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Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.

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The authors report the inter-rater reliability and factor structure of the Short Problem Behaviors Assessment (PBA-s), a semistructured interview to measure severity and frequency of behavioral problems in Huntington's disease. Video recordings of 410 PBA-s interviews were rescored by an independent rater, and Cohen's kappa calculated to assess inter-rater reliability. The mean kappa was 0.74 for severity and 0.76 for frequency scores, whereas weighted kappa (allowing scores to differ by 1 point) was 0.94 for severity and 0.92 for frequency scores. The results of factor analysis were consistent with previous studies using other measures. The authors conclude that the PBA-s is a reliable measure.