Friedreich's ataxia: An effective gene therapy in an animal model

April 6, 2014
The illustrations show a measurement of the activity of a mitochondrial protein (in blue) essential for cellular energy production, which is impaired when frataxin is absent (no staining in the untreated heart). Using gene therapy expressing frataxin, the activity of this essential protein can be corrected across the heart's entire surface. Credit: Inserm / H. Puccio

The team led by Hélène Puccio, director of research for Inserm at the Institute of Genetics and Molecular and Cellular Biology in close collaboration with Patrick Aubourg's team has demonstrated, in the mice, the efficacy of gene therapy for treating the heart disease associated with Friedreich's ataxia, a rare hereditary neuro-degenerative disorder.

The transfer, via a , of a normal copy of the gene deficient in patients, allowed to fully and very rapidly cure the in mice. These findings are published in Nature Medicine on 6 April, 2014.

Friedreich's ataxia is a severe, rare hereditary disorder which combines progressive neuro-degeneration, impaired heart function and an increased risk of diabetes. The condition affects one in every 50,000 birth. There is currently no effective treatment for this disease. In most cases, Friedreich's ataxia starts in adolescence with impaired balance and coordination (ataxia) of voluntary arm and leg movements, confining the majority of patients to a wheelchair after 10-20 years' progression. However, complications affecting the heart are the major cause of death in 60% of patients, most often before the 35 years of age.

The disease is caused by a common mutation in the FXN gene which leads to a dramatic decrease in the production of the protein named 'frataxin'. The reduced frataxin level disturbs the activity of mitochondria. These organelles are essential to cells and play a fundamental role in energy production. The nerve tissue (cerebellum, spinal cord etc.) and heart tissue are particularly vulnerable to this shortage of energy, which can lead to fatal heart failure.

The teams led by Hélène Puccio, director of research at Inserm and Patrick Aubourg have developed a therapeutic approach based on the use of an adeno-associated virus (AAV), which is known to efficiently target and express a therapeutic gene in heart cells. The virus was modified to make it harmless but nevertheless capable of introducing a normal copy of the FXN gene in the heart cells, thus leading to the expression of frataxin.

Hélène Puccio's team tested the efficacy of this treatment in a mouse model that faithfully reproduces the heart symptoms of patients suffering from Friedreich's ataxia. The results show that a single intravenous injection of AAVrh10 expressing frataxin is not only capable of preventing the development of heart disease in animals before the appearance of symptoms, but also, more impressively, of fully and rapidly curing the hearts of animals at an advanced stage of heart disease. After three weeks of treatment, the heart become fully functional again; mitochondrial function and the appearance of heart tissue being very similar to those of healthy mice. "This is the first time that has prompted full, lasting remission of heart disease so quickly in an animal model." explains Hélène Puccio.

As the central nervous system is also a target of AAV vectors, Hélène Puccio and Patrick Aubourg's teams are investigating whether a similar approach using gene therapy could be as effective for the spinal cord and cerebellum as it is for the heart.

Based on these promising results, work has begun on the necessary developments to propose to patients suffering from Friedreich's and presenting a progressive cardiomyopathy a treatment by gene therapy. To this end, three of the paper's authors have set up AAVLife, a French company specialising in gene therapy for rare diseases, to translate to clinic these important laboratory findings. A patent application has been submitted by Inserm Transfert for this gene therapy approach.

Explore further: Team finds gene therapy a promising tool for cardiac regeneration

More information: Study paper: dx.doi.org/10.1038/nm.3510

Related Stories

Team finds gene therapy a promising tool for cardiac regeneration

February 20, 2014
After a heart attack, there is often permanent damage to a portion of the heart. This happens, in part, because cardiac muscle cells are terminally differentiated and cannot proliferate after blood flow is blocked off to ...

What is the cost of rare diseases such as Friedreich's Ataxia?

February 27, 2013
What is the cost of rare diseases such as Friedreich's Ataxia? By analyzing direct and indirect costs of care research in BioMed Central's open access journal Orphanet Journal of Rare Diseases calculated that conservatively ...

Compound improves cardiac function in mice with genetic heart defect

February 20, 2014
Congenital heart disease is the most common form of birth defect, affecting one out of every 125 babies, according to the National Institutes of Health. Researchers from the University of Missouri recently found success using ...

Recommended for you

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.