Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Proof of Concept: Gene therapy for mitochondrial diseases

25.09.2018

Mitochondrial disease is now thought to be the second most commonly diagnosed genetic disease worldwide, and, unfortunately, there are still no proven treatment strategies for those diagnosed. Scientists from the Max Planck Institute for Biology of Ageing in Cologne were involved in collaborations to apply gene-therapy approaches in mice to successfully treat an animal model of mitochondrial disease. This may pave the way for future therapeutic strategies for patients.

Every step we take, every laugh we make, every word we say requires energy. Mitochondria play a central role in our metabolism and energy production. Consequently, mitochondrial dysfunction causes a remarkably diverse group of metabolic diseases with a broad range of symptoms leading to severe disability.


A virus-infected cell in a cell culture surrounded by uninfected cells. Mitochondria are shown in green. The virus shown in orange-red (left cell) is located to the mitochondria. Scale bars: 10 μm

©Mitochondrial Biology Unit, University of Cambridge

“Since the 1980s it was known that mutations in the mitochondrial DNA can lead to disease” explains James Stewart, group leader at the Max Planck Institute for Biology of Ageing and continues “we have known of these patients for over 30 years and only now are we starting to develop treatments”.

A remarkable feature of mitochondria is that they contain their own DNA. Mutations in this mitochondrial DNA (mtDNA) can lead to mitochondrial diseases, but whether a person with a mutation develops disease or not is more complex.

Many copies of mtDNA are present in each of our cells and, normally, disease-causing mutations are present in only a fraction of them. However, if the fraction of mutated mtDNA molecules rises above a certain threshold, mitochondrial function is compromised resulting in mitochondrial disease. Therefore, reducing the levels of mutated mtDNA molecules is a potential treatment strategy.

However, this treatment strategy is not so straightforward as conventional gene-therapy approaches do not work in mtDNA. Scientists from the University of Cambridge, UK and the University of Miami, USA, developed an approach to specifically degrade mutated mtDNA molecules in cell culture.

Using a modified virus, they delivered a gene into the cell nucleus that encodes a protein that works as molecular scissors. These molecular scissors are then produced by the cell and targeted to mitochondria, where they specifically cut the mutated mtDNA.

But would the method also work in complex organisms composed of many tissues like mice or humans and actually treat mitochondrial disease? Stewart and his colleagues in Cologne could provide the answer. They had generated a mouse model of mitochondrial disease that contains a specific disease-causing mutation in mtDNA which leads to disorders in cardiac and muscular tissue.

They treated the animals with the virus that only infected the heart or the muscles. The virus delivered the molecular scissor to cut the mutated mtDNA in the targeted tissue. And in fact, the approach worked! The levels of mutated mtDNA were reduced and the disease symptoms were alleviated.

“This is the first gene therapy to actually remove the cause of a mitochondrial disease in a living animal” a delighted Stewart tells us. Of course, before the therapy can be applied to human patients more detailed work and safety assessments must be done.

Nevertheless, the scientists could prove that they found a way to remove the cause of these mitochondrial diseases. And since there is a link between mitochondrial dysfunction and other conditions like Alzheimer’s disease, Parkinson’s disease, diabetes, and perhaps some cancers, the approach will might even have a higher impact in fighting those disorders in the future.

Wissenschaftliche Ansprechpartner:

Dr. James Stewart
Max Planck Institute for Biology of Ageing
Phone: +49(0)221 379 70 706
E-Mail: JStewart@age.mpg.de

Originalpublikation:

Payam A. Gammage, Carlo Viscomi, Marie-Lune Simard, Ana S. H. Costa, Edoardo Gaude, Christopher A. Powell, Lindsey Van Haute, Beverly J. McCann, Pedro Rebelo-Guiomar, Raffaele Cerutti, Lei Zhang, Edward J. Rebar, Massimo Zeviani, Christian Frezza, James B. Stewart and Michal Minczuk: Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo. Nature Medicine, 2018 DOI: 10.1038/s41591-018-0165-9.

Dr. Annegret Burkert | Max-Planck-Institut für Biologie des Alterns
Further information:
http://www.age.mpg.de

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: memory-steel - a new material for the strengthening of buildings

A new building material developed at Empa is about to be launched on the market: "memory-steel" can not only be used to reinforce new, but also existing concrete structures. When the material is heated (one-time), prestressing occurs automatically. The Empa spin-off re-fer AG is now presenting the material with shape memory in a series of lectures.

So far, the steel reinforcements in concrete structures are mostly prestressed hydraulically. This re-quires ducts for guiding the tension cables, anchors for...

Im Focus: Goodbye, silicon? On the way to new electronic materials with metal-organic networks

Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz (Germany) together with scientists from Dresden, Leipzig, Sofia (Bulgaria) and Madrid (Spain) have now developed and characterized a novel, metal-organic material which displays electrical properties mimicking those of highly crystalline silicon. The material which can easily be fabricated at room temperature could serve as a replacement for expensive conventional inorganic materials used in optoelectronics.

Silicon, a so called semiconductor, is currently widely employed for the development of components such as solar cells, LEDs or computer chips. High purity...

Im Focus: Storage & Transport of highly volatile Gases made safer & cheaper by the use of “Kinetic Trapping"

Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles

Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...

Im Focus: Disrupting crystalline order to restore superfluidity

When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.

We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...

Im Focus: Micro energy harvesters for the Internet of Things

Fraunhofer IWS Dresden scientists print electronic layers with polymer ink

Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

Conference to pave the way for new therapies

17.10.2018 | Event News

Berlin5GWeek: Private industrial networks and temporary 5G connectivity islands

16.10.2018 | Event News

 
Latest News

Weighing planets and asteroids

23.10.2018 | Physics and Astronomy

Fiber-based quantum communication - Interference of photons using remote sources

23.10.2018 | Information Technology

'Mushrooms' and 'brushes' help cancer-fighting nanoparticles survive in the body

23.10.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>