Two years ago French researchers made medical history by demonstrating that CNTF could reverse HD progression a primate model of HD.(ref) CNTF does not cross the blood brain barrier so delivery is a problem. Now the same researchers, in just two years, have taken another big step by demonstrating that a virus can effectively deliver CNTF.

Posted to HDLighthouse: 02-Jun-2002 HDL Update: Gene Therapy Success

Massive Protection The study, published in the Journal of Neuroscience, June 1, 2002, concludes, "Overall, adenovirus-mediated CNTF gene transfer appears to be a potentially useful delivery system for widespread, long-term neuroprotection in HD patients."

Ciliary neurotrophic factor (CNTF) is a potent protective factor for striatal neurons in animal models of Huntington's disease (HD).

Clinical application of this potential therapeutic still requires the design and optimization of delivery systems. In the case of HD, spatial spread in the vast volume occupied by the striatum and long-term delivery of the factor are particular challenges for these systems.

We explored the potential of adenovirus-mediated gene transfer to fulfill these requirements by studying the functional and anatomical effects of single-site striatal delivery of CNTF recombinant vectors in a rat model of HD.

In an initial series of experiments, unilateral injections of CNTF adenovirus were performed in rats 10, 30, or 90 d before a 5 d neurotoxic treatment with systemic 3-nitropropionic acid (3NP).

Preservation of striatal neurons was observed at all time points, demonstrating temporally extended neuroprotective effects of the CNTF adenovirus. In a second series of experiments, bilateral injections of CNTF adenovirus were performed in the medial aspect of the striatum 10 d before starting 3NP intoxication. Despite placement of the CNTF-producing vector outside the lateral striatal area susceptible to lesion, massive protection of corticostriatopallidal circuits was observed, associated with significant behavioral benefits.

Source: Adapted from J Neurosci 2002 Jun 1;22(11):4478-4486 Mittoux V, et al.

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