New gene therapy to stop Parkinson's disease in its tracks

Scientists have developed a new gene therapy approach that may one day prevent progression of Parkinson's disease (PD) and reverse 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.
The available drugs 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.

Researchers at Barbara Waszczak's lab at Northeastern University in Boston are trying 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.
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.
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 utilised 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.

In new research presented at Experimental Biology 2013 conference in Boston, Harmon reported 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.