CERE-120 (AAV-Neurturin) is neuroprotective in HD mouse model

Neurturin. a neurotrophic factor, protected striatal and cortical neurons in an HD mouse model.

Ceregene recently announced that their Phase II clinical trial of the neurotrophic factor neurturin gene delivered through an adeno-associated viral vector was ineffective for Parkinson's Disease patients.

The study below reports that preclinical research with this same treatment in an HD mouse model delayed the onset of motor problems and provided neuroprotection as defined by the amount of brain cell loss.  It could be that neurturin would be more effective for HD patients or it might be that the mouse research would not translate to human patients.  Preclinical and Phase I studies looked promising in PD.

Marsha L. Miller, Ph.D.
Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington's disease
Shilpa Ramaswamy, Jodi L. McBride, Ina Han, Elizabeth M. Berry-Kravis, Lili Zhou, Christopher D. Herzog
Members of the GDNF family of ligands, including neurturin (NTN), have been implicated as potential therapeutic agents for Huntington's disease (HD). The present study examined the ability of CERE-120 (AAV2-NTN) to provide structural and functional protection in the N171-82Q transgenic HD mouse model. AAV2-NTN therapy attenuated rotorod deficits in this mutant relative to control treated transgenics (p<0.01). AAV2-NTN treatment significantly reduced the number of transgenic mice that exhibited clasping behavior and partially restored their stride lengths (both p<0.05). Stereological counts of NeuN-ir neurons revealed a significant neuroprotection in the striatum of AAV2-NTN treated relative to control treated transgenics (p<0.001). Most fascinating, stereological counts of NeuN-labeled cells in layers V-VI of prefrontal cortex revealed that intrastriatal AAV2-NTN administration prevented the loss of frontal cortical NeuN-ir neurons seen in transgenic mice (p<0.01). These data indicate that gene delivery of NTN may be a viable strategy for the treatment of this incurable disease.
Neurobiology of Disease 2008 Dec 25