AT ANA 2017

SAN DIEGO (FRONTLINE MEDICAL NEWS) – Huntingtin protein – the key biomarker for Huntington’s disease – can be detected in saliva, which might prove to be an easy and inexpensive way to diagnose and monitor Huntington’s, and perhaps even predict clinical onset, according to investigators at the University of California, San Diego.

In a study of 178 subjects, they found that salivary total huntingtin protein (Htt) was significantly increased in saliva from individuals with Huntington’s disease (HD), compared with controls without HD (mean, 0.775 ng/mL vs. 0.359 ng/mL; P = .0012). Levels remained consistent throughout the day and from day to day, and were not affected by age or sex.

Salivary Htt level also correlated with motor scores on the Unified Huntington’s Disease Rating Scale (Spearman’s rho = 0.264, P = .049) and total functional capacity scores (Spearman’s rho = –0.283; P = .032).

Meanwhile, salivary mutant Htt levels were higher in gene-positive, premanifest HD subjects than in normal controls (P less than .05). Salivary C-reactive protein level was also significantly elevated in premanifest HD subjects (9,548 pg/mL vs. 3,399 pg/mL, P = .025), indicating a pathologic inflammatory or metabolic state. When considered together, the two measurements might herald the onset of symptoms.

There’s an acute need for a convenient, inexpensive HD biomarker. Htt isn’t often measured in clinical practice, and when it is, it’s assessed from blood or cerebrospinal fluid. With salivary Htt, “you don’t need any specialized personnel, [and samples] are easy to obtain and process. They keep well and are very stable. We don’t have to rush to get them somewhere,” said lead investigator Jody Corey-Bloom, MD, PhD , professor emeritus of neurosciences at the university.

“We are really excited about the potential of salivary Htt. We think this is going to be an easy way to follow patients,” she said at the annual meeting of the American Neurological Association.

The next step is to see how salivary Htt correlates with cerebrospinal fluid and blood levels. The team will also investigate it as a diagnostic tool; perhaps there’s a cut point that diagnoses HD. “It’s an intriguing idea,” Dr. Corey-Bloom said.

Perhaps the greatest potential is for predicting disease onset so treatments can be started before symptoms emerge. There’s nothing on the market yet that can delay or prevent progression, but trials are in the works for therapeutics that lower levels of mutant Htt in the brain. “If we can use something simple like salivary Htt [to start preemptive treatment] that would be phenomenal. That’s the hope,” she said.

Subjects refrained from smoking, eating, drinking, and brushing their teeth for at least an hour before saliva samples were taken. Testing was done by Western blot and enzyme-linked immunosorbent assay.

The work was funded by the university. Dr. Corey-Bloom said she had no relevant disclosures.