Funding Provided the Impetus
Dr. Wilson focused initially on mountain biking and women racers because neither is well-funded, “and I knew a few women cyclists who were pretty good,” he says. To get the attention of the cycling community, and therefore sponsors, he recruited elite competitors at the national and international levels, including Bicycling Magazine’s “Fit Chick” columnist Selene Yeager.
Yeager and teammate Cheryl Sornson have been accepted to compete next spring in the most severe and competitive mountain bike race in the world, South Africa’s Cape Epic. Team members won some national races last year, and Dr. Wilson predicts that several of his racers will win national titles this season, also.
“We had to be realistic about who to recruit and what we could afford,” Dr. Wilson says. A professional road bike team is a sophisticated operation and could cost millions of dollars. Team CF doesn’t have that. It does have a group of sponsors, though, that includes pharmaceutical company Eurand, medical supply company Hill-Rom, nutritional firm Infinit, mountain biking pioneer Gary Fisher, mountain biking coach Chris Eatough, bike manufacturer Trek, components manufacturers SRAM and Bontrager, and clothing company Verge.
“We’re aligned with three clinical programs—the Children’s Hospital of Philadelphia, the University of Massachusetts Medical Center, and Johns Hopkins Medical Center,” he adds, noting that his team has partnered with the Cystic Fibrosis Foundation, which is hosting “Eurand CF Cycle for Life” biking events in 18 American cities this year.
As Holloway says, “I think Team CF is raising awareness, but it is only touching the tip of the iceberg. Since it is in its first year, people on the race circuit are still getting to know the team.”
Recognition of the team and of cystic fibrosis will improve, he predicts, as team members participate in more races. The CF Foundation’s Cycle for Life events help, but they are aimed at fundraising. For example, the foundation’s first cycling event attracted 87 riders and raised $88,000—76% more than the goal.
Team CF, in contrast, focuses upon fitness. As Dr. Wilson says, “The younger you can start them off, the better they will be, so we’re focusing on getting CF kids and young adults active.”
In the 1980s and ’90s Dr. Wilson was a technical ice climber who biked during the summer to keep in shape. (He since has switched to endurance mountain biking, competing on the national racing circuit.)
In 1989, he also was a Howard Hughes Medical Institute principal investigator at the University of Michigan. “I was the gene-therapy guy, and shared a floor with Francis Collins, who discovered the cystic fibrosis gene,” he says. So, when Dr. Collins’ “eureka” moment came, Dr. Wilson was close by.
That collegial relationship and a quirk of fate catapulted Dr. Wilson into the search for a cure for cystic fibrosis. As he recounts, when a speaker at the Cystic Fibrosis Foundation’s annual meeting cancelled, Dr. Collins asked him to fill in. The plan, he says, was to give a conceptual talk about gene therapy.
By July, however, Dr. Collins told him, “We’re close to finding the gene.” By September, the discovery was announced in Science. “The whole concept of the talk changed from conceptual to practical.
“It was an immensely exciting time,” Dr. Wilson recalls. When he walked into the lecture hall in October, “The energy in the room was palpable. People were so excited about the cloning of the gene. I was hooked. I devoted my career to discovering a cure for CF.”
In September 1990, he demonstrated that a gene could be transfected into a viral vector to cure cystic fibrosis in a Petri dish, he points out.
About the same time, William French Anderson, M.D., began the first human trial of gene therapy, in an attempt to cure severe combined immunodeficiency in a four-year-old girl. Breakthroughs seemed imminent, and the cystic fibrosis community watched the research with great anticipation. Developing an effective therapy, however, would take a long and complicated path.
“Like many others in the 1990s, we were focused on clinical applications for gene therapy using existing vector technologies,” Dr. Wilson explains. “That technology, however, was not up to the task, so for the past seven years, we have refocused on identifying new technologies.”
His group discovered a new family of adeno-associated viruses (AAVs) in human and nonhuman primates that undergo substantial recombination in vivo, and is developing designer vectors based upon them.
He says approximately 1,500 preparations of the vectors are distributed each year, and his lab makes “six to ten international shipments per week.” Many of these vectors, he says, offer an improved option for delivering genes to the lung, which has been a long-standing challenge for cystic fibrosis gene therapy. He also has used lentiviral vectors “to achieve stable and long-term gene transfer in nondividing cells,” he adds.
The field is seeing other improvements, too. “John Engelhardt, Ph.D., director of the Center for Gene Therapy at the University of Iowa, has developed a ferret model for cystic fibrosis,” Dr. Wilson says. That model will be used to evaluate some of Dr. Wilson’s new vectors for gene therapy as well as “to understand how stem cells in the adult airway respond to injury resulting from dysfunction of CFTR.”
As researchers learn more about the genomic basis of CF, the disease appears increasingly complex, with links emerging between the severity of CF and the development of type 2 diabetes. As other CFTR mutations and modifier genes are examined, additional influences may be uncovered. As yet, exactly how the CFTR protein triggers the disease remains unknown.
“It’s ironic. I have spent 20 years trying to develop an elegant, broad approach (to curing cystic fibrosis). Now the one thing I can do to help individuals today is to encourage exercise!” Dr. Wilson says.