Featured Research

from universities, journals, and other organizations

One Shot Of Gene Therapy Spreads Through Brain In Animal Study

Date:
October 10, 2007
Source:
Children's Hospital of Philadelphia
Summary:
By targeting a site in a mouse brain well connected to other areas, researchers successfully delivered a beneficial gene to the entire brain -- after one injection of gene therapy. If these results in animals can be realized in people, researchers may have a potential method for gene therapy to treat a host of rare but devastating congenital human neurological disorders.

By targeting a site in a mouse brain well connected to other areas, researchers successfully delivered a beneficial gene to the entire brain--after one injection of gene therapy. If these results in animals can be realized in people, researchers may have a potential method for gene therapy to treat a host of rare but devastating congenital human neurological disorders, such as Tay-Sachs disease.

"After a single injection, this technique succeeded in correcting diseased areas throughout the brain," said study leader John H. Wolfe, V.M.D., Ph.D., a neurology researcher at The Children's Hospital of Philadelphia and a professor of pathology and medical genetics at the Penn School of Veterinary Medicine. "This may represent a new strategy for treating genetic diseases of the central nervous system."

Wolfe and Penn graduate student Cassia N. Cearley performed the study in mice specially bred to have the neurogenetic disease mucopolysaccharidosis type VII (MPS VII). In people, MPS VII, also called Sly syndrome, is a rare, multisystem disease causing mental retardation and death in childhood or early adulthood.

Sly syndrome is one of a class of some 60 disorders called lysosomal storage diseases that collectively cause disabilities in about one in 5,000 births. Those diseases account for a significant share of childhood mental retardation and severe, often fatal, disabilities. In each of the lysosomal storage diseases, a defect in a specific gene disrupts the production of an enzyme that cleans up waste products from cells. Cellular debris builds up within cell storage sites called lysosomes, and the waste deposits interfere with basic cell functions. Other examples of lysosomal storage diseases are Tay-Sachs disease, Hunter disease and Pompe disease.

In some types of the lysosomal storage disorder Gaucher disease, physicians can supply the missing enzyme to patients and successfully relieve disease symptoms. However, for Sly syndrome and most other lysosomal storage diseases, enzyme replacement, when available, is not very effective in treating the brain component of the disease. "Enzymes delivered to the circulation do not cross the blood-brain barrier very well," said Dr. Wolfe.

Therefore, some strategies for treating these diseases have focused on gene therapy--delivering DNA sequences that can enter cells and produce the needed enzyme. Researchers have also sought to deliver gene therapy directly to the brain rather than to the bloodstream, but there are practical limitations to making multiple injections into a child's brain.

In the current study, Wolfe targeted a particular region of the mouse brain called the ventral tegmental area (VTA), which has numerous connections with the rest of the brain. He used a neutralized virus called adeno-associated virus (AAV) as a vector--the delivery vehicle for the gene that carries coded instructions to produce the desired enzyme.

"We found that one subtype of AAV was particularly effective for transporting the gene," said Wolfe. "The neural pathways carried the virus throughout the brain, where the gene produced the enzyme. The enzyme then cleaned up the storage lesions to the point that these storage lesions were indistinguishable from those found in the brains of normal mice." One advantage of lysosomal enzymes, said Wolfe, is that cells receiving the delivered gene secrete beneficial enzymes to neighboring cells, creating a "sphere of correction."

The level of correction resulting from a single injection was "unprecedented," said Wolfe, but he cautioned that direct human treatments might be years away. In future studies, he will investigate whether this technique is effective in animals larger than mice. Such results might conceivably resemble a 2005 study in which Wolfe used gene therapy to successfully treat another lysosomal storage disease, called alpha-mannosidosis, in cats. In that study, a treated cat showed dramatic improvement in walking, compared to an untreated cat with the disease.

If the animal results can be successfully extrapolated to humans, Wolfe estimates that 2 milliliters of injected gene therapy might treat a one-year-old child. That amount might be administered with a reasonably limited number of injections, he added, although a great deal of work would be needed to reach that goal.

Researchers from The Children's Hospital of Philadelphia and the University of Pennsylvania reported their findings in the September 12 issue of the Journal of Neuroscience.

Grants from the National Institutes of Health supported this research.


Story Source:

The above story is based on materials provided by Children's Hospital of Philadelphia. Note: Materials may be edited for content and length.


Cite This Page:

Children's Hospital of Philadelphia. "One Shot Of Gene Therapy Spreads Through Brain In Animal Study." ScienceDaily. ScienceDaily, 10 October 2007. <www.sciencedaily.com/releases/2007/10/071008183301.htm>.
Children's Hospital of Philadelphia. (2007, October 10). One Shot Of Gene Therapy Spreads Through Brain In Animal Study. ScienceDaily. Retrieved September 1, 2014 from www.sciencedaily.com/releases/2007/10/071008183301.htm
Children's Hospital of Philadelphia. "One Shot Of Gene Therapy Spreads Through Brain In Animal Study." ScienceDaily. www.sciencedaily.com/releases/2007/10/071008183301.htm (accessed September 1, 2014).

Share This




More Health & Medicine News

Monday, September 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
New Drug Could Reduce Cardiovascular Deaths

New Drug Could Reduce Cardiovascular Deaths

Newsy (Aug. 30, 2014) The new drug from Novartis could reduce cardiovascular deaths by 20 percent compared to other similar drugs. 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