GDNF - An Alternative Method of Delivery?

Glial cell derived neurotrophic factor (GDNF) has had a controversial development history to date (see previous article). Some investigators believe that the growth factor offers the best hope yet of a treatment to slow or prartially reverse Parkinson's disease. Others take a less optimistic view and cite negative results from the first sham surgery controlled studies in patients using continuous infusions of GDNF. One area where most experts seem to agree however is that the early studies did not achieve optimal distribution of the growth factor in the target areas of the brain.

Emborg and colleagues working with a team at the Wisconsin National Primate Research Center, have explored a novel method of delivering GDNF for the potential treatment of Parkinson's disease. Instead of infusing the growth factor into the brain via a catheter they genetically engineered human neural progenitor cells (hNPCs) in the laboratory creating cells which secreted GDNF. They then transplanted the engineered cells into the nigral and striatal areas of the brains of three monkeys which had been exposed to a chemical known to produced Parkinson's disease (MPTP). The animals were treated with immunosuppressive drugs to prevent rejection of the human cells. Initial results of this pilot study appear promising. Findings included the following:

1. hNPCs survived and produced GDNF in all animals 3 months postsurgery.


2. hNPCs remained in the areas of injection


3. A "halo" of GDNF expression was observed diffusing from the center of the graft out into the surrounding area.


4. An observed increased TH- and VMAT2-positive fibers in areas of GDNF delivery in two of the three animals.


5. The two animals with TH- and VMAT2-positive fibers also showed reductions in their Clinical Rating Score for Parkinson's disease.


6. The treatment appeared well tolerated.

The authors conclude that hNPCs releasing GDNF may be a possible alternative for intracerebral trophic factor delivery in Parkinson's disease. Click here to read the full abstract.


Reference:
Emborg, M.E., et al., GDNF-secreting human neural progenitor cells increase tyrosine hydroxylase and VMAT2 expression in MPTP-treated cynomolgus monkeys. Cell Transplant, 2008. 17(4): p. 383-95.