Elevated levels of a specific protein in the saliva of Huntington’s disease patients may be used as a biomarker to measure motor function and clinical outcomes, according to researchers.
Their study, “Salivary levels of total huntingtin are elevated in Huntington’s disease patients,” was published in the journal Scientific Reports.
The mutation responsible for Huntington’s disease is an abnormal CAG repeat expansion in the HTT gene, which leads to defects in the huntingtin (Htt) protein.
There’s a great variability in disease onset and severity and usually, the number of repeats inversely correlates with a person’s age when disease symptoms appear.
But patients with an identical CAG repeat number, especially those with 40-44 repeats, can have disease onset at ages that differ by more than 20 years.
Htt protein levels in the blood have been used with success as a biomarker for the disease. However, large volumes of blood are usually required and the results can vary. Also, drawing blood is considered an invasive technique.
Researchers tested whether saliva could be used to measure the levels of Htt protein, a strategy that has been successfully used in other neurodegenerative diseases, such as Alzheimer’s and Parkinson’s.
A total of 146 saliva samples were collected from manifest (symptomatic) Huntington’s patients; early-premanifest individuals; late-premanifest patients; gene-negative family members (patients with an affected parent, but who did not inherit the disease mutation); and normal controls.
Total levels of Htt protein — the normal plus mutated forms of the protein — were significantly increased in saliva samples from manifest Huntington’s patients compared to normal controls.
There was a tendency for increased total levels of Htt protein in saliva from early premanifest (EPM) patients when compared to normal controls, but the difference was not sufficient to reach statistical significance.
Although a correlation between total levels of salivary Htt protein and age was detected, no association was found with age of disease onset or length of CAG repeats.
Importantly, total levels of salivary Htt had a significant correlation with several clinical measures of motor function, namely the Unified Huntington’s Disease Rating Scale (UHDRS), a rating system to measure the severity of Huntington’s disease, and Total Functional Capacity (TFC), the main assessment tool of functional status in Huntington’s clinical care and research.
“Measurements of salivary tHtt [total Htt] offer significant promise as a relevant, noninvasive disease biomarker for HD, and its use could be implemented into both clinical research and therapeutic applications,” researchers wrote.