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Nasal treatment targets Parkinson’s disease at its roots

Print this Page   Home > News > 2013 > Nasal treatment targets Parkinson’s disease at its roots

April 29, 2013

Author: Angela Herring

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Each year, 60,000 adults are newly diag­nosed with Parkinson's dis­ease, aneu­rode­gen­er­a­tive dis­order that causes a slew of symp­toms, includingtremors, slowed move­ments, and changes in speech. The drugs cur­rentlyavail­able to treat PD patients help them regain some of the motor con­trollost through the dis­ease, but don't treat the under­lying cause, said Bar­baraWaszczak, a pro­fessor of phar­ma­ceu­tical sci­ences in the Bouvé Col­lege ofHealth Sci­ences.

"Parkinson's is caused by the death of dopamine neu­rons in a key motorarea of the brain called the sub­stantia nigra," said Waszczak. If you want totreat PD at its roots, she added, then you have to stop the death of theseneural cells. In research reported ear­lier this week at the Exper­i­mentalBiology 2013 con­fer­ence in Boston, Waszczak and grad­uate stu­dent BrendanHarmon pro­posed a treat­ment approach that does exactly that. What's more, themethod is simple and easy to use.

A nat­u­rally pro­duced pro­tein called glial cell-​​line-​​derivedneu­rotropic factor, or GDNF, pro­tects cer­tain cells—including dopamineneurons—against death by acti­vating sur­vival and growth-​​promoting path­wayswithin, according to Waszczak. In petri dishes on the lab bench, GDNF does agreat job restoring func­tion to dam­aged and dying dopamine neu­rons andpre­venting fur­ther loss. But get­ting GDNF into the actual animal brain, whichis hard to access from the out­side, isn't so simple.

Crossing the so-​​called "blood brain bar­rier" has proved a dif­fi­cultchal­lenge for Parkinson's researchers. But in pre­vious work, Waszczak's labshowed that GDNF could be deliv­ered to the right loca­tion inside the brainthrough a simple intranasal delivery method.

For this to work, how­ever, patients would have to take GDNF repeat­edly,because it's readily broken down inside the body. In the new research, Harmontook it a step fur­ther, by trans­fecting brain cells with a gene for GDNF. "Weused a nanopar­ticle delivery system that incor­po­rates the genetic mate­rialto make GDNF into the DNA itself," said Harmon. "It's like a fac­tory,pro­ducing the pro­tein from inside the brain." Coper­nicus Ther­a­peu­ticsengi­neered the nanoparticles.

Harmon first showed that intranasal delivery of the nanopar­ti­clesincreased GDNF pro­duc­tion in the brain. Then he showed that the treat­mentcould greatly reduce the loss of dopamine neu­rons in a rat with Parkinson'sdis­ease. Now the rat's brain can essen­tially make its own medicine.

Parkinson's patients don't begin showing symp­toms until 80 to 90 per­centof their dopamine cells have died, said Waszczak. At that point, GDNF wouldhave little use. But for those recently diag­nosed with PD or thought to be ata high risk for the dis­ease, this new treat­ment rep­re­sents aneu­ro­pro­tec­tive and neu­rorestora­tive approach. "If we can get at it inthe early stages of the dis­ease, when patients are just starting to developsymp­toms, then we might be able to stop the dis­ease from get­ting worse or atleast delay the onset of severe symp­toms," Waszczak explained.

The team hopes to con­tinue its explo­ration to hone in on more nuancedques­tions, such as how often the nasal treat­ments need to be admin­is­teredand at what doses, and whether the approach works in other animal models.

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