Salivary Gland Biopsies as a Diagnostic Test for Parkinson's Disease
Rapid Response Innovation Awards, 2011
We have previously found that in autopsied patients with Parkinsonís disease the hallmark finding in the brain (Lewy body or Lewy neurite) is also found in the submandibular gland. We propose to perform both submandibular gland and minor salivary gland (in the lower lip) biopsies from 10 patients with Parkinsonís disease (PD). If the Lewy body/neurite changes are found then this would have the potential to become the first tissue-based diagnostic test for PD and would significantly increase the accuracy of the diagnosis.
Ten patients with Parkinsonís disease, age between 50 and 85, duration of PD greater than 5 years, and clearly responding to levodopa or a dopamine agonist, will be recruited into this study. They will have two outpatient procedures on the same day in the office: 1) a needle biopsy of the submandibular gland† and 2) a small incision in the lower lip will be made for removal of a minor salivary gland. These procedures just require some local numbing medication. The tissue will then be treated with special stains and will be examined under a microscope to see if there are Lewy bodies or Lewy neurites present. These are characteristic of Parkinsonís disease.
Relevance to Diagnosis/Treatment of Parkinsonís Disease:††
The idea is that salivary gland biopsies would be the first tissue-based diagnostic test for PD. This would allow for a significant increase in the clinical diagnostic accuracy of PD, hopefully at even earlier stages. This would result in more accurate subject selection for clinical trials and in more advanced cases may help in selection for the appropriate patients having neurosurgical procedures, such as deep brain stimulation surgery, and experimental treatments such as transplants.
We expect to determine whether salivary gland biopsies have the potential to diagnose PD. This is a small pilot study of only 10 PD patients so that the information will be preliminary and would form the basis of a much larger project investigating salivary gland biopsies in both advanced as well as earlier stages of PD.
Saliva gland biopsies were performed and reviewed for evidence of alpha-synuclein, the protein that is found in Lewy bodies in the brains of patients with Parkinsonís disease. Fifteen PD patients who had a mean age of 68.7 years and mean disease duration of 11.8 years had the lower lip and the submandibular gland biopsied. Only one of the 15 lower lip biopsies had the alpha-synuclein protein present. Three of the needle biopsies of the submandibular gland did not have gland tissue to study. Of the 12 with gland tissue present, 9/12 (75%) had the alpha-synuclein protein present. The biopsies were well tolerated with some bruising and swelling being the main side effect. This study demonstrates that needle biopsies of the submandibular gland may be a diagnostic test for patients with long-standing PD.
Consultant and Professor, Department of Neurology at Mayo Clinic College of Medicine