By Lauretta Ihonor, medwireNews reporter
Measuring blood levels of mutant huntingtin (mHTT) protein may provide an alternative approach of determining the onset of Huntington's disease (HD) in known carriers, researchers report.
This strategy may also facilitate monitoring of HD progression because immune cell production of mHTT appears to increase as HD progresses, explain Sarah Tabrizi (University College London Institute of Neurology, UK) and team.
They found that mean leukocyte mHTT levels obtained from blood samples were significantly lower in eight HD gene carriers yet to manifest HD than in 18 manifest HD patients.
Premanifest HD patients had lower mHTT levels than did 10 early-stage HD patients. However, mHTT levels did not differ significantly between early-stage patients and eight moderate-stage HD patients.
In contrast to the mHTT variations seen in blood samples, cheek swab samples revealed no noticeable differences in the mean mHTT levels of the three HD patient groups.
When mHTT production by different leukocytes types was assessed, mean mHTT levels in monocytes, T cells, and B cells were found to be significantly higher among HD patients than in 12 HD-free controls.
These levels were also higher among manifest HD patients than in premanifest patients.
Writing in the Journal of Clinical Investigation, Tabrizi and colleagues say that mHTT offers a potential therapeutic target in HD patients and detection of the protein using blood sampling may assist the development of effective HD therapies.
However, they highlight that "further research will [be needed to] determine whether the techniques described here can be used to monitor mHTT-lowering therapies that may be expected to elicit systemic effects."
Additional observations concerning the link between mHTT and pathologic changes in the brain were also made in the group.
When magnetic resonance imaging (results were analyzed alongside mHTT levels, Tabrizi and team noted that monocyte and T-cell mHTT levels significantly correlated with caudate atrophy rates in patients with HD.
The researchers conclude that quantification of mHTT in peripheral leukocytes has "significant promise as a noninvasive disease biomarker."
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