Original Article

Gene Therapy (2006) 13, 379–388. doi:10.1038/sj.gt.3302679; published online 15 December 2005

Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates

S Behrstock1, A Ebert1, J McHugh1, S Vosberg2, J Moore1, B Schneider1, E Capowski1, D Hei2, J Kordower3, P Aebischer4 and C N Svendsen1

  1. 1Waisman Center and Department of Anatomy, University of Wisconsin-Madison, WI, USA
  2. 2Waisman Center Clinical Biomanufacturing Facility, University of Wisconsin-Madison, WI, USA
  3. 3Rush University Medical Center, Chicago, IL, USA
  4. 4Swiss Federal Institute of Technology, Lausanne, Switzerland

Correspondence: Professor CN Svendsen, The Waisman Center and Department of Anatomy, The University of Wisconsin-Madison, 1500 Highland Avenue, Madison, WI 53705, USA. E-mail: SVENDSEN@Waisman.Wisc.Edu

Received 7 June 2005; Revised 19 September 2005; Accepted 21 September 2005; Published online 15 December 2005.



Glial cell line-derived neurotrophic factor (GDNF) has been shown to increase the survival and functioning of dopamine neurons in a variety of animal models and some recent human trials. However, delivery of any protein to the brain remains a challenge due to the blood/brain barrier. Here we show that human neural progenitor cells (hNPC) can be genetically modified to release glycosylated GDNF in vitro under an inducible promoter system. hNPC-GDNF were transplanted into the striatum of rats 10 days following a partial lesion of the dopamine system. At 2 weeks following transplantation, the cells had migrated within the striatum and were releasing physiologically relevant levels of GDNF. This was sufficient to increase host dopamine neuron survival and fiber outgrowth. At 5 weeks following grafting there was a strong trend towards functional improvement in transplanted animals and at 8 weeks the cells had migrated to fill most of the striatum and continued to release GDNF with transport to the substantia nigra. These cells could also survive and release GDNF 3 months following transplantation into the aged monkey brain. No tumors were found in any animal. hNPC can be genetically modified, and thereby represent a safe and powerful option for delivering growth factors to specific targets within the central nervous system for diseases such as Parkinson's.


GDNF, stem cell, cell therapy, neurodegeneration