Nasal treatment targets Parkinson’s disease at its roots

Each year, 60,000 adults are newly diagnosed with Parkinson’s disease, a neurodegenerative disorder that causes a slew of symptoms, including tremors, slowed movements, and changes in speech. The drugs currently available to treat PD patients help them regain some of the motor control lost through the disease, but don’t treat the underlying cause, said Barbara Waszczak, a professor of pharmaceutical sciences in the Bouvé College of Health Sciences.

“Parkinson’s is caused by the death of dopamine neurons in a key motor area of the brain called the substantia nigra,” said Waszczak. If you want to treat PD at its roots, she added, then you have to stop the death of these neural cells. In research reported earlier this week at the Experimental Biology 2013 conference in Boston, Waszczak and graduate student Brendan Harmon proposed a treatment approach that does exactly that. What’s more, the method is simple and easy to use.

A naturally produced protein called glial cell-line-derived neurotropic factor, or GDNF, protects certain cells—including dopamine neurons—against death by activating survival and growth-promoting pathways within, according to Waszczak. In petri dishes on the lab bench, GDNF does a great job restoring function to damaged and dying dopamine neurons and preventing further loss. But getting GDNF into the actual animal brain, which is hard to access from the outside, isn’t so simple.

Crossing the so-called “blood brain barrier” has proved a difficult challenge for Parkinson’s researchers. But in previous work, Waszczak’s lab showed that GDNF could be delivered to the right location inside the brain through 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, Harmon took it a step further, by transfecting brain cells with a gene for GDNF. “We used a nanoparticle delivery system that incorporates the genetic material to make GDNF into the DNA itself,” said Harmon. “It’s like a factory, producing the protein from inside the brain.” Copernicus Therapeutics engineered the nanoparticles.

Harmon first showed that intranasal delivery of the nanoparticles increased GDNF production in the brain. Then he showed that the treatment could greatly reduce the loss of dopamine neurons in a rat with Parkinson’s disease. Now the rat’s brain can essentially make its own medicine.

Parkinson’s patients don’t begin showing symptoms until 80 to 90 percent of their dopamine cells have died, said Waszczak. At that point, GDNF would have little use. But for those recently diagnosed with PD or thought to be at a high risk for the disease, this new treatment represents a neuroprotective and neurorestorative approach. “If we can get at it in the early stages of the disease, when patients are just starting to develop symptoms, then we might be able to stop the disease from getting worse or at least delay the onset of severe symptoms,” Waszczak explained.

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