Scientists at La Jolla Institute for Immunology (LJI) have found that people with Parkinson’s disease have a clear “genetic signature” of the disease in their memory T cells, said the study published recently in the journal npj Parkinson’s Disease.
The scientists hope that targeting these genes may open the door to new Parkinson’s treatments and diagnostics.
Parkinson’s disease (PD) is a neurodegenerative disorder that affects predominately dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra. Parkinson’s disease is a progressive nervous system disorder that affects movement.
LJI Research Assistant Professor Cecilia Lindestam Arlehamn, Ph.D. says:
Parkinson’s disease is not usually seen as an autoimmune disease, But all of our work points toward T cells having a role in the disease. Identifying these genes may allow doctors to quickly determine which patients have autoimmune T cells and provide a much-needed early diagnostic.
LJI Professor Alessandro Sette, Dr.Biol.Sci., who led the work with Lindestam Arlehamn adds:
Now that we can see what these T cells are doing, we think intervening with antibody therapies could have an impact on the disease progression, especially early on.
Parkinson’s progresses as dopamine-producing neurons in the brain die. Unfortunately, scientists have been unable to pinpoint what causes this cell death—though they do have a clue: The doomed neurons contain clumps of a damaged protein called alpha-synuclein.
LJI research suggests these clumps may be the kiss of death for dopamine-producing neurons. Sette and Lindestam Arlehamn recently showed that people with Parkinson’s have T cells that target alpha-synuclein early on in Parkinson’s disease.
Self-reactive T cells can damage the body’s own cells, including neurons. In fact, self-reactive T cells are the culprits behind many autoimmune diseases.
The new study may offer a way to stop these T cells in their tracks. The LJI team found that people with Parkinson’s disease have memory T cells with a very specific gene signature. Genes associated with targeting alpha-synuclein may very well be causing ongoing inflammation in cases of Parkinson’s.
One important gene expressed in these T cells is LRRK2. This gene is associated with the genetic, or familial, type of Parkinson’s disease. Neurons in many people with Parkinson’s express LRRK2, but the new study is the first to show this gene expressed in T cells.
But many of the genes expressed in these T cells were completely unexpected and not previously linked to Parkinson’s disease. “This finding suggests we found novel targets for potential therapeutics,” says Sette.
The scientists found these genes expressed in blood samples collected at LJI’s John and Susan Major Center for Clinical Investigation and by study collaborators at UC San Diego, Columbia University Irving Medical Center, and the University of Alabama at Birmingham.
Going forward, Lindestam Arlehamn and her collaborators plan to study post-mortem brain samples. This work will confirm whether the same self-reactive T cells found in blood also target neurons in people with Parkinson’s. The team also wants to look for other targets, called antigens, that might be recognized by T cells in individuals with Parkinson’s disease.
To translate this work to new therapies, it will be important for scientists to study how they can activate or inhibit different genes at different stages of Parkinson’s progression.
