The Immune System in Parkinson’s Disease: A Possible Target for Treatment

The Immune System in Parkinson’s Disease: A Possible Target for Treatment

By Marianne von Euler

Parkinson’s disease is the second most widespread neurodegenerative disorder in the world, after Alzheimer’s Disease. Parkinson’s affects around 7 to 10 million people worldwide and occurs in all races but with a predominance for Caucasians. Men are 1.5 times more likely to develop the disease than women.

What Are the Symptoms of Parkinson’s Disease?

Parkinson’s disease is considered a movement disorder characterized by four cardinal motor symptoms: rigidity, slow movements, postural instability and tremors. During the last decade, it has become clear that Parkinson’s disease is a very complex disorder with non-motor symptoms occurring prior to the motor symptoms; some of these involve speech problems, decreased sense of smell, depression, sleep disturbances and constipation (among others).

The motor symptoms are attributed to the loss of dopamine-producing neurons in a region of the brain called the substantia nigra, responsible for controlling movements. The classical feature of the disease is the formation of aggregates of a protein called alpha-synuclein. These aggregates are termed Lewi bodies.

How Does the Immune System Contribute to the Disease?

Most neurodegenerative diseases, including Parkinson’s, involve inflammatory processes (usually referred to as neuroinflammation) that causes neuronal cell death and aggravates the disease. It has been shown that in Parkinson’s, neuroinflammation can engage both the innate and adaptive immune system, driven by the activation of microglia (the brain resident macrophages); there is also a local invasion of circulating immune cells that produce a wide range of immune proteins such as cytokines and chemokines. The disease severity is directly correlated with microglial activation.

However, there is a subset of immune cells that are beneficial and protect the neurons from dying due to the ongoing inflammation. These cells are called regulatory T cells (Tregs) and have been shown to infiltrate into the brain during disease and control the activation of microglia.

Current Treatment Options

Several scientific groups have explored the possibility of using the immune system as a target for the treatment of Parkinson’s disease. Vaccinations using alpha-synuclein or antibodies against this protein have shown very promising results in terms of reducing inflammation and protecting neurons from dying and ameliorating motor symptoms. Several animal models have shown that using alpha-synuclein as a vaccine leads to the infiltration of Tregs into the brain causing a reduction of the pathological burden and vaccination with antibodies against alpha-synuclein target and aid the clearance of the toxic aggregates by microglia.

Yet, it is important to translate these findings to humans. Currently, there is a phase-two clinical trial for a vaccine from the Austrian pharmaceutical company AFFiRiS; this vaccine was developed to induce the formation of antibodies against alpha-synuclein and has shown a reduction in the levels of the cerebral protein and an amelioration of the neuropathological alterations such as neuronal cell loss.

Perhaps the key to face the disease could be linked to the modulation of the immune system or, at least, be helpful in alleviating some of the main symptoms.

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