Tissue biopsy for identifying early Parkinson's

Aug. 30, 2017

Mayo Clinic researchers and colleagues have found that submandibular gland needle biopsies can identify Lewy type alpha-synucleinopathy in people with Parkinson's disease of less than five years' duration. The finding has implications for research enrollment criteria: The accuracy of clinical diagnosis of early Parkinson's disease may be as low as 50 percent, and a peripheral tissue biopsy could confirm diagnosis for patients enrolling in clinical trials.

"A peripheral tissue diagnostic test for early Parkinson's, similar to what we have for cancer, would be extremely valuable for trials looking at neuroprotective therapies," says Charles H. Adler, M.D., Ph.D., a consultant in Neurology at Mayo Clinic in Phoenix/Scottsdale, Arizona. "A definitive diagnosis before study enrollment avoids exposing patients who do not have Parkinson's unnecessarily to invasive treatments, and powers the accuracy of the trial. Many potential therapies for early Parkinson's have failed in human trials. One reason for that might be that some people enrolled in the studies don't actually have Parkinson's disease."

Published in the February 2016 issue of Movement Disorders, the peripheral synucleinopathy study was cited by the journal as its 2016 Best Research Article. The study was performed by the Arizona Parkinson's Disease Consortium, whose principal members are Mayo Clinic's campus in Arizona and Banner Sun Health Research Institute. It didn't address the issue of patients who don't yet have signs of Parkinson's disease on examination but who might go on to develop the condition.

Potential gold standard

Needle biopsy of the submandibular gland Needle biopsy of the submandibular gland

Photograph shows a needle biopsy of the submandibular gland. Photo reprinted with permission from Neurology. 2014;82:859.

In the study, submandibular gland needle biopsies were performed on 25 patients with early Parkinson's disease (mean disease duration of 2.6 years) and 10 control participants. Six participants with Parkinson's disease and one control participant had inadequate glandular tissue. Tissue staining for phosphorylated alpha-synuclein was positive in 14 of 19 participants with Parkinson's disease (74 percent) and 2 of 9 (22 percent) of control participants.

"The false-positives might be true false-positives, or they might represent prodromal Parkinson's disease," Dr. Adler says.

The tissue biopsy isn't intended for current routine clinical use at this time. In the absence of definitive clinical diagnosis, treatment is routine for patients with suspected early Parkinson's disease because the oral medications generally don't have permanent side effects.

In addition to facilitating clinical trials, the biopsy test may benefit genetic and epidemiologic research of Parkinson's disease. "By providing definitive diagnosis, the biopsy test could eventually serve as a gold standard for biomarker studies, short of autopsy confirmation," Dr. Adler says.

Future directions

The researchers plan to investigate whether a tissue biopsy test might aid diagnosis of prodromal Parkinson's disease — potentially in patients with nonmotor conditions, such as anosmia or rapid eye movement sleep behavior disorder, that often predate Parkinson's disease. Mayo Clinic's campus in Arizona is also participating in the Systemic Synuclein Sampling Study (S4), funded by the Michael J. Fox Foundation. S4 is comparing biopsies of submandibular gland, colon and skin tissue, as well as cerebrospinal fluid, blood and saliva, to identify biomarkers for Parkinson's disease.

"Mayo Clinic is committed to this type of translational research," Dr. Adler says. "There is synergy between our neurologists and our otorhinolaryngology colleagues who perform the biopsies. Although the submandibular gland biopsy test is primarily a research tool now, we're working to eventually bring it to the clinic."

For more information

Adler CH, et al. Peripheral synucleinopathy in early Parkinson's disease: Submandibular gland needle biopsy findings. Movement Disorders. 2016;31:250.