Re: Adeno-Associated Virus Is Safe Vector for Cystic Fibrosis Gene Therapy

July 30, 2003

Dr. Flotte rocks. We've been seeing him lately when we go to Gainesville. We

really like him. He gives you the straight scoop, and will sit and answer any

and all questions as long as you ask them.

He is Chairman of the Dept of Pediatrics and head of the Gene Therapy Institute.

He stays pretty busy but on Fridays he can't get anyone to meet with him so he

started having clinic on Friday afternoons to see patients. It's mostly the

healthier patients because the dieticians, nurses, social workers, etc are not

always available at the Friday afternoon clinic. But we have really enjoyed

picking his brain.

Angie (Ma to JC, 3 yo cowboy, wcf)

Adeno-Associated Virus Is Safe Vector for Cystic Fibrosis

Gene Therapy

Adeno-Associated Virus Is Safe Vector for Cystic Fibrosis Gene Therapy

By Karla GaleNEW YORK (Reuters Health) Jul 24 - Phase I trial results suggest

that recombinant adeno-associated serotype 2-based vectors (rAAV2) are safe

for cystic fibrosis (CF) gene therapy, according to a report in the July 20th

issue of Human Gene Therapy.Dr. Terence R. Flotte, of the University of

Florida, Gainesville, and colleagues, report their findings from the first

human

trial of rAAV2 expressing full-length human cystic fibrosis transmembrane

conductance regulator (tgAAVCF). Subjects were 25 volunteers, ages 15 to 43,

with

mild-to-moderate lung disease and at least one known disease-causing CFTR

mutant

allele. " The intent was to establish safety and see if we were working through

a

dose range with reasonably good transfer efficiency, " Dr. Flotte told Reuters

Health. " Clearly, there was no indication of toxicity. " That finding is

extremely important, he explained, since other viral vectors have been

associated

with significant inflammatory responses or other major toxicities.The vector

was administered to one side of the nose and to a single bronchopulmonary

segment of the right lower lobe. Antibiotic treatment was initiated 4 days

prior to

vector administration and continued until 14 days afterward.Adverse events

were common. Only one subject, however, experienced a severe adverse event

considered to be possibly related to the vector. And even in that case, the

episode

was similar to three previous events that occurred in the 3 months prior to

study entry. One subject exhibited transient shedding of vector in sputum, but

otherwise there was no viral shedding in urine, stool or sputum.Gene transfer

was documented in 6 subjects receiving the highest doses (more than 10 million

replicating units).The researchers observed no physiologic effect as measured

by nasal transepithelial potential difference, which Dr. Flotte described as a

" back-up test commonly used after the sweat test and genotyping in diagnosing

CF. " It could be that similar testing performed in the lower airways would

show more evidence, but such testing is technically difficult, he said. But

trials conducted by other groups suggest at least short-term clinical benefit,

he

added.Dr. Flotte noted that his group's findings support continued development

of tgAAVCF for gene transfer. In fact, he pointed out, the rAAVR2 vector " will

probably work even better in other types of tissue, such as skeletal muscle,

the retina and the brain " for delivering gene therapy.His group is currently

enrolling up to 200 CF patients at 11 sites for a randomized, control trial,

in

which tgAAVCF will be administered as an aerosol.Hum Gene Ther 2003;14:00-00.

Becki

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July 30, 2003

Hey, we see Flotte on Friday clinics in Gainesville too. :-) We love him

so much we drive 2 hours from Oviedo to see him.

My son also has alpha-1-antitrypsin deficiency and Dr. Flotte is also an

expert in the lung effects of it. He was absolutely the nicest when we

got 's bloodwork back that suggested he might have alpha-1 (this

was after we knew he had CF). He spent an hour on the phone with me

talking about all of the possibilities and what they meant, and I had

just picked his number off of the Alpha One Foundation website and

called him out of the blue.

I've also seen Drs. Faro, Wagner, and Spencer once each, and liked them

all, too.

)O(

mama to , 2yo, w/CF, and , 4yo, no CF

Re: Adeno-Associated Virus Is Safe Vector for

Cystic Fibrosis Gene Therapy

Dr. Flotte rocks. We've been seeing him lately when we go to

Gainesville. We really like him. He gives you the straight scoop, and

will sit and answer any and all questions as long as you ask them.

He is Chairman of the Dept of Pediatrics and head of the Gene Therapy

Institute. He stays pretty busy but on Fridays he can't get anyone to

meet with him so he started having clinic on Friday afternoons to see

patients. It's mostly the healthier patients because the dieticians,

nurses, social workers, etc are not always available at the Friday

afternoon clinic. But we have really enjoyed picking his brain.

Angie (Ma to JC, 3 yo cowboy, wcf)

<http://us.adserver.yahoo.com/l?M=259538.3625325.4914071.1261774/D=egrou

pmail/S=:HM/A=1695348/rand=642376971>

July 31, 2003

,

We drive 2.5 hours from above Tallahassee. We've seen most of the drs. there at

least one time. When we went Tuesday mornings we almost always saw Cheserown or

Wagner (they're ok, just not the same caliber as Flotte and Spencer). We

started going in the afternoons just so we could see some of the other drs.

Then the Friday clinics started with Flotte. I guess we've been on Fridays

three times now. Twice with Flotte and once with Sherman, who is pretty cool

too. He has 7 or 8 kids and lives on a farm. He was really good with JC. We

like Spencer alot too.

Maybe we'll run into you sometime at Shands.

Angie (Ma to JC, 3yo, wcf)