Cerebellar Degeneration in Essential Tremor: Testing the Hypothesis

IETF Funded Research

Principal Investigator:
Holly Shill, MD, FAAN, Barrow Neurological Institute, Phoenix, AZ

Co-Investigator:
Malvindar Singh-Bains, PhD, Centre for Brain Research, University of Auckland, New Zealand

Consultant:
Thomas G. Beach, MD, PhD, Banner Sun Health Research Institute, Sun City, AZ

PROJECT SUMMARY

A significant barrier in essential tremor (ET) research and development of therapeutics has been the lack of good laboratory models to study ET. This is largely because there are no well-defined genetic changes nor clear changes seen within the brain itself which could be used to model ET in the lab. For the past 15 years, there have been a number of research publications exploring the neuropathology of ET. Neuropathology means examining changes that are seen in the number of brain cells and their ability to maintain connections, most often studied at the microscopic level. Due to the progressive nature of ET combined with findings of unsteadiness and incoordination in advancing ET, the cerebellum has been a logical place to look for evidence of neurodegeneration as this is the area of the brain responsible for these symptoms. Cerebellar involvement in ET is supported by human studies of the metabolism and electrical activity in the brain with both types of studies showing overactivity of the cerebellum. Several research groups have looked at counting of cerebellar Purkinje cells and other changes in the cerebellum with conflicting results. There is a need for additional studies to clarify cerebellar pathological findings in ET in order to support or refute the hypothesis that ET may be a neurodegenerative disorder of the cerebellum. This new study funded by the IETF will use enhanced methods to study findings in the human cerebellum. If the findings can be confirmed, it will open the potential to develop better models of ET as well as potential targets for treatment.

The goal of this project is to determine whether essential tremor is a neurodegenerative disease affecting the cerebellum.