In patients with Huntington disease (HD), measurement of salivary protein huntingtin (Htt) offers considerable promise as a relevant, noninvasive disease biomarker for HD that might prove beneficial in upcoming clinical trials involving Htt-lowering strategies, according to the results of a study conducted at the University of California, San Diego, HD Clinical Research Center that were published in Scientific Reports.
The investigators sought to determine whether total Htt protein (normal plus mutant; “tHtt”) could be reliably measured in human saliva and whether salivary levels of tHtt are clinically meaningful. It has already been acknowledged that the measurement of Htt in the brains of patients with HD is not possible.
A total of 146 saliva samples were collected from patients with manifest HD, early-premanifest individuals, late-premanifest individuals, gene-negative family members, and normal controls. According to the researchers, tHtt protein could be reliably and stably detected in human saliva.
The tHtt concentrations were significantly increased in the saliva from patients with manifest HD compared with normal controls (P =.022). No significant difference was observed in salivary tHtt of normal controls compared with saliva from gene-negative family members of a person with the disease.
No gender effects were identified in salivary tHtt, nor were the levels of tHtt associated with the levels of total protein in saliva. Salivary tHtt was found to be significantly and positively linked to age, but not to age at disease onset or to CAG repeat length in the HTT gene. Notably, salivary tHtt was significantly associated with a number of clinical measures, which indicated relevance to onset of disease symptoms and/or severity of disease.
The investigators concluded that the measurement of salivary tHtt in patients with HD could be implemented into clinical research and therapeutic applications.
Corey-Bloom J, Haque AS, Park S, Nathan AS, Baker RW, Thomas EA. Salivary levels of total huntingtin are elevated in Huntington’s disease patients. Sci Rep. 2018;8(1):7371.