Eleven-year-old Jacob Rutt is a budding geographer who spends his free time drawing detailed maps while other kids play outside, running and climbing trees. Jacob was diagnosed with Duchenne muscular dystrophy (DMD) at age two, and even walking is difficult for him. He is one of 51 children participating in a clinical trial that may help him combat the disease that affects one in every 3,500 children.
Researchers at the University of California’s UC Davis Medical Center and a few other research centers around the country are holding the clinical trial. The medication being tested is a high-tech mixture that is designed to fix the underlying genetic defect that causes 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 in which Jacob is participating. “We are hopeful that it will delay many of the disease’s manifestations and ultimately improve life expectancy for patients.”
Duchenne muscular dystrophy affects mostly boys. Early in childhood a diagnosis made when delays in walking and sitting occur. The disease progresses, leaving children unable to walk and using a wheelchair for mobility. As the muscles of the heart begin to waste, the disease becomes life-threatening, and many die in their twenties. The disease is caused by a genetic mutation in the gene for the muscle protein known as dystrophin. Dystrophin stabilizes and protects the muscle fibers–without properly functioning dystrophin, muscles weaken and deteriorate.
The drug, known as drisapersen, is designed to patch the genetic mutation, allowing cells to produce slightly shorter, but functional dystrophin proteins. The drug will only help a small subset of the genetic variants responsible for the disease. Eight of the 51 participants in the study are monitored at UC Davis, and they must travel to the center for weekly injections for 24 weeks, with some coming from as far as Colorado, Utah and Arizona.
“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.”
Jacob and the other children are tested extensively to monitor any changes in physical abilities. The researchers are also looking at muscle strength and the level of dystrophin in the participants’ muscles. The dystrophin levels are tested following several biopsies throughout the trial.
“If successful, this approach can be developed into specific gene therapy that represents truly personalized medicine,” said McDonald, a researcher on the project who helped develop the six-minute walking test that is now used worldwide. “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.”
Only time will tell if Jacob received the drug or a placebo. Meanwhile, Jacob’s dad, Timothy Rutt, has been able to write about the family’s experiences in his blog called altadenablog.com, adding that Jacob has enjoyed being part of the study, and that the family plans to cash in the frequent-flyer miles and take a vacation once the trial is complete.
Do these clinical trials give you hope?