Huntington's is a progressive neurodegenerative disease that affects approximately 30,000 Americans. It causes problems with muscle coordination, mental decline and dementia, with onset of symptoms typically occurring between ages 35 and 44. This condition is caused by a genetic mutation on chromosome 4, which is inherited by approximately 50 percent of offspring when only one parent carries the affected gene, according to a January 2007 article published in Lancet.
Disease Pathology
An abnormal gene carried by Huntington's patients codes for a mutant protein known as Htt, which is abundant in specific types of brain cells. Breakdown of the Htt protein generates toxic fragments thought to cause the death of brain cells. This leads to symptoms of Huntington's disease, as stated in a June 2009 article published in Science.
Gene Therapy
Scientists have developed a technique in which simple viruses are genetically modified to enable the insertion of genes into specific cells in the body, thereby altering their biochemistry in a cutting-edge technology known as gene therapy.
XIAP
The presence of the mutant Htt protein in brain cells activates molecules known as caspases, which degrade the protein. This generates toxic fragments, leading to premature death of these cells. The XIAP gene codes for a protein that inhibits caspase activity, thereby protecting cells from premature cell death. Scientists have shown that adding the XIAP gene to brain cells grown in Petri dishes reduces early cell death, according to Stanford University.
XIAP Gene Therapy
XIAP gene therapy was tested on rodents designed to show symptoms of Parkinson's disease, another degenerative neurological condition that has overlapping symptoms with Huntington's disease. This treatment significantly reduced symptoms of Parkinson's disease in these animals, and scientists are confident that similar ongoing experiments performed using rodent models of Huntington's disease will be just as successful, as stated in a September 2008 article published in Genetic Engineering and Biotechnology News.
GDNF Gene Therapy
In breakthrough gene therapy research, a modified virus was used to deliver a naturally occurring molecule called GDNF into the brain of mice that have been genetically engineered to show symptoms of Huntington's disease. These mice showed symptoms such as loss of movement control and abnormal gaits.
Treatment of these rodents with GDNF gene therapy led to an improvement in movement control, assessed by observing the mice walking on rotating rods. Most significantly, aggregates of Htt protein fragments in cells that are characteristic of Huntington's disease were greatly reduced in mice subject to gene therapy, according to a June 2006 article published in Proc Natl Acad Sci USA.
References
- PubMed; "Proc Natl Acad Sci USA"; Viral Delivery of Glial Cell Line-Derived Neurotrophic Factor Improves Behavior and Protects Striatal Neurons in a Mouse Model of Huntington's Disease; J. McBride et al; June 2006
- PubMed; "Lancet"; Huntington's Disease; F. Walker; Jan 2007
- PubMed; "Science"; Rhes, a Striatal Specific Protein, Mediates Mutant-Huntingtin Cytotoxicity; June 2009
- Genetic Engineering and Biotechnology News: Neurologix Licenses to Aegera' XIAP Gene for Use in Huntington's
- Huntington's Outreach Project at Stanford: XIAP Gene Therapy
