Parkinson’s Disease

Approximately 60,000 Americans are diagnosed with Parkinson’s disease each year and an estimated 10 million people worldwide are living with the progressively worsening, degenerative disease.

Overview

Parkinson’s disease (PD) affects neurons in a region of the brain called the substantia nigra. For reasons that remain unknown, neurons in this region begin to degenerate over time. Since substantia nigra neurons modulate muscle movement, patients suffer progressive loss of motor coordination and develop tremors, and often experience cognitive decline. Many of the affected neurons signal via the neurotransmitter dopamine; thus traditional therapy continues to rely on dopamine replacement therapy. This approach alleviates symptoms, but does not halt disease progression. Currently, there is no cure for PD.

Over the last decade researchers have realized that persistent inflammation in the brain, although not the cause of PD, may increase the rate of neuronal loss. Interestingly, epidemiological studies reveal that the risk of developing PD is less in individuals who often use of non-steroidal anti-inflammatory drugs (or NSAIDs). Stronger support for inflammation as a factor in PD comes from work in animal models of PD, which shows that drugs that inhibit pro-inflammatory responses by targeting the cytokine TNF can prevent degeneration of substantia nigra neurons. These findings have led many researchers to conclude that interventions that decrease anti-inflammation could slow neurodegeneration seen in PD.

Alessandro Sette, Ph.D., a vaccine biologist at LJI, is investigating factors that foment the immune response in PD in hopes of targeting them to slow disease progression. His group has evidence that compared to age-matched healthy controls, a greater proportion of Parkinson’s patients show activated T cell responses to a fragment derived from a protein implicated in Parkinson’s pathogenesis.

This is an exciting finding as it suggests that the immune responses activated in at least this subset of PD patients resemble those driving autoimmune diseases like multiple sclerosis. The Sette lab is further analyzing T cell responses in these patients and asking whether fragments from other proteins known to destroy neurons in PD can also generate T cell responses in patients. If so, those could be targeted in hopes of blocking excessive inflammation that accompanies and hastens loss of irreplaceable neurons.

FACULTY MEMBERS

Alessandro Sette, Dr. Biol.Sci.

From The Lab

Jan 23, 2018

Groundbreaking Parkinson’s research at La Jolla Institute funded by Michael J. Fox Foundation

Jun 21, 2017

Century-old Parkinson's question answered

Jun 30, 2017 // LJI Lab rounds

Parkinson's Disease

Jun 21, 2017 // Nature

Parkinson's is partly an autoimmune disease, study finds

Jun 16, 2016

La Jolla Institute receives research grant from The Michael J. Fox Foundation