Scientists edge closer to treatment for myotonic dystrophy

April 29, 2020

In a paper published today in the journal Science Translational Medicine, scientists from the Schools of Life Sciences and Chemistry at the University, have discovered that by inhibiting a molecule in patients' cells called CDK12, they can potentially develop a therapy to alleviate some of the symptoms, and help treat this incurable condition.

Myotonic dystrophy is a long-term genetic disorder that affects muscle function. It is the most common form of muscular dystrophy in adults and affects about one in 8,000 people. There is currently no treatment available.

Symptoms include gradually worsening muscle loss and weakness. Muscles often contract and are very slow to relax. Other symptoms may include cataracts, intellectual disability and heart conduction problems.

Some patients have a very mild form and others have severe form, where they are congenitally affected from birth.

This is due to the molecular underpinning of the condition, which is caused by a dynamic mutation; a triplet repeat expansion, in which three base pairs of DNA are present in different copy numbers. In the general population people have 5-30 copies of this DNA sequence.

In patients with myotonic dystrophy- this particular segment of DNA becomes bigger than it is in the general population, often with hundreds of copies of the triplet repeat.

The faulty gene produces a faulty RNA which contains the expansion sequence, (RNA is a macromolecule essential for all known forms of life which transfers information from DNA in the nucleus to the cytoplasm of a cell where it makes proteins). The faulty RNA gets stuck in the nuclei of myotonic dystrophy patients' cells, resulting in disruption to many cellular processes.

In this new study, scientists have discovered that through the inhibition of the molecule CDK12 - the additional faulty RNA disappears, and so reduces the symptoms of the condition.

David Brook, Professor of Human Molecular Genetics in the School of Life Sciences, is the lead researcher on the study, He said: "Through our research we now understand a key molecular component in the pathway of the condition and that's a target for us to try to inhibit this particular CDK12 protein which will then have beneficial effects in terms of developing a treatment.

"Transcription is the process by which RNA is made from DNA and this can require CDK12. When the repeat sequence is transcribed, it makes the faulty expansion RNA - but we think that the myotonic dystrophy patients' cells struggle to make the faulty RNA and they increase their levels of CDK12 to keep ploughing through the expansion sequence and make more of this RNA because the cell doesn't know this is toxic.

"What we've found is that our inhibitors affect the function of CDK12 and so prevent the transcription of the faulty RNA which offers a possible route to a treatment of the condition.

"We are now at the stage where we know if we can inhibit CDK12 selectively - then it's going to be a potential therapy - and now we are trying to work out how to do that."
-end-


University of Nottingham

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.