Featured Research

from universities, journals, and other organizations

Gene Therapy Treats First Disease Affecting Multiple Organ Systems In A Large Animal

Date:
September 10, 2002
Source:
University Of Pennsylvania
Summary:
For the first time, researchers have successfully used gene therapy to treat a disease that affects organs throughout the body of a large animal. The results will be reported this week on the Web site of the Proceedings of the National Academy of Sciences.

PHILADELPHIA -- For the first time, researchers have successfully used gene therapy to treat a disease that affects organs throughout the body of a large animal. The results will be reported this week on the Web site of the Proceedings of the National Academy of Sciences. The study, led by Mark E. Haskins of the University of Pennsylvania School of Veterinary Medicine and Katherine Parker Ponder of Washington University School of Medicine in St. Louis, involved dogs with a rare disorder in which an enzyme deficiency causes clouding of the corneas, cardiac disease and bone abnormalities leading to loss of mobility by six months of age. Newborn dogs treated with hepatic gene therapy maintained near-normal mobility throughout the 17-month study and showed little evidence of the other debilitating signs normally associated with the disease.

"While gene therapy has been used previously in dogs, this is the first use to treat a disorder affecting multiple organ systems throughout the body," said Haskins, professor of pathology and medical genetics at Penn. "Previous applications of gene therapy in dogs have targeted disorders affecting a single bodily function, such as vision or blood clotting. Like many diseases that we might eventually like to treat with gene therapy, this one has complex, multisystemic effects."

The experiments involved seven dogs with mucopolysaccharidosis VII, a disorder in which the enzyme beta-glucuronidase is deficient in activity. Also known as Sly syndrome, MPS VII is among a constellation of lysosomal storage diseases; in humans, such disorders include Tay Sachs disease and Gaucher disease.

"In theory, the approach should be applicable to other lysosomal storage diseases, with the exception of those that affect the central nervous system," said Ponder, associate professor of medicine and assistant professor of biochemistry and biophysics at Washington University. "We're hopeful that the approach might also be applicable to hemophilia."

Lysosomal storage diseases such as MPS VII can be treated through enzyme replacement therapy, but that approach requires regular intravenous injections and is prohibitively expensive. Bone-marrow transplantation is another option but is risky, and compatible donors are often unavailable.

MPS diseases affect 1 in 27,000 live births among humans, but the disease is debilitating for patients and emotionally wrenching for their families. Human symptoms include growth retardation, mobility problems, facial deformities, corneal clouding, heart-valve and liver abnormalities and mental retardation, among others. Most patients die in childhood.

"The gene therapy research of Drs. Haskins, Ponder and collaborators involving MPS VII dogs has significant implications for all MPS disorders," said Barbara Wedehase, executive director of the National MPS Society, an organization of parents of children with MPS. "Their current and ongoing research will provide new insights into the treatment of individuals affected with these devastating disorders."

In these experiments, two- to three-day-old dogs with MPS VII received four simple intravenous injections of a retroviral vector expressing canine beta-glucuronidase. The vector used was made from the Moloney murine leukemia virus with a liver-specific promoter; at several days of age, canine liver growth is so rapid that transduction occurs readily and beta-glucuronidase is secreted continuously into the bloodstream.

The enzyme's activity was subsequently found at normal, stable levels for up to 14 months in the treated dogs; one dog has produced 60 times normal enzyme for 17 months. Unlike other dogs with MPS VII, the treated dogs gained weight normally, attaining nearly 90 percent the weight of their unaffected littermates, and avoided the serious side effects normally associated with lysosomal storage diseases. The beta-glucuronidase gene does not appear to have been inserted into the germ line.

Haskins and Ponder were joined in the research by John R. Melniczek, Margaret A. Weil, Thomas M. O'Malley, Patricia A. O'Donnell, Van W. Knox, Hamutal Mazrier, N. Matthew Ellinwood, Meg Sleeper, Susan W. Volk, Jean Zweigle and John H. Wolfe of Penn's School of Veterinary Medicine; Albert M. Maguire of Penn's School of Medicine; Lingfei Xu and Robert L. Mango of Washington University's School of Medicine; and Gustavo D. Aguirre of Cornell University's College of Veterinary Medicine. The work was funded by the National Institutes of Health.


Story Source:

The above story is based on materials provided by University Of Pennsylvania. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania. "Gene Therapy Treats First Disease Affecting Multiple Organ Systems In A Large Animal." ScienceDaily. ScienceDaily, 10 September 2002. <www.sciencedaily.com/releases/2002/09/020910080413.htm>.
University Of Pennsylvania. (2002, September 10). Gene Therapy Treats First Disease Affecting Multiple Organ Systems In A Large Animal. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2002/09/020910080413.htm
University Of Pennsylvania. "Gene Therapy Treats First Disease Affecting Multiple Organ Systems In A Large Animal." ScienceDaily. www.sciencedaily.com/releases/2002/09/020910080413.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins