Scientists have found that a type of immune cells of people with Parkinson's disease have a very specific gene signature, a finding that may open the door to new treatments and diagnostics for the debilitating condition.Researchers at La Jolla Institute for Immunology (LJI) in California found that people with Parkinson's disease have a clear "genetic signature" of the disease in their memory T cells. These genes appear responsible for targeting alpha-synuclein and potentially causing ongoing inflammation in cases of Parkinson's.The new study, published in the journal npj Parkinson's Disease, offers a way to stop these T cells in their tracks."Identifying these genes will make it possible to see which patients have T cells that respond to alpha-synuclein and which do not," Professor Cecilia Lindestam Arlehamn, of La Jolla Institute for Immunology (LJI), said.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.The researchers suggest these clumps may be the kiss of death for dopamine-producing neurons. 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."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," Arlehamn said.
"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," added LJI Professor Alessandro Sette, from the Institute's Center for Autoimmunity and Inflammation.
One important gene expressed that the scientists found in blood samples was 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," Sette said.Going forward, 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 recognised by T cells in individuals with Parkinson's disease.