Essential Science: Halting neuronal loss in Parkinson’s disease

Dec 3, 2018     BY TIM SANDLE  

A new drug aims to freeze Parkinson's disease in its tracks. The drug targets neuroinflammation, and researchers think this could halt further neuronal loss in Parkinson’s disease.

Brain inflammation is present in brains of autistic patients. — Neurons often have extensive networks of dendrites, which receive synaptic connections. Shown is a pyramidal neuron from the hippocampus, stained for green fluorescent protein.

Wei-Chung Allen Lee, Hayden Huang, Guoping Feng, Joshua R. Sanes, Emery N. Brown, Peter T. So, Elly

Parkinson’s disease is a degenerative disorder of the central nervous system. It is triggered by alpha-synuclein aggregates. With Parkinson’s disease brain cells exhaust themselves and die prematurely. Symptoms of the disease include hand shaking or difficulty walking. Some ten million people are affected by the disease worldwide. 

Parkinson’s disease is complex, with the main factor being the loss of dopaminergic neurons in the substantia nigra, which is a structure located in the midbrain. This neuron loss is, according to Biotechniques, accompanied by chronic neuroinflammation, dysfunctional mitochondria and the formation of alpha-synuclein protein rich Lewy bodies. Lewy bodies are abnormal aggregates of protein that develop inside nerve cells.

Despite these known factors, the the processes that combine to connect each pathological factor together remains unknown. This means research into the condition is based on a variety of different approaches. One area of research is with the immune system, and this is the focus of a new study from Australia.

Researchers from The University of Queensland have located an important immune system called the NLRP3 inflammasome. This system can be triggered by dopaminergic loss. Further analysis revealed a tiny molecule caled MCC950, which can target the NLRP3 system. In animal trials, the molecule was shown to halt further development of Parkinson's disease.

According to the principal scientist Dr. Trent Woodruff: “we found a key immune system target, called the NLRP3 inflammasome, lights up in Parkinson’s patients, with signals found in the brain and even in the blood. MCC950, given orally once a day, blocked NLRP3 activation in the brain and prevented the loss of brain cells, resulting in markedly improved motor function.”

https://youtu.be/kL5fIhejxxE

The approach taken is different to most approaches taken to treat the disease, which center on seeking to block neurotoxic proteins that build up in the brain. The new research seeks to tackle immune cells in the brain called microglia, which can potentially clear away the toxic proteins.

The outcome of the research is that the molecule shows promise as a new therapy for Parkinson's disease, and it has the potential to stop the disease in its tracks. This will of course require further research , including more animal studies before any human trials are considered. However, Phase 1 clinical trials could begin as early as 2019.

Research paper The research has been published in the journal Science Translation Medicine. The research paper is titled: "Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice."

http://www.digitaljournal.com/tech-and-science/science/essential-science-halting-neuronal-loss-in-parkinson-s-disease/article/538147