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:2/1/2016)... 1, 2016 Rising sales of ... global touchfree intuitive gesture control market size ... sales of consumer electronics coupled with new technological advancements ... size through 2020   --> ... new technological advancements to drive global touchfree intuitive gesture ...
(Date:2/1/2016)... ( www.wocketwallet.com ) announces the launch of a new video featuring singer, ... Las Vegas , where Joey appeared at the Wocket booth to ... , where Joey appeared at the Wocket booth to meet and greet ... the Consumer Electronics Show (CES2016) in Las Vegas , ... --> --> The video is ...
(Date:1/27/2016)... Jan. 27, 2016  Rite Track, Inc. a leading ... West Chester, Ohio announced today the ... staff, based in Austin, Texas , ... to provide modifications, installations and technical support offerings for ... of PLUS, commented, "PLUS has provided world class service ...
Breaking Biology News(10 mins):
(Date:2/8/2016)... -- --> --> ... ultra-rapid Point-Of-Care (POC) molecular diagnostics company, today announces that it ... test to be launched on the Company,s io® platform. By ... test is now cleared for sale within the European Union. ... of the io® CT test signals a new era in ...
(Date:2/5/2016)... 2016  In the pharmaceutical industry the medical affairs ... launch activities including the identification and engagement of key ... especially high in the oncology therapeutic area where most ... the Role of Medical Affairs in Oncology Launch Excellence ... therapies find better ways to utilize medical affairs to ...
(Date:2/4/2016)... ... February 04, 2016 , ... ... and compliance training, today announced an interactive FDA compliance training course, ... RAPS (Regulatory Affairs Professional Society) accredited interactive course on Morf Playbook—now conveniently available ...
(Date:2/4/2016)... ... February 04, 2016 , ... ... Digital Forensics Club, takes place February 5-6 at the University’s student center, ... and activities such as workshops and competitions for ample networking, learning and ...
Breaking Biology Technology: