BREATHING
BREATHING INSTITUTE
AIR BALL
A NEW CYSTIC FIBROSIS DRUG LETS CALEB NOLAN LIVE
HIS BASKETBALL DREAMS
He was less tired
and got sick less
often. His fourth
grade school
attendance record
was perfect.
Meet Caleb
Caleb Nolan, 10, ducks past his 8-year-old sister Haley and
drives the court: a layup ricochets off the backboard and
misses the hoop. Caleb snaps up the falling ball and drives
the other way, tries again.
Caleb lives and breathes basketball.
His basketball card collection
numbers in the hundreds; he
can rattle off player statistics on
demand. His mom, Melissa Nolan,
looks on as he heads back down
the court.
“He’ll do this all day.”
Which isn’t so incredible in itself.
What’s incredible in Caleb’s case is
that he has cystic fibrosis (CF).
“There are over 1,900 known
genetic mutations and variants in
cystic fibrosis, and each is linked
with a particular abnormality in the
protein,” says Scott Sagel, M.D.,
Ph.D., Caleb’s primary CF physician
at Children’s Hospital Colorado.
“Caleb’s particular mutation, among
the 10 most common mutations
in the U.S., leads to a gating
abnormality where a protein is
supposed to function as a channel
for salt. The protein doesn’t gate
properly, so it doesn’t move salt.”
The consequence of that blockage
is mucus. It builds up in the lungs,
sinuses, and pancreas. Food doesn’t
absorb, the lungs clog. It’s difficult
to breathe. All that mucus is also an
ideal breeding ground for bacteria,
leading to frequent infections.
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Caleb’s prognosis: an average of 14
days in the hospital every six months.
“I was so afraid of germs,” Melissa
recalls. “I felt like he was going to be
the boy in the bubble.”
Still, Caleb did reasonably well on a
combination of 30-some enzymes
daily, several multivitamins, and a
couple of hours a day in a vibrating
vest designed to loosen mucus
in the lungs. It wasn’t ideal, but
Caleb managed a few years with no
hospital stays.
Then came ivacaftor.
“When I got it I was like, oh, another
med,” says Caleb. “But then it
changed my life.”
“This is the first drug approved by
the FDA that targets the genetic
defect of CF, which is that protein
abnormality,” says Dr. Sagel, who
served as the lead site investigator
for the multicenter Phase II trial
of ivacaftor, better known by its
trade name, Kalydeco. Children’s
Colorado’s Frank Accurso, M.D.,
one of the world’s foremost CF
experts, was instrumental in
developing ivacaftor.
Dr. Accurso originally served as lead
national investigator for that trial,
held at the Mike McMorris Cystic
Fibrosis Research and Care Center
at Children’s Colorado, which
proved ivacaftor to be safe and
effective.
The drug works as stand-alone
therapy for people with Caleb’s
mutation and certain other rare
mutations — currently about 8
percent of the CF population. In
2015, in combination with another
protein rescue treatment, ivacaftor
was approved for children age 12
and older who have two copies of
the most common CF mutation,
F508del. More than 10,000 people
living with CF will benefit, out of
about 70,000 worldwide.
For Caleb, the result has been
“a complete 180,” Melissa says.
His nutrient absorption and lung
function improved, and he went from
three hours a day in the vest to just
one. He was less tired and got sick
less often. His fourth grade school
attendance record was perfect.
Best of all: he plays on a basketball
team — and he’s good. “If you’d told
me a couple years ago Caleb would
be playing basketball competitively,”
Melissa says, “I would have said you
were crazy. I probably wouldn’t
even have let him.”
Caleb and Haley Nolan hash out their sibling
differences on the court.
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