The news out of Northeastern University’s Dr. Barbara Waszczak’s lab is exciting but it’s a single high point in a larger narrative. First, here’s the high point described in the Apr. 24, 2013 news item on Azonano,
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.
The Apr. 21, 2013 news release on EurekAlert, which originated the news item, provides some information about Parkinson’s disease,
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.
Here’s how the disease got its name, from the Wikipedia essay: Parkinson’s disease (Note: Links have been removed),
The disease is named after the English doctor James Parkinson, who published the first detailed description in An Essay on the Shaking Palsy in 1817. Several major organizations promote research and improvement of quality of life of those with the disease and their families. Public awareness campaigns include Parkinson’s disease day (on the birthday of James Parkinson, April 11) and the use of a red tulip as the symbol of the disease. People with parkinsonism who have increased the public’s awareness include Michael J. Fox and Muhammad Ali.
Now for some information about the background work leading up to this new, exciting, high point (from the news release on EurekAlert),
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 neurotoxin, 6-hydroxydopamine (6-OHDA), a standard rat model of PD.
According to the Michael J. Fox Foundation, this research work dates from 2007 (at least), from the Intranasal Delivery of GDNF for Parkinson’s Disease: Next Steps grant page,
The results of this Drug Delivery 2008 project confirm and extend the conclusions reached under a previous 2007 Rapid Response Innovation Award. The research team has demonstrated that intranasal administration of GDNF has neuroprotective efficacy in a preclinical model of Parkinson’s disease, that the protein gets into the brain and reaches target structures (the striatum and substantia nigra) within an hour of nasal administration, and that the nasal route causes no apparent toxicity in the nose. Longer term efficacy and toxicology studies will be necessary in other relevant preclinical models before testing can be initiated in humans.
The results of this work strongly supports pursuit of intranasal administration as a promising approach for harvesting the therapeutic potential of GDNF. Such an approach could ultimately provide an effective, non-invasive means of delivering GDNF to the brain for the treatment of Parkinson’s disease.
Here’s the 2013 innovation on intranasal delivery of GDNF therapy (from the news release on EurekAlert),
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 nanoparticles, 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.
For the curious, there’s more about Copernicus Therapeutics at the company website.
Congratulations to Harmon and Waszczak! I imagine the next step will be human clinical trials.