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.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response:  Better understanding of long noncoding RNAs has the potential to open up entirely new gateways for us to tackle many diseases including heart disease.  Although the effects of long noncoding RNA can be compensated which makes it difficult to exploit therapeutically, if examined in the right context they may hold promising potential.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Whether treatment targeting LeXis or other components of that pathway in humans would have any effect on cholesterol levels or heart disease development  remains unknown and will be a focus of future studies along with validation  of our initial observations in other preclinical models.

For more information please see

http://newsroom.ucla.edu/releases/gene-therapy-using-junk-dna-could-lower-risk-for-heart-disease

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Citation: Long Noncoding RNA Facilitated Gene Therapy Reduces Atherosclerosis in a Murine Model of Familial Hypercholesterolemia

Peter Tontonoz, Xiaohui Wu, Marius Jones, Zhengyi Zhang, David Salisbury, Tamer Sallamhttps://doi.org/10.1161/CIRCULATIONAHA.117.029002
Circulation. 2017;136:776-778
Originally published August 21, 2017

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

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