Stem cells, GDNF and Parkinson’s Disease by Clive Svendsen  Stem cells and the growth factor glial cell line derived neurotrophic factor (GDNF) have been in the news lately as potential treatments for Parkinson’s disease.   At the Waisman center there has been intense activity in both these areas of research.  Dr. Su Chun Zhang has been deriving the important dopamine neurons that are lost in Parkinson’s disease from human embryonic stem cells.  In the adjacent laboratory Dr. Clive Svendsen has been generating human neural stem cells that release GDNF.   In close collaboration they submitted a proposal to the Michael J. Fox Foundation for Parkinson’s Research (MJFF) (http://www.michaeljfox.org/) aimed at combining these two technologies.  The idea was to put GDNF secreting stem cells together with the developing dopamine neurons and see if this improved their survival and function after transplantation into animal models of Parkinson’s disease.  In a highly competitive review process the grant was recently awarded and the studies will be starting immediately.   This is the third grant that the Waisman Center has been awarded from the MJF foundation.  Both the Zhang and Svendsen labs previously applied for and were awarded grants from the first MJF foundation initiative aimed at generating lines of human stem cells for Parkinson’s disease.  Intense excitement remains around the possible use of GDNF in directly fighting the degenerative process in Parkinson’s disease.  Svendsen in collaboration with neurosurgeon Steve Gill published a 2003 report in Nature Medicine showing that GDNF could have significant positive effects when infused directly into the brain of five patients with Parkinson’s disease. A follow up study has just been accepted for publication in Annals of Neurology showing that these improvements continue over a 3 year period.  Controversy has been ripe though as a recent larger trial by AMGEN (the company that produces GDNF) apparently failed to reproduce these findings.  Furthermore some patients generated antibodies to GDNF and there is new monkey data suggesting some toxicity at very high doses from AMGEN.  However, many questions remain over the new AMGEN study, and patients definitely feel they have benefited from GDNF (http://www.gdnf4parkinsons.org/).  Furthermore, the FDA recently left the door open to continuation of GDNF therapy.  The MJF foundation organized a summit meeting on GDNF recently.  As a result of this meeting Dr. Svendsen recently received the fourth grant from the MJFF in collaboration with Dr. Hei who runs the Waisman Clinical Biomanufacturing Facility.  Together they will study the differences of GDNF made by human stem cells when compared to GDNF made by AMGEN.  This may have important implications for future clinical trials.   In related research on campus, Dr. Marina Emborg at the UW Primate Center and Dr. Svendsen recently received significant funding from another foundation (Kinetics) focused on Parkinson’s disease.  In this study, GNDF secreting human neural stem cells will be transplanted into a primate model of PD as part of essential pre clinical studies aimed at moving this technology into carefully designed clinical trials.  The Waisman link with Parkinson’s’ Disease moves from strength to strength.  Interactions with the Michael J. Fox Foundation will also be enhanced by the recent appointment of Dr. Svendsen onto their scientific advisory board.   Our aim is that in the years to come that GDNF and stem cells will start to make an impact on this devastating disease.

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