A Race Against Time for Duchenne Muscular Dystrophy

Photo Aug 03, 7 26 04 PM

Gabe Griffin’s dad, Scott, says one thing is certain about him: “He’s a fighter.” Gabe is in the sixth grade at Chelsea Middle School. Photo by Andrew Garza.

Written by Madoline Markham
Photography by Beau Gustafson 

Gabe Griffin believes he won’t have Duchenne muscular dystrophy when he gets older, but he is in a race against time.

When he was diagnosed at age 3, doctors told his parents Scott and Traci he would be wheelchair bound by age 10 to 12. He’s now 11 and ambulatory, but he has trouble walking up stairs and getting up as his muscles are deteriorating. His parents constantly face a series of decisions. As one example, can Gabe go to his older brother’s paintball birthday party, knowing that for those with Duchenne breaking a bone especially waist down will probably disable them from walking?

Duchenne, one of the nine types of muscular dystrophy, typically only affects boys (1 in 3,600) with muscle deterioration symptoms starting at a very young age. About 150 people in Alabama have it, and about 200 come to the Duchenne clinic at Children’s of Alabama.

If Gabe reaches the point where he becomes wheelchair-bound, he will likely have to have surgery where his Achilles heel is cut, have a steel rod put in his back to stop scoliosis, and later use a feeding tube and breathing tube. As the disease progresses, he would have to be turned every hour during the night to prevent bed sores, and he would not be able to go to the bathroom on his own. Usually people with Duchenne do not live beyond ages 17 to 25.

The cause of the disease was discovered in 1986, but 30 years later, there is still no treatment for the version Gabe has. The only thing on the market that helps keep him are steroids, which also stunt his growth and come with a host of other side effects.

For the past five years the Griffins and their nonprofit organization, Hope for Gabe, have been fighting to get a drug called Exondys 51 approved. It will help the majority of boys in the country with Duchenne, about 13 percent, but not Gabe. A drug that could treat Gabe’s four gene deletions—starting with No. 43—is still in the discovery phase as about No. 7 of 10 Duchenne treatments pharmaceutical companies are working on.

The earlier you get medication to a child, the better. Exondys 51 has been shown to slow and sometimes stop the progression of the disease, and a lot of patients who were in the clinical trial for it are still walking at age 13 to 15. Overall, it doesn’t reverse the disease, but it can stop it. But still, if you are not ambulatory, it can’t make you walk again. It enabled a 19 year old who couldn’t walk to drink a cup of water on his own again after 19 doses of the medicine.

“That’s why we are in a race against time,” Scott says. “I can’t control how long (Gabe) walks…but we are doing everything we can… My goal is to get 43 as fast as possible.”

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Dr. Matthew Alexander researches Duchenne muscular dystrophy in zebrafish at a new lab at UAB. Photo by Beau Gustafson.

Enter Dr. Matthew Alexander. As a post-doctoral fellow at Boston Children’s/Harvard Medical School, Alexander worked under Dr. Louis Kunkel, a researcher considered the “father of Duchenne” for discovering its cause, the absence of a protein called Dystrophin, in 1986. It was there that Alexander first studied Duchenne in zebrafish. “I was fascinated how quick we could get useful data from the fish, and how closely the DMD disease mimicked what was happening in the patients,” Alexander says.

Six years after beginning his work under Kunkel, Alexander opened his own lab in January at Children’s of Alabama/UAB to continue his research of developing new models of muscular dystrophies and novel drug compounds. The first time Scott emailed Alexander he sent a Duchenne paper on a gene called Jagged 1 that Scott had read recently. As it turns out, Alexander’s colleague from Harvard was the first name on the paper, and the second was his own. Scott’s reaction? “Wow, we have the real
deal here.”

The zebrafish work especially well for screening drug candidates because of their low cost, large number of offspring, and how they rapidly absorb drug compounds through skin and gills. “We can observe the zebrafish embryos and larvae under a microscope and watch as they form their muscles and observe at what stages the DMD muscle defects begin to appear,” Alexander says. “But the biggest advantage is that we can rapidly screen through thousands of drug candidates in a matter of weeks, where it would take years to do in mice. If we can show that a compound 2 vertebrate models of DMD, then the likelihood of being effective in DMD patients increases dramatically.”

Currently the lab is working on a class of compounds to block the inflammation process often associated with Duchenne. Because the compounds they found work well in zebrafish, they are now testing them in mice, and from there are hoping to get funding for pre-clinical studies so that they can be be used with other compounds being tested to delay muscle weakness that comes with Duchenne.

“We have someone who is not only brilliant but is brilliant about Duchenne,” Scott says of Alexander. “That thrills us beyond belief…We are hopeful that he’ll be able to streamline or speed up something to help Gabe and all patients with Duchenne.”

As for Alexander, he sees the Griffins as fantastic advocates of raising money for Duchenne research and faster approval of drugs for the condition. It’s his desire for families facing the disease to learn his research and the people behind it. “I want them to know that those of us working at the bench are motivated by their support, and it keeps us going during those times in the lab when experiments don’t work,” he says. “It is their efforts that really inspire us every day to work on helping find new ways to fight these debilitating neuromuscular diseases.”

The company behind Exondys 51, Sarepta Therapeutics, is now partnering with two other pharmaceutical companies that are developing complementary treatments for Duchenne, including one that would enable patients like Gabe to start making the utrophin his body has never made and hence start to repair the dead muscle. This could reverse some of the damage of the disease instead of just treating it. The partnerships make Scott think that the companies foresee a “cocktail” of drugs that could save those with Duchenne. Scott hopes that Alexander’s lab will get involved with one or two or three of those companies to push them along.

All in all, Gabe gets his optimism from his dad, who believes boys now living with Duchenne will be the first generation to survive it. But the time line is still uncertain. “You just hope and pray that we can keep (Gabe) as healthy as long as possible until we can get a drug that helps him,” Scott says. “And that’s why Dr. Alexander’s work is so important…It’s amazing to be in a position where you can actually truly save lives every day by your work…At the end of the day, I’m Gabe’s dad, and I want to save his life—end of story.”

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