Nav: Home

Substituting the next-best protein

April 24, 2020

When an actor is unable to perform in the theatre, an understudy--ideally one with some practice in the role--can take her place on stage. A study from Dr. Bernard Jasmin's laboratory at the University of Ottawa and published today in Nature Communications shows that the same is true of proteins. Its results point the way toward novel therapies for Duchenne muscular dystrophy.

Children born with Duchenne muscular dystrophy (DMD) have a mutation in the X-chromosome gene that would normally code for dystrophin, a protein that provides structural integrity to skeletal muscles. The loss of this protein causes severe symptoms, including deteriorating muscle strength beginning around the age of four. The average life expectancy of a child with this condition currently stands at 26 years.

While there is no cure, a promising area of research has developed around the protein utrophin, which is ~ 80% identical to dystrophin and even takes its place early during muscle development. Utrophin is produced from a gene on Chromosome 6 and can be expected to be intact in a DMD patient.

"Utrophin-based therapy is actually applicable to all DMD patients, regardless of their dystrophin mutation" says Dr. Christine Péladeau, the lead post-doctoral fellow on this project. "And this is not something we see with most other therapeutic approaches."

This study looked at a specific "IRES-dependent translation" pathway, which induces a cell's ribosome to trigger utrophin's production. The team tested 262 FDA-approved drugs to see which ones could most effectively activate IRES-mediated translation to boost utrophin expression in muscle. Two drugs that are currently on the market stood out as the strongest contenders--the beta receptor blocker Betaxolol and the cholesterol-lowering drug Pravastatin. When administered in a mouse model of DMD, these drugs each promoted increases in muscle strength close to that of healthy mice.

A number of advantages support targeting utrophin as a DMD therapy above more difficult approaches including dystrophin gene replacement using viral vectors. The repurposing of FDA-approved drugs can also speed the clinical trial process. The doses required are expected to be quite low, improving the chances of low toxicity.

What's more, utrophin seems to be involved in the body's own efforts to fight the disease.

"There is a tendency for DMD muscles to try to naturally upregulate the levels of utrophin, knowing that it doesn't have dystrophin," says Dr. Bernard Jasmin, who leads the lab where the work was conducted. "Obviously it's not enough, but in the absence of this endogenous upregulation, DMD would be a lot worse."

Further stimulation of that natural response via the identified pathway works with the body to strengthen muscles, without the danger of an adverse immune response to the therapy. It also demonstrates the promise of using IRES-mediated translation for therapeutic purposes. It serves as a proof of principle to bolster the idea that this method could be used in other diseases like cancer and neurodegenerative diseases.
-end-


University of Ottawa

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Our Relationship With Water
We need water to live. But with rising seas and so many lacking clean water – water is in crisis and so are we. This hour, TED speakers explore ideas around restoring our relationship with water. Guests on the show include legal scholar Kelsey Leonard, artist LaToya Ruby Frazier, and community organizer Colette Pichon Battle.
Now Playing: Science for the People

#568 Poker Face Psychology
Anyone who's seen pop culture depictions of poker might think statistics and math is the only way to get ahead. But no, there's psychology too. Author Maria Konnikova took her Ph.D. in psychology to the poker table, and turned out to be good. So good, she went pro in poker, and learned all about her own biases on the way. We're talking about her new book "The Biggest Bluff: How I Learned to Pay Attention, Master Myself, and Win".
Now Playing: Radiolab

Uncounted
First things first: our very own Latif Nasser has an exciting new show on Netflix. He talks to Jad about the hidden forces of the world that connect us all. Then, with an eye on the upcoming election, we take a look back: at two pieces from More Perfect Season 3 about Constitutional amendments that determine who gets to vote. Former Radiolab producer Julia Longoria takes us to Washington, D.C. The capital is at the heart of our democracy, but it's not a state, and it wasn't until the 23rd Amendment that its people got the right to vote for president. But that still left DC without full representation in Congress; D.C. sends a "non-voting delegate" to the House. Julia profiles that delegate, Congresswoman Eleanor Holmes Norton, and her unique approach to fighting for power in a virtually powerless role. Second, Radiolab producer Sarah Qari looks at a current fight to lower the US voting age to 16 that harkens back to the fight for the 26th Amendment in the 1960s. Eighteen-year-olds at the time argued that if they were old enough to be drafted to fight in the War, they were old enough to have a voice in our democracy. But what about today, when even younger Americans are finding themselves at the center of national political debates? Does it mean we should lower the voting age even further? This episode was reported and produced by Julia Longoria and Sarah Qari. Check out Latif Nasser's new Netflix show Connected here. Support Radiolab today at Radiolab.org/donate.