The University of Nebraska Medical Center and its hospital partner,
The Nebraska Medical Center, have been selected as one of 12 sites participating
in a study using gene therapy techniques to treat cystic fibrosis (CF),
a genetic disease affecting approximately 30,000 children and adults in
the United States.
With cystic fibrosis, a defective gene causes the body to produce abnormally
thick, sticky mucus that clogs the lungs and leads to chronic, life-threatening
lung infections. These thick secretions also obstruct the pancreas, preventing
digestive enzymes from reaching the intestines to help break down and absorb
food. The chronic lung infections are responsible for shortening the life
expectancy for CF patients to a median of approximately 33 years. In addition,
many CF patients eventually develop diabetes.
Cystic fibrosis is really a difficult disease to treat because so many
organs are affected, said John Colombo, M.D., professor and chief of the
pediatric pulmonology section in the UNMC pediatrics department and a pediatric
pulmonologist for The Nebraska Medical Center. Its a great honor for
us to participate in this study. Were excited to be able to help in the
development of a potentially major new treatment for our CF patients. It
is exciting because it is one of the first therapies actually targeted
to treat the underlying defect.
CF is caused by a defect in a single gene. The CF gene tells cells how
to make a molecule called the CFTR protein, which is needed to keep the
proper water balance in the bronchial tubes and in linings of other internal
organs so they remain wet and clean. With CF patients, the CFTR gene has
the wrong instructions and cells cant make a CFTR protein that works properly.
Without this protein, the lung airways can become blocked with mucous secretions,
which can lead to severe, recurring respiratory infections.
Gene therapy, also called gene transfer, is an experimental procedure
that is being developed to treat a variety of diseases, including CF, by
putting normal copies of genes into cells that need them. Because genes
are located inside cells, transferring new genes from the outside of a
cell to the inside of a cell requires help.
In this study, a very small and simple virus, called AAV, has been
engineered in the laboratory to contain a normal copy of the CFTR gene.
AAV is not known to make people sick.
The AAV genes are taken out of the virus and a normal copy of the CFTR
gene is put in their place. This new gene combination is then put back
inside the virus. The combination of AAV and the CFTR gene that is being
tested in the current study is called tgAAVCF.
Once the virus has infected the cells lining the bronchi (the branching
airways within the lungs), the cells own machinery makes good CFTR from
the good copies of the gene supplied by the virus and will continue to
do so for the life of the cell.
Over the next several months, UNMC and The Nebraska Medical Center hopes
to enroll about 10 patients into the study, Dr. Colombo said. The study
provides for a total enrollment of 100 patients nationally. Two patients
have already been enrolled at the medical center and have started receiving
treatments.
Participants in the study will visit the CF center at the medical center
eight times. During two of these visits, participants will receive either
tgAAVCF or a placebo. Participants will not know during the treatment
if they are receiving the active drug or the placebo.
A nebulizer will be used to turn the drug or the placebo into an aerosol,
which participants will breathe in through their mouths. By breathing in
through their mouths, the drug or placebo will enter the airways in the
lungs. Once the drug enters the airway, it enters cells.
We are hoping that the normal copy of the CFTR gene carried by the
drug will provide the cell with the right instructions to make properly
functioning CFTR protein and thus result in more normal mucous secretions,
Dr. Colombo said.
Two patients enrolled in The Nebraska Medical Center/UNMC study are
Kate Howard, 16, of Sioux City, Iowa, and Chad Humston, 17, of Giltner,
Neb. Both participated in a news conference held at the Medical Center.
Cystic fibrosis is a disease that reminds you that its there every
day, said Lonnel Howard, Kates mother. Kate has never had one day of
normal living. We are so excited to have Kate participating in this study.
It represents hope for the future for all CF patients.
In an earlier Phase II study of the drug, Dr. Colombo said it
was determined that the drug appeared safe and didnt cause any serious
side effects. In addition, patients realized a statistically significant
improvement in lung function at 30 days after treatment in that study.
The phase II study has now been published in the February issue of Chest,
a leading scientific journal. It served as the basis for the current study,
a Phase IIb study, which is being conducted by Targeted Genetics Corporation
of Seattle, the company that manufactures the CF drug, and the Cystic Fibrosis
Foundation.
Gene therapy is one of the most exciting areas of scientific
research, Dr. Colombo said. It is a potential mode of therapy for any
disease with a genetic basis, so that can encompass lots of diseases, including
several forms of cancer. The use of gene therapy in CF is probably the
biggest breakthrough weve seen since the CF gene was discovered in 1989.
Currently, UNMC and The Nebraska Medical Center are participating
in two other gene therapy studies, said Ernie Prentice, Ph.D., associate
dean for academic affairs. These studies deal with breast cancer and prostate
cancer.
We have seen a marked increase in the number of gene therapy protocols
at UNMC in the last year, Dr. Prentice said, and we anticipate that we
will continue to see an increase in gene therapy studies in the future.
The CF gene therapy study is being administered nationally by
Childrens Hospital and Regional Medical Center in Seattle. For more information
on the study, call (402) 559-9256.