Parkinson’s Disease Halted in Animal Subject
July 4, 2012 § 2 Comments
Parkinson’s Disease is a neurological disorder that affects millions of people worldwide. Although many effective treatments have been developed, none have proven successful in slowing its progression.
The cause of Parkinson’s is as of yet unknown, but a protein called α-synuclein is thought to be the culprit. This protein is found in all Parkinson’s patients. Its tendency to collect together in the brain forms toxic clumps that destroy brain neurons.
In an experiment published in the online edition of the journal Neurotherapeutics, scientists at UCLA have discovered a way to break up these aggregates and prevent the proteins from clumping in the first place. Jeff Bronstein, UCLA professor of neurology, along with Gal Bitan, associate UCLA professor of neurology, and their colleagues, have developed a new compound that they call a “molecular tweezer”.
The UCLA tweezer compound is able to prevent the protein clumps from forming, stop them from becoming toxic, and are also able to break up the clumps that have already accumulated, all without hampering normal brain function.
Protein aggregation is the cause of many diseases for which there is no cure. Alzheimer’s, Parkinson’s, and Type 2 Diabetes are all the result of protein aggregation. If doctors are able to prevent the clumping altogether, they can prevent these diseases from forming, without having to find a cure. The difficulty with finding a therapy that targets only protein aggregates is due to the natural ubiquity of α-synuclein all through the brain. The aggregation and toxicity of α-synuclein must be prevented, but not α-synuclein’s regular functioning. Bronstein believes this protein aids communication between neurons, but this is mere speculation.
The compound developed through the Bronstein-Bitan collaboration – CLR01 – was very successful at attacking the targeted aggregates and leaving other normal brain functions untouched. Bronstein explains, “The most surprising aspect of the work is that despite the ability of the compound to bind to many proteins, it did not show toxicity or side effects to normal, functioning brain cells.” Bitan added, “We call this unique mechanism ‘process-specific,’ rather than the common protein-specific inhibition.”
The next step for the researchers was to try the compound in a living organism. They tested it on the zebrafish. This fish is common for animal research because it can be easily genetically manipulated, develops rapidly, and it is transparent, making observation and measurement a simple task.
The researchers used a transgenic zebrafish and used fluorescent proteins to track the added CLR01’s effects on the aggregates. Indeed, the tweezer prevented α-synuclein aggregation and, by extension, neural death. This halted the progression of Parkinson’s in the live animal model. Bronstein says, “CLR01 holds great promise as a new drug that can slow or stop the progression of Parkinson’s and related disorders. This takes us one step closer to a cure.”
Researchers are currently studying the CLR01 in a mouse model of Parkinson’s. Each new animal species trial takes them one step closer to human clinical trials, along the path to finding a cure.
“Parkinson’s Disease Stopped in Animal Model”. (March 2, 2012). Neuroscience News. March 8, 2012. http://neurosciencenews.com/parkinsons-disease-stopped-animal-model-clr01/.