New Approach for GDNF as Parkinson’s Therapy

For two decades, the Parkinson’s disease (PD) community has followed the development of glial cell line-derived neurotrophic factor (GDNF) as a potential treatment for the disease. GDNF is a naturally occurring human protein that nourishes and promotes growth of dopamine neurons, the brain cells damaged and lost in PD. Over the years, although studies in animals have showed promise, clinical trials in people with PD have mostly proven disappointing.

One hurdle in using GDNF as a therapy is ensuring that it gets to the brain, and to the neurons weakened by PD. That’s because the “blood-brain barrier” protects the brain and prevents many substances — including medications injected or taken orally — from reaching it.

Researchers at the University of North Carolina at Chapel Hill have devised a new way to get past this difficulty. In research published last year in PLOS One, they found a way to harness white blood cells, which can cross the blood-brain barrier, to deliver GDNF to neurons damaged by PD. In September 2015, the research got a vote of confidence — and a boost toward commercialization — with new technology-development funding.

Led by Elena V. Batrakova, Ph.D., the scientists carried out their studies in laboratory mice developed to have PD symptoms after injection of a toxin. In the laboratory, they took mouse white blood cells, known as macrophages, and genetically modified these cells so they had the ability to produce GDNF. The reprogrammed cells also could deliver their own repair materials to damaged neurons, to enable the sick cells to heal themselves. The macrophages were then injected into the parkinsonian mice.


  • In the mice given the engineered macrophages, PD movement symptoms improved.
  • The macrophages, which are immune system cells, honed in on the damaged dopamine neurons.
  • Mice injected with the GDNF-producing macrophages also showed less brain inflammation and the loss of fewer neurons.
  • The macrophages released something called exosomes, which contained GDNF, attached themselves to the damaged neurons and then delivered GDNF.

What Does It Mean?

Researchers and people with PD continue to be hopeful that GDNF can be developed as a potential PD therapy. By using white blood cells called macrophages, the new technique overcomes two important obstacles: first, it successfully carried GDNF across the blood-brain barrier; and, second, because the macrophages are harvested from the mouse’s own body, the treatment was “accepted” by the body — the cells were not seen as foreign invaders nor were they attacked by the immune system.

Much work remains to be done before this technique for GDNF treatment could come into practical use. One major limitation of the mouse model is that injection of the toxin induces inflammation which in turn attracts macrophages. The role of macrophages in PD is not well established. However, if shown to be successful in additional pre-clinical studies, and in clinical trials with people, the hope is that this approach to a GDNF therapy could ultimately slow disease progression in people living with PD and potentially even help people who are already experiencing significant disability from PD. This technique might also be more broadly useful in delivering therapies to the brain in people with different neurological conditions.


Zhao, Y., Haney, M. J., Gupta, R., Bohnsack, J. P., He, Z., Kabanov, A. V., & Batrakova, E. V. (2014). GDNF-transfected macrophages produce potent neuroprotective effects in Parkinson's disease mouse model. PloS One, 9(9), e106867.

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