Nasal treatment targets Parkinson’s disease at its roots
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.