Experimental gene therapy treatment for Duchenne muscular dystrophy offers hope for youngster

February 7, 2013, UC Davis

Jacob Rutt is a bright 11-year-old who likes to draw detailed maps in his spare time. But the budding geographer has a hard time with physical skills most children take for granted—running and climbing trees are beyond him, and even walking can be difficult. He was diagnosed with a form of muscular dystrophy known as Duchenne when he was two years old.

The disease affects about 1 in 3,500 newborns—mostly boys—worldwide. It usually becomes apparent in early childhood, as weakened skeletal muscles cause delays in milestones such as sitting and walking. Children usually become wheelchair-dependent during their teens. As is increasingly affected, the disease becomes life threatening and many patients die from in their 20s.

Today, Jacob is one of 51 children participating in a nationwide clinical trial for a new type treatment that could offer help to those suffering from devastating . Clinical researchers at UC Davis Medical Center and a handful other research centers around the nation are testing a high-tech drug designed to fix the underlying causing the progressive muscular decline that is seen in children with Duchenne.

"This type of genetic therapy is the most exciting treatment approach I have witnessed in my career for Duchenne muscular dystrophy," said Craig McDonald, professor and chair of the Department of Physical Medicine Rehabilitation at UC Davis, as well as principal investigator of the national clinical trial that Jacob is participating in. "We are hopeful that it will delay many of the disease's manifestations and ultimately improve life expectancy for patients."

Duchenne muscular dystrophy is caused by in the gene for the dystrophin. The protein is a stabilizer that protects ; without enough functional dystrophin, muscles become damaged, causing them to weaken and deteriorate over time.

Functioning a bit like a bridge over a dangerous chasm, the experimental drug—known as drisapersen—is designed to effectively cover over the specific genetic mutation, allowing the problem area to be skipped and causing cells to produce a slightly shorter – but functional – dystrophin protein.

Because Duchenne muscular dystrophy is rare and the drug addresses only a small subset of the genetic variants responsible for the disease, recruiting qualified patients was not easy. Of the medical centers involved in the study, UC Davis, with its highly regarded neuromuscular disease and physical medicine and rehabilitation expertise, enrolled the largest group of patients in the nation. For more than a year, its eight young participants, including Jacob, have been to Sacramento from as far away as Colorado, Utah and Arizona. For each participant, the clinical trial involved weekly injections, which meant Jacob had to fly from Southern California to the UC Davis clinic every Friday for 24 weeks.

"I've never seen such a complicated study in terms of logistics," said Erica Goude, who serves as the research coordinator at the UC Davis site. "We're collaborating closely with departments of pediatrics, cardiology, radiology and several others, and their outstanding commitment to the project has made our tasks much easier and more efficient. This study is an amazing team effort that I see frequently reflected in the smiles of our patients and their families."

The study also entails extensive physical testing to monitor each participant's progress over time. To assess each child's physical abilities and progress, participants complete a six-minute walking test specifically designed and validated by a UC Davis team that included McDonald and Erik Henricson, a UC Davis muscular dystrophy researcher. The six-minute test is now used worldwide in all ambulatory for Duchenne. Investigators also measure muscle strength and the level of dystrophin in the participants' muscles—the latter results obtained through muscle biopsies at several times during study. Of particular interest to the research teams are the residual effects of the drug several weeks after the injection series is completed.

Although McDonald says it is too early to draw conclusions from the current clinical trial, he suggests there is reason to be optimistic based on animal studies and evidence from another clinical trial in Europe. In that trial, patients and study investigators knew which patients were actually taking the experimental drug, meaning it was an "open" study. The current U.S. study is more rigorous because doctors and families are "blinded" about which drug regimen each participant has—either one of two dosages of the drug or a placebo—until the end of the study.

According to McDonald, the antisense oligonucleotide-mediated genetic therapy approach is particularly exciting because of its potential applications to most other variants of Duchenne and other genetic diseases. Although the current experimental therapy specifically addresses mutations in only one particular region of the gene, the same therapeutic concept can be applied to many others.

