Navigation Links
Caltech researchers show efficacy of gene therapy in mouse models of Huntington's disease
Date:10/30/2009

Pasadena, Calif.Researchers at the California Institute of Technology (Caltech) have shown that a highly specific intrabody (an antibody fragment that works against a target inside a cell) is capable of stalling the development of Huntington's disease in a variety of mouse models.

"Gene therapy in these models successfully attenuated the symptoms of Huntington's disease and increased life span," notes Paul Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences.

Patterson is the senior investigator on the study, which was published in the October 28 issue of the Journal of Neuroscience.

Huntington's disease is a neurodegenerative disorder with a genetic basis. The disorder has its roots in a mutation in a protein called huntingtin, or Htt. (The gene itself is also referred to as the huntingtin gene.)

All versions of the Htt gene have repeats of a particular trio of nucleotidesspecifically, C, A, and G, which together code for the amino acid glutamine. In most people, that trio is repeated between 10 and 35 times. But in people who develop Huntington's disease, that genetic stutter goes on and on; they will have anywhere between 36 to upwards of 120 repeats.

The result of all these repeats? An abnormally long version of the Htt protein, which gets chopped up into smaller, toxic pieces and accumulates in nerve cells, debilitating them.

Enter Patterson group members Amber Southwell and Jan Ko, who began to look at the efficacy of two different intrabodies that had been shown, in cell cultures and fruit-fly models, to reduce the accumulation of toxic Htt protein. To see whether those effects would hold true in mammalian systems as well, the team tested the intrabodies in a series of five different mouse models of Huntington's.

One of the two intrabodies had some negative results, actually increasing Huntington's-related mortality in one model.

But the other intrabodycalled Happ1was an unqualified success, restoring motor and cognitive function to the mice, and reducing neuron loss as well as toxic protein accumulation. And in one model, it increased both body weight and life span.

Happ1 targets an amino-acid sequence unique to the Htt protein that is rich in the amino acid proline. Because of this, the action of Happ1 is expected to be extremely specific. "Our studies show that the use of intrabodies can block the parts of mutant huntingtin that cause its toxicity without affecting the wildtype, or normal, huntingtinor any other proteins," says Patterson. In other words, he says, this has the potential to be the kind of "silver-bullet therapy" that many medical researchers look for.

This sort of research is of particular importance in the treatment of Huntington's disease, says Patterson. Despite the fact that this disorder has a single-gene origin, current treatments tend to address the symptoms of the disease, not its cause. That means it is currently impossible to prevent the disease from doing significant damage in the first place.

What's the next step in pursuit of this goal? "We need to improve the efficacy of the intrabody," Patterson says, "and we need to build a viral vector that can be controlledinduced and turned offin case of unexpected side effects. This is a general goal shared by all types of experimental gene therapies."


'/>"/>

Contact: Lori Oliwenstein
lorio@caltech.edu
626-395-3631
California Institute of Technology
Source:Eurekalert

Related biology news :

1. Caltech scientists create robot surrogate for blind persons in testing visual prostheses
2. Caltech scientists get detailed glimpse of chemoreceptor architecture in bacterial cells
3. Caltech neuroscientists find brain region responsible for our sense of personal space
4. Caltech researchers explore how cells reconcile mixed messages in decisions about growth
5. Caltech scientists reveal how neuronal activity is timed in brains memory-making circuits
6. Caltech scientists show why anti-HIV antibodies are ineffective at blocking infection
7. Caltech scientists control complex nucleation processes using DNA origami seeds
8. Caltech researchers train computers to analyze fruit-fly behavior
9. Caltech and UCSD researchers shed light on how proteins find their shapes
10. Caltech researchers help unlock the secrets of gene regulatory networks
11. Caltech researchers get first look at how groups of cells coordinate their movements
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/10/2016)... BLUE BELL, Pa. , March 10, 2016   ... U.S. Customs and Border Protection (CBP) is testing ... in San Diego to help identify ... United States . The test, designed to help determine ... outdoor, pedestrian environment, began in February and will run until ...
(Date:3/9/2016)... 2016 Nigeria . ... than 23,000 public service employees either did not exist ... salary unlawfully.    --> Nigeria ... more than 23,000 public service employees either did not ... their salary unlawfully.    --> DERMALOG, the ...
(Date:3/8/2016)... N.C. , March 8, 2016   ... sensor technology, today announced it has secured $11M ... by GII Tech, a new venture fund being ... with additional participation from existing investors TDF Ventures ... the funds to continue its triple-digit growth and ...
Breaking Biology News(10 mins):
(Date:4/29/2016)... ALBANY, New York , April 29, 2016 ... market report published by Transparency Market Research "Separation ... Analysis, Size, Share, Growth, Trends, and Forecast 2015 ... market was valued at US$ 10,665.5 Mn in ... CAGR of 6.8% from 2015 to 2023 to ...
(Date:4/29/2016)... ... 2016 , ... Intelligent Implant Systems announced today that the two-level components for ... the United States. These components expand the capabilities of the system and allow ... in October of 2015, the company has seen significant sales growth in 1Q 2016, ...
(Date:4/28/2016)... 28, 2016 Q BioMed ... Company,s CEO  was featured in an article he ... VCs Fear To Tread: http://www.lifescienceleader.com/doc/accelerators-enter-when-vcs-fear-to-tread-0001 ... is an essential business journal for life ... biotechs to Big Pharmas. Their content is designed ...
(Date:4/28/2016)... NY (PRWEB) , ... April 28, 2016 , ... ... has made significant investments in recruiting top industry experts, and expanding its LATAM ... which provides industry-leading tools for clients to manage their clinical trial projects. , ...
Breaking Biology Technology: