Experimental gene therapy treatment for Duchenne muscular dystrophy offers hope for youth.
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 2 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 heart muscle is increasingly affected, the disease becomes life threatening and many patients die from heart failure 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 neuromuscular disease. 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 genetic defect 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 and 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 genetic mutations in the gene for the muscle protein dystrophin. The protein is a stabilizer that protects muscle fibers; 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.”