"If successful, this approach can be developed into specific gene therapy that represents truly personalized medicine," said McDonald. "Covering a mutation to restore a normal genetic open reading frame for protein synthesis can be a powerful approach for a variety of genetic diseases."

Standardizing the drug as a therapy for Duchenne patients still requires approval by the U.S. Food and Drug Administration. Investigators say the therapy could be similar to insulin injections for diabetes. But rather than daily injections, the Duchenne treatment might only involve weekly shots, which youngsters could learn to administer on their own.

Now that the clinical trial is closed at UC Davis to new enrollees, McDonald and his study team are completing the protocol for each participant and analyzing the resulting data. They expect results sometime in late 2013 or 2014 once all the participants around the country have completed the trial.

In the meantime, even though no one knows whether Jacob received the drug or a placebo, his family is feeling good about being in a clinical trial. According to Jacob's dad, Timothy Rutt, the family even hopes to use some of its new frequent flyer miles for upcoming vacations.

"Jake really enjoyed being part of the study,'" said the elder Rutt, who, as the editor of an online news publication called altadenablog.com, has written about his son's participation. "We were proud that he showed a great deal of courage throughout the trial and understood its importance to kids like him."

Explore further: New breakthrough could help treat muscular dystrophy

Related Stories

New breakthrough could help treat muscular dystrophy

August 13, 2012
A researcher in the Faculty of Medicine & Dentistry at the University of Alberta improved Duchenne muscular dystrophy symptoms in non-human lab models, using a new drug cocktail. The drug combination targets the “hot ...

Clinical trial of molecular therapy for muscular dystrophy yields significant positive results

July 25, 2011
A molecular technique originally developed at the University of North Carolina at Chapel Hill has taken one step closer to becoming a treatment for the devastating genetic disease Duchenne muscular dystrophy.

Docs: Heart device might be breakthrough for muscular dystrophy

October 17, 2012
(HealthDay)—A man with Duchenne muscular dystrophy who received a device to help his heart's left ventricle pump blood throughout his body could represent a breakthrough in the treatment of the disease, according to his ...

In new study, common drug reverses common effect of Becker muscular dystrophy

November 28, 2012
Cedars-Sinai Heart Institute researchers have found in an initial clinical trial that a drug typically prescribed for erectile dysfunction or pulmonary hypertension restores blood flow to oxygen-starved muscles in patients ...

A quantum leap in gene therapy of Duchenne muscular dystrophy

January 15, 2013
Usually, results from a new study help scientists inch their way toward an answer whether they are battling a health problem or are on the verge of a technological breakthrough. Once in a while, those results give them a ...

Recommended for you

Team identifies new mechanism essential for eye lens development

May 17, 2018
If you want to take clear photographs, you don't use sandpaper to clear a smudge from your camera's lens. Similarly, if you want to see clearly, the lens of your eye has to be free of obstruction.

Researchers identify gene that helps prevent brain disease

May 16, 2018
Scientists know that faulty proteins can cause harmful deposits or "aggregates" in neurological disorders such as Alzheimer's and Parkinson's disease. Although the causes of these protein deposits remain a mystery, it is ...

Sugars in infant formulas pose risk to babies with inherited metabolic disorder

May 16, 2018
Babies with inherited intolerance of fructose face a risk of acute liver failure if they are fed certain widely available formulas containing fructose, pediatricians and geneticists are warning. Baby formula manufacturers ...

New tool predicts eye, hair and skin color from a DNA sample of an unidentified individual

May 14, 2018
An international team, led by scientists from the School of Science at IUPUI and Erasmus MC University Medical Center Rotterdam in the Netherlands, has developed a novel tool to accurately predict eye, hair and skin color ...

Gene disruption signals cerebral palsy and autism link

May 10, 2018
University of Adelaide researchers have uncovered a genetic signal common to both cerebral palsy and autism.

Solving pieces of the genetic puzzle

May 10, 2018
Every living thing on the planet contains DNA, the molecular sequence that encodes the genetic blueprint of an organism. Genome sequencing can reveal your likelihood of getting certain diseases like Alzheimer's, and it can ...

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.