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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RNA-Editing Tool Corrects Collagen Deficit in Severe Blistering Disorder

MedicalResearch.com Interview with:
http://www.proqr.com/team-and-boards/Daniel de Boer
Founding Chief Executive Officer
ProQR

MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by dystrophic epidermolysis bullosa?

Response: Dystrophic epidermolysis bullosa (DEB) is caused by a mutation in the COL7A1 gene which is responsible for the formation of a protein called type VII collagen (C7). This protein helps bind the inner and outer layers of the skin together. Mutations in one part of COL7A1 gene, exon 73, are the most common cause of DEB resulting in a non-functional C7 protein. ProQR’s QR-313 is designed to skip exon 73 of the COL7A1 gene, leading to a shortened C7 protein called C7Δ73. The current studies are intended to determine whether C7Δ73 functions the same as normal C7 protein. This mechanism can hopefully restore normal skin function for DEB patients.

DEB is a rare genetic skin disease characterized by easy blistering of the skin, poorly healing wounds and skin infections. DEB is present at birth and in severe cases leads to skin cancer, which can significantly reduce a patient’s lifespan. There are currently no treatments for DEB that target the underlying cause of the disease. The current standard of care consists of expensive time-consuming wound care, antibiotics to prevent infection and pain medications. As a result, this disease presents a huge burden to the patients themselves, as well as people who help with daily care.

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Familial Hypercholesterolemia: “Junk” RNA May Facilitate Gene Therapy

MedicalResearch.com Interview with:

Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 

Dr. Sallam

Tamer Sallam, MD PhD
Assistant Professor of Medicine
Co-Director UCLA Center for Lipid Management
Lauren B. Leichtman and Arthur E. Levine CDF Investigator
Assistant Director, STAR Program
Division of Cardiology, Department of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, California 90095-1679

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

Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease.

In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases.

Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments.

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