Data presented for the first time on Monday at the XIInternational Congress Meeting on Cystic Fibrosis in Dublin,Ireland, appears to hold promise for the development of non-toxic, gene-based drugs to treat cystic fibrosis.

Cystic fibrosis is a fatal recessive genetic disease that causesrespiratory infections, leading to breathing difficulties, lungdamage and digestive problems.

A research team that included scientists from Cambridge,Mass.-based Genzyme Corp., led by Jeff Whitsett of Children'sHospital Medical Center in Cincinnati, reported on studies intransgenic mice showing that expression of cystic fibrosistransmembrane conductance regulator (CFTR) protein duringlung growth and development was not harmful.

Data also suggested that even high doses of CFTR can be safelytransferred to lung epithelial cells of cystic fibrosis patients forgene or protein replacement therapy.

"It appears that we can put CFTR into lungs of animals in anon-cell specific fashion despite the fact that it's beingexpressed in high levels and in some cells which don't normallyexpress the protein," said Richard Gregory, senior scientist withGenzyme.

Gregory said that the findings are important to support genetherapy and protein replacement as possible treatments forcystic fibrosis.

"We needed to know what would happen if we overdosed theprotein," Gregory said.

In a separate study, Alan Smith, Genzyme's senior vicepresident of research, reported for the first time on datasupporting the idea that cystic fibrosis is caused by themislocalization of the CFTR protein. These findings havesuggested a third approach to the company's portfolio of cysticfibrosis therapies: developing drugs to reposition CFTR to itscorrect location.

David Stone, an analyst with Cowen and Co. in Boston, pegs themarket for treating or diagnosing cystic fibrosis in excess of$500 million, based on a patient market of 30,000 in both theU.S. and the United Kingdom. Stone said the study resultsrepresent "another step toward realizing what could beGenzyme's largest product opportunity."

In addition, Genzyme subsidiary IG Laboratories Inc. reportedthat its CF/12 Cheek Brush Test to detect carriers or todiagnose cystic fibrosis will be available by the end of the year.

The test, which replaces the traditional method of gatheringcells from a blood sample, is performed on cells obtained bybrushing the inside of the cheek, and will be able to identify 12of the most common mutations associated with cystic fibrosis.Polymerase chain reaction (PCR) technology is used to amplifyCFTR gene segments in each sample simultaneously for 12mutations before analysis.

The cheek test is less-expensive than traditional cystic fibrosisblood tests because it can rapidly analyze samples, according toBarbara Handelin, director of molecular and specialty geneticsat IG Labs. She said that a blood sample may test a range ofmutations from as few as four to as many as 12, and addedthat Vivigen Inc. of Santa Fe, N.M., has a blood test in thepipeline that will test as many as 14 mutations. According toHandelin, IG Laboratories intends to acquire Vivigen.

Handelin declined to discuss predicted sales for the CF/12cheek test. However, Stone said that at $100 per test, the cost issomewhat less than competing methods of analysis, whichHandelin placed at between $150 and $275 per sample. Stoneadded that the cheek test appears to be an efficient method ofDNA analysis.

"The social and public health issues surrounding DNA carriertesting have a long way to go, and must answer the question,What does the result of such a test mean for the averageperson?" said Handelin. "But if social issues were settled, thiswould be a reasonably cost-effective and technically feasiblemeans for any large-scale DNA testing."

The Office of Technology Assessment, a research arm ofCongress, issued a report earlier this month about screening forcarriers of CF. According to the report, as many as 8 millionpeople in the U.S. could be identified as CF carriers.

"Since 1989, clinicians have been able to use DNA tests toidentify CF carriers before they have a child with CF -- four offive individuals with CF are born to couples with no familyhistory of the illness," the report said. "Today's DNA test caninform individuals and couples about their risk of having achild with CF, but it is not 100 percent sensitive, nor likely everto be."

The OTA report said the prospect of large-scale screening for CFprompted the House of Representatives to ask the OTA toassess the scientific, legal, economic and social implications ofCF carrier screening.

Genzyme's CF research is supported by Neozyme II Corp., whichGenzyme founded last March to fund development ofbiotherapeutic products to treat the disorder using proteinreplacement and gene therapy. Genzyme declined to say whenit expected to enter clinical trials with a CF gene therapy.However, an Oppenheimer & Co. report this month said thatGenzyme's trials were in the same time frame as a competitor's,Genetic Therapy Inc., which planned to start trials sometimebefore mid-1993.

Genzyme's stock (NASDAQ:GENZ) closed Monday at $40.50 ashare, down $1.50.

-- Michelle Slade Associate Editor

(c) 1997 American Health Consultants. All rights reserved.

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