Featured Research

from universities, journals, and other organizations

Gene Therapy Animal Study Offers Hope For Some Neurodegenerative Diseases

Date:
September 16, 1998
Source:
University Of California, San Francisco
Summary:
A study co-authored by UC San Francisco researchers offers the first evidence that a gene therapy technique involving ribozymes, molecules that disrupt protein production, can be used to slow neurodegeneration in an animal model, signalling a possible approach for overcoming one of the monumental hurdles of gene therapy.

A study co-authored by UC San Francisco researchers offers the first evidence that a gene therapy technique involving ribozymes, molecules that disrupt protein production, can be used to slow neurodegeneration in an animal model, signalling a possible approach for overcoming one of the monumental hurdles of gene therapy.

In the study, reported in the August issue of Nature Medicine, researchers demonstrated that ribozymes could be used to reduce the production of a faulty gene product that leads to the degeneration of light-sensitive rod cells in the eye. The degeneration occurs in association with autosomal dominant retinitis pigmentosa, an untreatable condition of progressive blindness.

Importantly, the approach could potentially also be used to treat other diseases resulting from a destructive protein, including some forms of glaucoma, Huntington's disease, amyotrophic lateral sclerosis (ALS) and Warfan's syndrome, according to the senior author of the study, Matthew M. LaVail, PhD, a professor of anatomy and ophthalmology at UCSF.

The finding represents an important breakthrough in the still fledgling field of gene therapy, which has been particularly challenged by disorders caused by abnormal, or mutant, proteins, so-called autosomal dominant diseases, said LaVail.

Most gene therapy approaches have focused on diseases that occur when the two copies of a particular gene fail to produce, or fail to produce sufficient quantity of, a healthy protein. The challenge in developing treatments for these so-called autosomal recessive diseases, such as cystic fibrosis, has involved trying to introduce healthy genes directly into the pertinent cells to replace and compensate for the missing proteins. This challenge has been daunting enough. Some successes have been achieved in animal models with recessive diseases, but only in recent months have such approaches even begun to demonstrate small successes in clinical trials, according to LaVail.

But researchers have been virtually foiled in their attempts to create a gene therapy technique for diseases in which one of the two copies of a gene produces a protein that is actually destructive, as is the case with autosomal dominant diseases.

"That's what makes this study particularly exciting," said LaVail. "The research community has been really stumped when it comes to developing gene therapy techniques that will destroy faulty gene products to a clinically relevant degree. Scientists have thought that ribozymes would prove to be an effective approach, and our study establishes that they are."

In the study, conducted in rats, the DNA containing the code for specifically designed ribozymes was carried via a harmless adeno-associated virus vector. The researchers injected the DNA-containing vectors immediately adjacent to the rod cells of the eyes. Once the vectors infected the rod cells, the DNA synthesized the ribozymes, short strands of RNA, which were "turned on" by a promoter molecule that is active only in rod cells.

The ribozymes, one shaped like a hairpin, the other like a hammerhead, then sought out and destroyed the faulty messenger RNA carrying the mutated gene's code for building the destructive protein.

The results were significant: After two to three months, 30 to 40 percent more rod cells remained in eyes that had been injected with either of the ribozymes than in eyes receiving placebo injections.

"We've demonstrated the effectiveness of these approaches by direct measurement of the reduction of the mutant RNA in the retina, in studies of the eye's anatomy and in the ability of the eye to show better electrical function following therapy," said LaVail.

Phase I clinical trials of the therapy could begin within several years if subsequent studies prove the method safe and effective.

The co-authors of the study included Alfred S. Lewin, Kimberly A. Drenser and William W. Hauswirth of the University of Florida College of Medicine, Shimpei Nishikawa, MD, PhD, a visiting postdoctoral fellow at UCSF, Douglas Yasumura, MA, a specialist at UCSF, and John G. Flannery, of UC Berkeley.

The study was funded by grants from the National Eye Institute, The Foundation Fighting Blindness, Research to Prevent Blindness, That Man Might See, Inc., and the March of Dimes Foundation.


Story Source:

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


Cite This Page:

University Of California, San Francisco. "Gene Therapy Animal Study Offers Hope For Some Neurodegenerative Diseases." ScienceDaily. ScienceDaily, 16 September 1998. <www.sciencedaily.com/releases/1998/09/980916074145.htm>.
University Of California, San Francisco. (1998, September 16). Gene Therapy Animal Study Offers Hope For Some Neurodegenerative Diseases. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/1998/09/980916074145.htm
University Of California, San Francisco. "Gene Therapy Animal Study Offers Hope For Some Neurodegenerative Diseases." ScienceDaily. www.sciencedaily.com/releases/1998/09/980916074145.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) — A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
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