A noninvasive avenue for Parkinson's disease gene therapy

April 21, 2013, Federation of American Societies for Experimental Biology

Researchers at Northeastern University in Boston have developed a gene therapy approach that may one day stop Parkinson's disease (PD) in it tracks, preventing disease progression and reversing its symptoms. The novelty of the approach lies in the nasal route of administration and nanoparticles containing a gene capable of rescuing dying neurons in the brain. Parkinson's is a devastating neurodegenerative disorder caused by the death of dopamine neurons in a key motor area of the brain, the substantia nigra (SN). Loss of these neurons leads to the characteristic tremor and slowed movements of PD, which get increasingly worse with time. Currently, more than 1% of the population over age 60 has PD and approximately 60,000 Americans are newly diagnosed every year. The available drugs on the market for PD mimic or replace the lost dopamine but do not get to the heart of the problem, which is the progressive loss of the dopamine neurons.

The focus of Dr. Barbara Waszczak's lab at Northeastern University in Boston is to find a way to harvest the potential of glial cell line-derived neurotrophic factor (GDNF) as a treatment for PD. GDNF is a protein known to nourish dopamine neurons by activating survival and growth-promoting pathways inside the cells. Not surprisingly, GDNF is able to protect dopamine neurons from injury and restore the function of damaged and dying neurons in many animal models of PD. However, the action of GDNF is limited by its inability to cross the blood-brain barrier (BBB), thus requiring direct surgical injection into the brain. To circumvent this problem, Waszczak's lab is investigating intranasal delivery as a way to bypass the BBB. Their previous work showed that intranasal delivery of GDNF protects dopamine neurons from damage by the , 6-hydroxydopamine (6-OHDA), a standard of PD.

Taking this work a step further, Brendan Harmon, working in Waszczak's lab, has adapted the intranasal approach so that cells in the brain can continuously produce GDNF. His work utilized , developed by Copernicus Therapeutics, Inc., which are able to transfect brain cells with an expression plasmid carrying the gene for GDNF (pGDNF). When given intranasally to rats, these pGDNF nanoparticles increase GDNF production throughout the brain for long periods, avoiding the need for frequent re-dosing. Now, in new research presented on April 20 at 12:30 pm during Experimental Biology 2013 in Boston, MA, Harmon reports that intranasal administration of Copernicus' pGDNF nanoparticles results in GDNF expression sufficient to protect SN dopamine neurons in the 6-OHDA model of PD.

Waszczak and Harmon believe that intranasal delivery of Copernicus' nanoparticles may provide an effective and non-invasive means of GDNF gene therapy for PD, and an avenue for transporting other gene therapy vectors to the brain. This work, which was funded in part by the Michael J. Fox Foundation for Parkinson's Research and Northeastern University, has the potential to greatly expand treatment options for PD and many other central nervous system disorders.

Explore further: Innovative new strategy to treat Parkinson's disease

Related Stories

Innovative new strategy to treat Parkinson's disease

December 19, 2011
Stabilizing the cell's power-generating center protects against Parkinson's disease (PD) in a rat model, according to a report published online this week in the Journal of Experimental Medicine.

Reprogramming brain cells important first step for new Parkinson's therapy, study finds

December 13, 2011
(Medical Xpress) -- In efforts to find new treatments for Parkinson’s Disease (PD), researchers from the Perelman School of Medicine at the University of Pennsylvania have directly reprogrammed astrocytes, the most plentiful ...

Recommended for you

Parkinson's disease 'jerking' side effect detected by algorithm

January 8, 2018
A mathematical algorithm that can reliably detect dyskinesia, the side effect from Parkinson's treatment that causes involuntary jerking movements and muscle spasms, could hold the key to improving treatment and for patients ...

New brainstem changes identified in Parkinson's disease

January 4, 2018
A pioneering study has found that patients with Parkinson's disease have more errors in the mitochondrial DNA within the brainstem, leading to increased cell death in that area.

Caffeine level in blood may help diagnose people with Parkinson's disease

January 3, 2018
Testing the level of caffeine in the blood may provide a simple way to aid the diagnosis of Parkinson's disease, according to a study published in the January 3, 2018, online issue of Neurology, the medical journal of the ...

Researchers shed light on why exercise slows progression of Parkinson's disease

December 22, 2017
While vigorous exercise on a treadmill has been shown to slow the progression of Parkinson's disease in patients, the molecular reasons behind it have remained a mystery.

Robotic device improves balance and gait in Parkinson's disease patients

December 19, 2017
Some 50,000 people in the U.S. are diagnosed with Parkinson's disease (PD) every year. The American Institute of Neurology estimates there are one million people affected with this neurodegenerative disorder, with 60 years ...

New findings point to potential therapy for Parkinson's Disease

December 19, 2017
A new study, published in Proceedings of the National Academy of Sciences (PNAS), sheds light on a mechanism underlying Parkinson's disease and suggests that Tacrolimus—an existing drug that targets the toxic protein interaction ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.