Dr. Matthew Farrer presents to attendees of WPC 2013 in Montreal.
The 3rd World Parkinson Congress (WPC) in Montreal was a great place for scientists, health professionals and the public who share an interest in Parkinson’s to share ideas, learn about recent progress and showcase the latest research discoveries with colleagues from around the world. It would be impossible for one person to attend and cover all topics due to the full slate of parallel sessions, so we’ve keyed in on some of the most exciting topics and prominent presenters at WPC 2013. Suffice to say, there was something for everyone!
Leading the way and quite active in many panel discussions, plenary sessions and media briefings was Dr. Virginia Lee, Professor at the University of Pennsylvania School of Medicine. Dr. Lee’s research into alpha-synuclein and its role in Parkinson’s disease may lead to a more complete understanding of how PD populates the different regions of the brain over time.
“In the 80’s and 90’s scientists put fetal stem cells into the brains of Parkinson’s patients to replace compromised dopamine pathways. After the patients died, their brains were studied. New cells created from the fetal stem cells were found to accumulate alpha-synuclein containing Lewy bodies,” said Dr. Lee.
Alpha-synuclein is a protein primarily found in neural tissue where it plays a role in nerve cell communication. Lewy bodies are abnormal aggregates of alpha-synuclein protein that develop inside nerve cells in Parkinson’s disease.
“We did experiments that involved putting abnormal alpha-synuclein aggregates in normal mice. We could demonstrate that mice get the alpha-synuclein pathology and pass it on to other cells, including the cells that make dopamine. These mice developed Lewy bodies. With this experiment we have generated a great model of non-inheritable Parkinson’s disease that links alpha-synuclein pathology and the loss of cells that make dopamine. Moreover, we showed that progression of Parkinson’s disease could be due to cell to cell transmission of alpha-synuclein pathology” added Dr. Lee, who has attended all three WPC events.
Dr. Lee believes this could eventually lead to Parkinson’s treatments and possibly even as an early diagnostic tool. She feels confident that eventually they will be able to block the pathology that passes misfolded alpha-synuclein from one cell to another by using antibodies or other transfer inhibitors, although no research has been done as yet leading in this direction.
“Alpha-synuclein is found in neurons in the central nervous system. It’s also found in the neurons of the gut and red blood cells. Doctors can measure alpha-synuclein levels in spinal fluid to see if they can see changes. I think any decrease in alpha-synuclein is bad. It’s still early but we’re trying to standardize using alpha-synuclein as a biomarker,” Dr. Lee said enthusiastically.
Dr. Lee also feels that this positions Parkinson’s disease and related research front and centre in the neurological sciences community. She hopes it will lead to more testing and clinical trials by teams advancing what we know surrounding alpha-synuclein.
“This puts Parkinson’s disease ahead of other neurodegenerative diseases because of these findings. Lewy bodies are abnormal structures that accumulate as trash in the brain of people with Parkinson’s. We want to model it in mice so we can do experiments for better understanding of how Lewy bodies spread over time and cause neurons to become dysfunctional and die. These insights will allow us to develop therapies to halt the spread and rescue neurons from dying,” summarized Dr. Lee.
Over time, Dr. Lee’s research will complement other studies and eventually give scientists a complete picture or map of how Parkinson’s works from start to finish. Another such researcher committed to solving the Parkinson’s puzzle is Heidi McBride through her study of mitochondria.
Mitochondria are known in scientific circles as “cellular power plants” because they generate most of any given cell’s supply of adenosine triphosphate (ATP) which is used as a source of chemical energy. Mitochondria are also involved in signaling, cellular differentiation, cell death, as well as the control of the cell cycle and cell growth. One of the biggest developments in Parkinson’s research is that the mitochondria become dysfunctional in the early stages of the disease.
A well-functioning engine
“Think of it as a combustion engine. Mitochondria use oxygen we breathe along with fuel (sugar and fat) but unfortunately you get ‘smoke’ with an engine malfunctioning from Parkinson’s disease. We have to figure out how mitochondria clean themselves and remove bad proteins and lipids,” said Dr. Heidi McBride, Canada Research Chair in Mitochondrial Cell Biology and researcher at the Neuro at McGill University in Montreal.
The next step for McBride, who recently moved to McGill to be closer to clinicians and people with Parkinson’s, is to translate the findings into clinical data with the help of her research team. To date, only McBride and Dr. Edward Fon, Director of the McGill Parkinson Program, have witnessed normal mitochondria ejecting ‘pods’ of damaged materials, a function that becomes hindered by Parkinson’s.
“We hope to find a way to accelerate the clearance of damaged mitochondria in cells so they can stay healthy. Even toxins bind and block mitochondrial respiration so you end up with additional damage from this as well. We have to find a way to get rid of this damage. We’re still working on how they (mitochondria) clean themselves and sort out the damaged bits,” added McBride.
McBride is optimistic that they are getting closer to providing answers which could lead to treatments for people with Parkinson’s.
“It’s not going to help symptoms at this point but if we could develop a drug that stops mitochondrial damage we could help those cells live longer,” McBride said.
Molecular therapeutics targeted to the right pathways in the right subjects
Dr. Matthew Farrer, Professor in the Department of Medical Genetics and Director of the Centre for Applied Neurogenetics in the Brain Research Centre at University of British Columbia and the 2012 Donald Calne Lectureship recipient, is working towards similar breakthroughs with his research on genetics, neuroscience, neurology and their integration with Parkinson’s disease.
“We’re working on finding new genes, mutations, pathways, mechanisms and new insights on how to fix the problem of Parkinson’s disease,” said Dr. Farrer.
Like his colleagues, Dr. Farrer is looking for ways to treat and even cure Parkinson’s at the molecular level.
“Our belief is that our work will lead to medications that slow or even halt disease progression, specifically with molecular therapeutics targeted to the right pathways in the right subjects,” Dr. Farrer added.
Together, Dr. Virginia Lee, Dr. Heidi McBride, Dr. Matt Farrer and other leaders in the neurosciences are helping to build a complete map of the biology of Parkinson’s disease. This is a large map and a global effort.
“We’ve got to keep on doing what we do. By 2020 we hope to have mapped almost all of the genetic variability contributing to Parkinson’s. We’re making models from that and are now starting to get insights about the biology,” Dr. Farrer finished.
To stay up to date on the work of the three researchers featured in this article, read more online (original content in English only) at:
Dr. Virginia Lee , Dr. Heidi McBride , Dr. Matthew Farrer
To find out more about Parkinson Society Canada’s National Research Program, visit online at www.parkinson.ca.