Arches. Photo by Daniel Chia
HOPES: Huntington's Outreach Project for Education, at Stanford



Because of the ability of neurotrophic factors (NTFs) to protect dying neurons, scientists believe that these proteins could one day be used to treat neurodegenerative disorders such as Huntington’s disease (HD) and Parkinson’s disease. One NTF currently being examined is neurturin, a member of the Glial cell line-derived neurotrophic factor (GDNF) family. Studies performed in living organisms ( in vivo) suggest that neurturin is not essential for survival. Mice born without neurturin are able to grow, reproduce and survive similar to mice born with neurturin. However, these in vivo studies of mice provide evidence that neurturin is essential for certain neural functions, such as controlling the sensory nerves. Additionally, neurturin has been shown to promote the survival of certain neurons in vitro, including those found in the sympathetic nervous system, the dorsal root ganglion, and the midbrain.

Does neurturin affect the progression of HD?^

Neurturin and its receptor can be found in the striatum, the region of the brain that is greatly affected by HD (Click here to see our section on the effects of HD on striatal neurons). One in vivo study compared the protective effects of neurturin and GDNF (the namesake NTF of the GDNF family) by engineering cells to serve as NTF production factories and grafting, or transplanting, these cells into mice. These mice were then given injections of chemicals intended to mimic the excitotoxic model of HD (Click here to see our section on the excitotoxic model). Neurturin was not only more effective than GDNF at rescuing a specific type of striatal neurons, but the former NTF also reduced the extent of neuronal damage caused by excitotoxic damage. Interestingly, the study found that neurturin and GDNF interacted with striatal neurons in different ways, suggesting that these factors may work together to protect these neurons. Indeed, GDNF has been found to be more effective than neurturin at protecting certain populations of striatal interneurons, nerve cells that connect afferent neurons (those that carry sensory information to the brain) and efferent neurons (those that carry nerve impulses away from the brain). Future research may look at ways of combining different NTFs to more effectively preserve damaged neurons.

Can neurturin one day be used to treat human patients with neurodegenerative diseases?^

The therapeutic application of neurturin is currently being investigated in a series of clinical trials run by the drug company Ceregene. A major challenge to the therapeutic use of neurturin and other NTFs is figuring out how to sustainably deliver these compounds into the brain. Because NTFs do not cross the blood-brain barrier, they cannot be administered orally. One proposed method has been the use of viral vectors to deliver a gene engineered to over-express neurturin into the striatum (For more information on viral vectors, click here). These genes can be thought of as neuturin factories, designed to increase the levels of neuturin produced by these cells. Once introduced, viral vectors with these genes have been shown to consistently and selectively deliver neurturin to dying neurons in cultures. Scientists at Ceregene have demonstrated that the viral vector delivery of neuturin (trade name: CERE-120) protected damaged neurons in mice and monkey models of Parkinson’s disease. Based on these results, CERE-120 for Parkinson’s disease is currently being evaluated in Phase II clinical trials. However, recent results have not been encouraging—patients treated with CERE-120 failed to show significant improvements over those who did not receive treatment. As a result, Ceregene is currently evaluating their future plans for CERE-120.

CERE-120 has also been proposed as a potential treatment for HD. The administration of CERE-120 to mouse models of HD showed evidence of both structural and functional protection of nerve cells—the mice not only showed decreased rates of neuron death, but also exhibited improved motor control. Positive results have been observed both in transgenic HD rodents, as well as rodents chemically induced to show symptoms of HD. The use of CERE-120 in humans to treat HD is currently being evaluated in pre-clinical development. Updates on the progress of CERE-120 will be added to this page as necessary.

For Further Reading^

  • Alberch, J., Pérez-Navarro, E., & Canals, J.M. (2002) Neuroprotection by neurotrophins and GDNF family members in the excitotoxic model of Huntington’s Disease. Brain Research Bulletin 57(6): 817-822.
    • This paper reviews the research on the potential of NTFs in the GDNF family to protect neurons in animal models of Huntington’s disease. Primarily written for scientists.
  • Ceregene. Pipeline. Accessed October 7, 2009.
  • Gasmi, M., Brandon, E.P., Hergoz, C.D. et al. (2007) AAV2-mediated delivery of human neurturin to the rat nigrostriatal system: Long-term efficacy and tolerability of CERE-120 for Parkinson’s disease. Neurobiology of Disease 27: 67-70.
    • This very technical article examines the effect of using a viral vector (CERE-12) to deliver neurturin to rats in order to treat Parkinson’s disease-like symptoms.
  • Heuckeroth, R., Enomoto, H., Grider, J., et al. (1999) Gene targeting reveals a critical role of neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons. Neuron 22(2): 253-263.
    • This article seeks to characterize the normal functions of neurturin by examining mice incapable of producing this NTF. Although the language is technical at times, the article is pretty easy to understand.
  • Kordower, J.H., Hergoz, C.D., Dass, Biplob, et al. (2006) Delivery of neurturin by AAV2 (CERE-120)-mediated gene transfer provides structural and functional neuroprotection and neurorestoration in MPTP-treated monkeys. Annals of neurology 60: 706-715.
    • This technical article examines the effectiveness of CERE-120 in monkey models of PD. New treatments are usually tested on monkeys before they go into clinical trials.
  • Pérez-Navarro, E., Akerud, P., Marco, S., et al. (2000) Neurturin protects striatal projection neurons but not interneurons in a rat model of Huntington’s Disease. Neuroscience 98(1): 89-96.
    • This article investigates the ability of neurturin to protect striatal neurons in rodent models of HD. The language can get very technical, but its conclusions are very clear and easy to understand.
  • Ramaswamy, S., McBride, J.L., Han, I., et al. (2008) Intrastriatal CERE-120 (AAV-Neurturin) protects striatal and cortical neurons and delays motor deficits in a transgenic mouse model of Huntington’s disease. Neurobiology of Disease 34: 40-50.
    • This article examines the effectiveness of CERE-120 in the treatment of transgenic mice with the mutated Huntington gene. The introduction is pretty accessible to all readers.
  • Ramaswamy, S., McBride, J.L., Hergoz, C.D. (2007) Neurturin gene therapy improves motor function and prevents death of striatal neurons in a 3-nitropropionic acid rat model of Huntington’s disease. Neurobiology of Disease 26: 375-384.
    • This article uses CERE-120 to treat rats chemically induced to exhibit HD-like symptoms. The writing is quite technical throughout.

-Y. Lu, 1-17-10