cardiac amyloidosis is an under-recognized cause of congestive heart failure in older adults that results from the deposition of misfolded TTR protein in the heart. One cause of ATTR cardiac amyloidosis is a genetic abnormality, inherited from an affected patient’s parent, that causes the protein TTR to misfold. The most common genetically inherited cause of ATTR amyloidosis in the US is called Val122Ile (V122I), named for the specific mutation in the TTR gene, that is seen in approximately 3.5% of US African Americans. ATTR cardiac amyloidosis was once an untreatable disease, but now new drugs are in different stages of clinical trial testing. Thus, recognition is important to get patients on the right treatments.

One of the principal reasons why the disease is under-recognized is that doctors don’t have proven and available diagnostic tests that can be applied in the outpatient clinic. This study demonstrated that a new point-of-care diagnostic test, using measurement of a blood protein called retinol binding protein 4 (RBP4) and other standard of care test information, can accurately diagnose ATTR cardiac amyloidosis. We demonstrated the validity of this test in two separate cohorts of patients with proven ATTR cardiac amyloidosis due to the Val122Ile mutation and control patients with heart failure but without amyloidosis.

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