Girija and I had a lengthy conversation with Dr. Barbara Waszczak last week and she updated us on the current status of her fascinating research for treating Parkinson's disease using a non-invasive, gene therapy via intranasal administration of GDNF. Barbara explained how her intranasal gene therapy worked and gave us details on the differences in her approach and the more widely known AAV2-GDNF. We also spent time discussing her next steps in required pre-clinical research before a submission of an IND to the FDA to begin human studies.

There are several differences between Dr. Waszczak's approach to GDNF therapy and that which is currently taking place using viral vectors encoding GDNF, known as AAV2-GDNF. The most obvious difference is the method of administration. GDNF is a protein that activates survival and growth-promoting pathways, protects dopamine neurons from injury, and restores their function. However, GDNF not cross the blood-brain barrier (BBB), so its use would require surgical injection into the brain. Barbara is investigating pGDNF encoded with DNA nanoparticles (NPs) which by-pass the BBB and allow for the brain to continuously produce its own GDNF. AAV vector research requires GDNF to be surgically implanted into the exact area needed in the substantia nigra and hope that the protein uptakes to the still living neurons. Success would still likely require multiple lifetime surgeries to maintain the GDNF production. Alternatively, administration of intranasal pGDNF allows for uptake throughout the brain and causes the cells to continuously produce their own GDNF over a long time period. Essentially, the viral vector approach surgically inserts an encoded GDNF protein. The intranasal approach inserts an encoded GDNF gene which allows cells that line blood vessels throughout the brain to begin to produce their own renewable source of GDNF.

Please keep in mind that all of her research has been on rodents. That being said, the results of those studies have been great and offer some excitement as she moves forward.
One week after intranasal administration, GDNF levels were significantly increased throughout the brain. The transfected cells were largely adjacent to capillaries, suggesting they may be pericytes. Most importantly, intranasal GDNF NPs provided significant neuroprotection of dopamine neurons in a standard rat model of PD.

I have clearly simplified matters in this brief summary. If anyone is interested, Barbara has given us a copy of a poster-board for a conference in which she will be presenting her latest, not yet released, research results. I would be happy to send this out if you're interested.

So, where do things stand today? One more rodent study is needed for dosing purposes. Then a primate study is probably required, before she can submit the IND. What we need to do now, as a community, is to make sure she gets the funding required to move forward. Girija and I have offered to assist in getting the PD community involved. How much does she need? All of $100,000. If you believe in advancing this research, we need to get the normal early research funders (i.e. MJFF, PDF, NPF, NIH, etc.) to cut a check. MJFF has funded her previous research, so I am hoping that this will go through their funding committee quickly and be approved again. However, my general point is that many people on this site, and others, complain about how slow the research process is. We complain about big pharma. We want more say in the research process. This is our time to step up. All you have to do is tell your local support groups to support this research. Contact the larger organizations (e.g. MJFF) and tell them we want our donations to get this study started immediately. Basically, it's time to act, if you want to see intranasal GDNF research move forward. Understand, no one else in the world can conduct this research. Northeastern and their corporate partner, Copernicus Therapeutics, own the patent rights to the drug. I can't imagine how it could be difficult to fund $100,000. Finally, anyone on this board that would like to assist me and Girija are more than welcome.

If we are successful getting this done, we can find more relevant research and help move it along. It's up to us PWP to take more control by advising, assisting, and twisting arms where necessary.