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Alzheimer's and Parkinson's Disease Treatment May Involve Gene Therapy - UCLA Researchers Found KCNC3 Gene Mutation

February 26th 2006

Alzheimer's and Parkinson's Disease Treatment May Involve Gene Therapy - UCLA Researchers Found KCNC3 Gene Mutation

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Researchers in Los Angeles believe they have linked a gene mutation that regulates how potassium enters cells to a neurodegenerative disease and to another disorder that causes mental retardation and coordination problems.  This discovery may lead to treatments for Alzheimer’s and Parkinson’s diseases. 

The movement disorder called spinocerebellar ataxia, usually appears in adulthood and causes loss of neurons in the brain's cerebellum, resulting in progressive loss of coordination (ataxia).  According to Dr Stefan Pulst "This type of gene has never before been linked to nerve cell death."  Dr. Pulst, of Cedars-Sinai Medical Center at the University of California, Los Angeles, led the new study. 

Dr. Pulst and his colleagues looked for the gene that caused the neurodegenerative movement disorder spinocerebellar ataxia in a Filipino family.  They believe the gene called KCNC3 may have something to do with ataxia. 


The KCNC3 gene codes for one of the proteins that form potassium channels.  These channels are pore-like openings in the cell membrane that control the flow of potassium ions into the cell.  Previous research identified a different KCNC3 mutation in a French Family with spinocerebellar ataxia type 13, which causes childhood-onset ataxia, cerebellar degeneration, and mild mental retardation.

The KCNC3 gene codes for a type of potassium channel that opens and closes very quickly.  This channel is important in fast-bursting neurons that fire hundreds of times per second in the brain.  Dr. Pulst said "Fast-bursting neurons are like building blocks – they are used in the nervous system a lot." 

Dr. Pulst said these channels also aid the motor control area of the brain called the substantia nigra, and the hippocampus where they play a role in learning.  Earlier studies found abnormalities in the number of potassium channels in Parkinson's, Alzheimer's, and Huntington's diseases.  It is possible the potassium channel abnormalities may contribute to a wide variety of neurodegenerative diseases.


The gene mutations in the Pilipino and French families affected the potassium channels very differently.  The researchers found the mutation found in the Filipino family completely prevented the potassium channel from functioning, while the mutation in the French family caused the channels to open earlier than normal and close later. This reduced the rate at which the neurons could fire.

The potassium channel genes have also been linked to epilepsy, cardiac arrhythmias, and periodic muscle paralysis..  One potassium channel defect has also been found in a disorder called episodic ataxia type 1 that causes brief episodes of ataxia without neurodegeneration. 

The unexpected finding was that the potassium channel defect may be linked to neurodegenerative disease or mental retardation.  This was unexpected because in mice studies, the KCNC3 gene have only mild behavioral changes.


The research may lead to drugs that alter the activity of potassium channels.  Dr. Pulst said in order to maximize the benefits and reduce side effects; researchers would need to find drugs that are specific for this type of channel.

Funding for the study came in part from National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS).  Dr. Katrina Gwinn-Hardy, M.D., the NINDS program director for the research said "This paper is a good example of how gene discovery is useful for giving clues about therapeutic targets and strategies, which is the most important goal of human gene discovery research in my view." 
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