Review: Neuroprotection for Huntington’s Disease: Ready, Set, Slow

The paper reviewed here is ‘Neuroprotection For Huntington’s Disease: Ready, Set, Slow’ by Hersch and Rosas (2008) and freely available here. As the title suggests, this paper outlines neuroprotective strategies in Huntington’s Disease. In the introduction the authors define neuroprotection thus:

Neuroprotection can be defined quite literally as the preservation of neuronal structure, function and viability, or more generically as the slowing or prevention of neurodegeneration

The authors summarise some of the demographics and other information about Huntington’s Disease in the introduction placing the theme of neuroprotection in context. In the section ‘neurodegeneration’, the authors develop the theme that neurodegeneration occurs not only in the striatum but also in the cortex and that both are important contributors to the presentation in Huntington’s Disease. They also provide supporting evidence. In the section on neuroprotection in premanifest HD, the authors look at ‘phenoconversion’ (the conversion from prodromal Huntington’s Disease to manifest Huntington’s Disease), the PHAROS and PREDICT-HD studies and the difficulties of conducting clinical trials while avoiding genetic testing in prodromal Huntington’s Disease. In ‘Neuroprotection in Manifest HD’ the authors look at the many changes that occur in manifest Huntington’s Disease including a reduction in total functioning capacity (TFC). In ‘Measurement of Neuroprotection and Treatment Approval’, the difficulties in establishing useful outcome measures in trials of premanifest HD are discussed and they show that this is a particularly challenging area with a lack of useful biomarkers as well as a need to use primary outcome measures such as TFC which may not be particularly sensitive at this stage in the disease. They note the possible utility of a futility study which involves divergence on outcomes such as TFC from a predetermined threshold which is assumed to have clinical significance on the basis of statistically significant findings in prior studies. They also provide an indication of the sample sizes and follow-up periods that are required for the studies that are needed for FDA approval. The authors then look at the place of murine models although noting the significant limitations of such studies. In the next section, the authors consider the molecular target candidates (summarised in Table 1) before finishing with a section on candidate therapies although accepting that it is not exhaustive.

This was a useful review of neuroprotection in Huntington’s Disease. As with many reviews however there is no methodology section describing how the studies were selected although from my experience this approach has been frequently adopted in reviews. Perhaps this is because the issue of reproducibility isn’t as important with review papers because they represent in some part an interpretation of a field. The theme of neuroprotection I suspect will become increasingly important, not just in Huntington’s Disease but in other forms of dementia and will be interesting to see how this field develops.

STT 3 (My reasoning is as follows. Some of the treatments described here are currently in trials. If the trials are successful this may lead to approval which in turn depending on policy could then be used in treatment).

Steps To Treatment (STT)

STT = Steps To Treatment. An estimate of the number of steps between the results and translation into treatment. This is an opinion.

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The comments made here represent the opinions of the author and do not represent the profession or any body/organisation. The comments made here are not meant as a source of medical advice and those seeking medical advice are advised to consult with their own doctor. The author is not responsible for the contents of any external sites that are linked to in this blog

4 comments

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