Exon skipping prevents formation of toxic protein fragments in Huntington's disease

February 11, 2014, Mary Ann Liebert, Inc
© 2014, Mary Ann Liebert, Inc., publishers

An innovative therapeutic strategy for reducing the levels of toxic protein fragments associated with Huntington's disease uses a new approach called exon skipping to remove the disease-causing component of the essential protein, huntingtin. Proof of concept using antisense oligonucleotides to "skip over" the specific exon in a mouse model of Huntington's disease is reported in an article in Nucleic Acid Therapeutics.

Melvin Evers et al., Leiden University Medical Center, The Netherlands, describe the successful use of antisense oligonucleotides to target the mutated exon that causes Huntington's disease in the article "Preventing Formation of Toxic N-Terminal Huntingtin Fragments Through Antisense Oligonucleotide-Mediated Protein Modification."

"No field of therapeutic development is moving faster, with more imminent clinical translation than the nucleic acid based treatment of central nervous system conditions," says Executive Editor Graham C. Parker, PhD, The Carman and Ann Adams Department of Pediatrics, Wayne State University School of Medicine, Children's Hospital of Michigan, Detroit, MI. "The novel therapeutic strategy outlined in Evers et al. gives us a proof of concept of how a previously intractable condition can be treated by modifying rather than removing the toxic protein."

The special issue also includes the Review article "A Chemical View of Oligonucleotides for Exon Skipping and Related Drug Applications." by Peter Järver, Liz O'Donovan, and Michael Gait, Medical Research Council, Cambridge, U.K. The authors explore the complex chemistry and design of used for exon skipping and progress in developing new chemistries to improve their stability and binding.

Annemieke Aartsma-Rus, PhD, Leiden University Medical Center, Guest Editor of the issue, emphasizes the need for scientists, clinicians, patients, regulators, and drug manufacturers to work closely together to develop exon skipping therapeutics, which are currently in clinical trials for neuromuscular disorders such as Duchenne muscular dystrophy and spinal muscular atrophy. These complex drugs and the challenging diseases they are targeting require a collaborative effort, she states in her Editorial "Antisense-Mediated Exon Skipping: Networking to Meet Opportunities and to Overcome Challenges."

Nucleic Acid Therapeutics is under the editorial leadership of Co-Editors-in-Chief Bruce A. Sullenger, PhD, Duke Translational Research Institute, Duke University Medical Center, Durham, NC, and C.A. Stein, MD, PhD, City of Hope National Medical Center, Duarte, CA; and Executive Editor Graham C. Parker, PhD.

Explore further: New study shows a breadth of antisense drug activity across many different organs

More information: The article, part of a special focus issue on exon skipping, is available on the Nucleic Acid Therapeutics website.

Related Stories

New study shows a breadth of antisense drug activity across many different organs

December 11, 2013
Antisense therapeutics, a class of drugs comprised of short nucleic acid sequences, can target a dysfunctional gene and silence its activity. A new study has shown that antisense drugs delivered systemically show activity ...

Can toxicity of a DNA drug be predicted and minimized?

August 27, 2013
New classes of therapeutic antisense oligonucleotides can have toxic effects on the liver. A novel machine learning-based approach used to predict the hepatotoxic potential of an antisense drug based on its chemical sequence ...

Drug delivery strategy eliminates myotonia symptoms in mice with myotonic dystrophy

February 22, 2013
By targeting the specific mutation that causes the hereditary neuromuscular disease myotonic dystrophy, it is possible to neutralize the mutant RNA toxicity and minimize or even eliminate the disabling symptoms of the disease. ...

New design guidelines simplify development of targeted therapies for muscular dystrophy and other diseases

January 30, 2013
The dystrophin protein offers critical support to muscle fibers. Mutations affecting dystrophin's expression cause the muscle-wasting disease muscular dystrophy. In Duchenne muscular dystrophy (DMD), these mutations take ...

Antisense oligonucleotides make sense in myotonic dystrophy

February 27, 2012
Antisense oligonucleotides – short segments of genetic material designed to target specific areas of a gene or chromosome – that activated an enzyme to "chew up" toxic RNA (ribonucleic acid) could point the way ...

Recommended for you

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

Scientists unleash power of genetic data to identify disease risk

January 16, 2018
Massive banks of genetic information are being harnessed to shed new light on modifiable health risks that underlie common diseases.

Blood-vessel-on-a-chip provides insight into new anti-inflammatory drug candidate

January 15, 2018
One of the most important and fraught processes in the human body is inflammation. Inflammatory responses to injury or disease are crucial for recruiting the immune system to help the body heal, but inflammation can also ...

Molecule produced by fat cells reduces obesity and diabetes in mice

January 15, 2018
UC San Francisco researchers have discovered a new biological pathway in fat cells that could explain why some people with obesity are at high risk for metabolic diseases such as type 2 diabetes. The new findings—demonstrated ...

Obese fat becomes inflamed and scarred, which may make weight loss harder

January 12, 2018
The fat of obese people becomes distressed, scarred and inflamed, which can make weight loss more difficult, research at the University of Exeter has found.

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.