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To: Jongmans who started this subject	1/4/2002 9:49:24 AM
From: nigel bates	of 53

Cloned sheep Dolly develops arthritis LONDON, Jan 4 (Reuters) - Dolly, the world's first cloned sheep, has developed arthritis, raising fears that the cloning process may have given her a genetic defect. Professor Ian Wilmut of the Roslin Institute in Scotland said on Friday that Dolly, the first mammal cloned from a cell taken from an adult animal, had arthritis in her left hind leg. Arthritis is not unknown in sheep but Dolly, born in 1996, has developed it at an unusually young age, suggesting it may be the result of a genetic defect, possibly caused by cloning. "The fact that Dolly has arthritis at this comparatively young age suggests that there may be problems," Wilmut told BBC radio. Cloning is a hot area of medical research. Rival teams this week announced the birth of cloned, genetically engineered pigs that may be suitable for animal-to-human transplants. Wilmut said it was too early to draw conclusions from Dolly's case, and he urged biotech companies and research laboratories to share information about the health of their cloned animals to see if there was a common thread. "We know already there is an unusual incidence of death in cloned animals around the time of birth. What we need to go on studying is whether diseases like arthritis, which tend to be associated with older age, occur in a normal way or whether the incidence is changed," he said. Researchers at PPL Therapeutics Plc (LSE: PTH.L) , which helped to produce Dolly, and a U.S. joint venture company set up by Novartis AG and BioTransplant Inc have both recently cloned pigs whose organs may be compatible with humans...

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To: Jongmans who started this subject	8/24/2002 8:10:55 AM
From: Jongmans	of 53

Advance in cloning propels biotech firm Naomi Aoki The Boston Globe Saturday, August 24, 2002 PPL Therapeutics PLC has said it cloned piglets lacking both copies of a gene responsible for triggering a violent immune response in humans, advancing long-held hopes for growing a supply of organs available for transplant to people. The announcement, made Thursday, appears to put PPL Therapeutics, the British company that helped clone Dolly the sheep in 1997, ahead of Immerge BioTherapeutics Inc. of Charlestown, Massachusetts, in the race to be the first to create a safe pool of donor organs from pigs. Within days of each other in January, the two companies announced that they had cloned pigs whose DNA was altered to "knock out" one of the pair of alpha-1-galactose genes. The gene produces a coating of sugar on the surface of pig cells, which causes the human immune system to reject pig tissue and organs. Immerge, a joint venture of Novartis Pharma AG and Biotransplant Inc., said its efforts to knock out both copies of the gene were "proceeding well." But PPL is the first to publicly announce that it has successfully cloned the "double knockout" pigs. Four healthy piglets were born on July 25. A fifth piglet died of unknown causes shortly after birth, the company said. "This advance brings us closer to the promise of a potential solution to the worldwide shortage of organs and cells for transplantation," said David Ayares, chief operating officer and vice president for research at PPL's U.S. subsidiary in Virginia, where the pigs were cloned. For nearly two decades, scientists have been studying pigs as a potential source of organs for humans. Surprisingly enough, pigs are biologically similar to people and carry fewer deadly diseases than primates. But the research has been riddled with setbacks. Chief among them has been the powerful attack mounted by the body's immune system against foreign invaders - a natural defense that causes an almost immediate rejection of animal organs. But advances in recent years have breathed new life into the field, known as xenotransplantation. At least six labs have been searching for a way to manipulate pigs so their organs could be used for human transplants. Analysts predict the market could generate billions of dollars for companies that succeed in the quest. Nearly 80,000 people are on waiting lists, thousands more with ailing organs do not make the lists, and 16,000 people die each year in the United States alone while they wait. "Developing another source of organs would have a profound impact on society, so from a practical perspective this is a very important advance," said Dr. Jeffrey Platt, head of transplantation biology at the Mayo Clinic in Minnesota. In a matter of weeks, Ayares said, PPL scientists will begin transplanting cells from the young piglets into primates. If the cells are not rejected and survive for more than 90 days, the company plans to seek regulatory approval to transplant insulin-producing cells into humans as a potential treatment for diabetes. "It's conceivable that in the next two years we could start human clinical trials," Ayares said. The transplantation of whole organs is likely to be further away and require additional genetic modification. Other questions remain. Pigs also carry a potentially harmful virus, known as porcine endogenous retrovirus, or PERV. Although the virus has never been transmitted to humans, it raises concerns about the risk of infection. Shares of PPL rose 0.25 pence to 7.5 pence (11.4 cents) in midday Friday trading, adding to the 0.5 pence gain Thursday as 6 million shares traded, more than 30 times the average daily volume. iht.com martin

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To: Jongmans who started this subject	1/22/2003 9:58:39 PM
From: John McCarthy	of 53

Originally published in Science Express as 10.1126/science.1078942 on December 19, 2002 Science, Vol. 299, Issue 5605, 411-414, January 17, 2003 Production of 1,3-Galactosyltransferase-Deficient Pigs Carol J. Phelps,1 Chihiro Koike,34 Todd D. Vaught,1 Jeremy Boone,1 Kevin D. Wells,1 Shu-Hung Chen,1 Suyapa Ball,1 Susan M. Specht,34 Irina A. Polejaeva,1 Jeff A. Monahan,1 Pete M. Jobst,1 Sugandha B. Sharma,34 Ashley E. Lamborn,1 Amy S. Garst,1 Marilyn Moore,2 Anthony J. Demetris,35 William A. Rudert,36 Rita Bottino,36 Suzanne Bertera,36 Massimo Trucco,36 Thomas E. Starzl,34 Yifan Dai,1* David L. Ayares1* The enzyme 1,3-galactosyltransferase (1,3GT or GGTA1) synthesizes 1,3-galactose (1,3Gal) epitopes (Gal1,3Gal1,4GlcNAc-R), which are the major xenoantigens causing hyperacute rejection in pig-to-human xenotransplantation. Complete removal of 1,3Gal from pig organs is the critical step toward the success of xenotransplantation. We reported earlier the targeted disruption of one allele of the 1,3GT gene in cloned pigs. A selection procedure based on a bacterial toxin was used to select for cells in which the second allele of the gene was knocked out. Sequencing analysis demonstrated that knockout of the second allele of the 1,3GT gene was caused by a T-to-G single point mutation at the second base of exon 9, which resulted in inactivation of the 1,3GT protein. Four healthy 1,3GT double-knockout female piglets were produced by three consecutive rounds of cloning. The piglets carrying a point mutation in the 1,3GT gene hold significant value, as they would allow production of 1,3Gal-deficient pigs free of antibiotic-resistance genes and thus have the potential to make a safer product for human use. 1 PPL Therapeutics Inc., 1700 Kraft Drive, Blacksburg, VA 24060, USA. 2 PPL Therapeutics Ltd., Roslin, Midlothian, EH25 9PP, UK. 3 Thomas E. Starzl Transplantation Institute, 4 Department of Surgery, 5 Department of Pathology, and 6 Department of Pediatrics (Division of Immunogenetics) of University of Pittsburgh Medical Center (UPMC) and Children's Hospital, Pittsburgh, PA 15213, USA. * To whom correspondence should be addressed. E-mail: ydai@ppl-therapeutics.com; dayares@ppl-therapeutics.com druglinx.com John McCarthy

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