Abstract
Huntington’s disease (HD) is a neurodegenerative disorder caused by the huntingtin (HTT) gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT) exists in the liver and causes urea cycle deficiency. A low protein diet (17%) restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories) than in mice (~22%). We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein) for 5 days, followed by a high protein diet (HPD, 26.3% protein) for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington’s Disease Rating Scale (UHDRS). The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (p = 0.0378) in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.
Highlights
Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by the expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene
We have reported the beneficial effects of two different low protein diets (17% of total calories) in two HD model mice [13], it is unclear whether this finding can be translated to humans with HD because the normal human protein content is lower than that of mice (15% and 22% of total calories, respectively) [13,24]
Given that the standard protein content is lower in humans than in mice (15% and 22% of total calories, respectively) and that a well-monitored HPD can be beneficial at least in normal subjects [33], we increased the dietary protein content from 13.7% to 26.3% of total calories through the HPD and monitored the effects on urea cycle function in HD patients
Summary
Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by the expansion of CAG repeats in exon 1 of the huntingtin (HTT) gene. The clinical features of HD include uncontrollable motor movements, psychiatric abnormalities, dementia, and weight loss. This devastating disease preferentially affects the cerebral cortex and striatum in the central nervous. Dietary Protein and Huntington's Disease system [1]. Abnormalities in the peripheral tissues, including the cardiovascular system, skeletal muscles, blood cells, and cochlea, have been reported [2,3,4,5,6]. Whether dysregulated peripheral functions can serve as reliable biomarkers of the progression of HD has been discussed [7]
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