Cell-Signaling Inhibitor May Halt Progression Parkinson's Disease Progression

In a recent study, researchers found that oral administration of AZD1480, a JAK/STAT pathway inhibitor known as Jakinibs, decreased destructive inflammation and nerve cell degradation in the part of the brain affected by Parkinson’s disease. Presently, there is no way to prevent the progression of Parkinson’s disease.

"We believe Jakinibs may become a viable therapeutic option for Parkinson's disease patients," said study lead author Etty Benveniste, PhD. "They are already being studied for other conditions, are orally bioavailable, seem to be well-tolerated, and do not promote troublesome immunosuppression. Furthermore, there may also be other ways of targeting the JAK/STAT pathway as a neuroprotective therapy for neurodegenerative disease."

A variety of Jakinibs are in phase 1, 2, or 3 trials for other diseases, according to the study published in The Journal of Neuroscience.

"This is a very important advance," said researcher David Standaert, MD, PhD. "It shows that anti-inflammatory strategies have real potential. The next steps will be to validate some of the inflammatory changes seen in the animals in patients with Parkinson's disease, which in turn will enable planning of clinical studies of anti-inflammatory therapies in patients with Parkinson's."

In the study, researchers challenged rat immune cells in vitro either with aggregated human α-synuclein, or induced overexpression of α-synuclein carried by a virus vector in their brains.

Untreated, neuroinflammation and degradation of dopamine-producing neurons occurs in the substantia nigra, the part of the brain marked by cell death in Parkinson’s.

The accumulation of α-synuclein is a core aspect of Parkinson's disease and leads to the activation of the brain immune cells, production of inflammatory signaling chemicals, and neurodegradation.

Researchers found that both in vitro and in vivo experiments showed AZD1480 stopped JAK/STAT activation and downstream gene induction after a challenge by α-synuclein, according to the study.

Genes that are induced by α-synuclein are associated with the proinflammatory phenotype if they are not induced by α-synuclein and AZD1480. This inhibition was seen to lessen innate and adaptive immune responses.

Researchers concluded the results of the study show that Jakinibs has the potential to protect against degradation of dopamine-producing neurons.