IMPROVED treatment for Parkinson’s disease could be on the horizon following successful trials of a new drug that can treat the condition by changing the behaviour of immune cells so that they protect dopamine-protecting cells instead of attacking them.
Ten years ago, researchers made the discovery that white blood cells have a propagatory role in the development of Parkinson’s disease through the destruction of neurons, mainly in the substantia nigra pars compacta. From this research, the idea that the behaviour of these immune cells could be altered for neuroprotection was born. Recent studies have now identified a suitable candidate for the role: LBT-3627, an experimental drug similar to the endogenous anti-inflammatory molecule, vasoactive intestinal peptide (VIP).
While it has long been accepted that Parkinson’s disease involves changes to both dopamine and non-dopamine neurons and their cell signalling pathways, as well as the infiltration of T lymphocytes and inflammation of microglia, controversy remained regarding the exact mechanism and effect of these changes. Initially, theories suggested that these existing changes were a result of injury; however, more recent dogma suggests that activated microglia and white blood cells play a significant role in the Parkinson’s-related neurodegeneration.
Knowledge of the role of inflammation in Parkinson’s has been the impetus for new drug targets, such as VIP-based molecules. However, VIP rapidly degrades in the body, and is unable to distinguish between its two natural receptors: VPAC1 and VPAC2. LBT-3627 is an agonist specific to VPAC2, with a longer shelf-life in the body. It also has the bonus of possible oral administration in the future, making it more accessible to patients with Parkinson’s disease.
LBT-3627 has proved effective in murine models, where it afforded protection to up to 80% of dopamine-producing cells by initiating change in the microglial cells. These changes halted the progress of Parkinson’s disease.
”The key finding in our study was that a specific white blood cell subset was produced as a consequence of LBT-3627 treatment and provided protection of dopamine-producing nerve cells from being damaged. The neurotoxic immune reaction was halted and LBT-3627 was able to prevent disease,” concluded Prof Gendelman, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA.
While testing is ongoing, the researchers are extremely positive, and a Phase I clinical trial of LBT-3627 is expected in 2017.