The Parkinson’s research community is publishing thousands of articles every year. Each article marks a step forwards, sideways and sometimes backwards in the quest for knowledge.
The majority of articles are first published in subscription journals, behind a “paywall”. This is not the place to argue the merits of this system. Suffice to say that it is unpopular but very successful. The Open Access movement, for example AMRC Open Research is bringing an increasing amount of work to free and full availability straightaway.
However, availability does not change the fact that most articles are impenetrable to the layman. We therefore rely on comptetent commentators to assess the importance of the information and express it in plain English. The nature of Parkinson’s means that this field of medicine and disease therapy is littered with personal and commercial agendas. There are also charlatans at work. The PenPRiG team use their experience of the reliable commentators and organisations to navigate to reliable information.
Our world increasingly gets its news and knowledge from videos on smartphones. There is a flood of video material on all aspects of research from basic biology through to how best to live with Parkinson’s.
This is our current selection. Inevitably it is a very small slice of what is out there, so if you think something significant is missing, please use the Feedback form.
Reviews and Summaries
A VERY comprehensive look ahead to 2019 by Simon Stott, one of our most respected commentators and educators.
The Cure Parkinson’s Trust Review of 2018 covers the projects they are concentrating on.
Another look back, this is a simply expressed and brief review of the research highlights from the Parkinson’s UK perspective.
Ben Stecher is one of the most active Advocates in the PD world. He reports his impressions of an event sponsored by the Sergey Brin Foundation in Notes from the Aligning Science Across Parkinson’s Workshop. Sergey co-founded Google and has both a family connection to Parkinson’s and wealth.
Parkinson’s was once thought not to have genetic causes. In 1997 mutations in one particular gene were shown to be responsible for a form of Parkinson’s in some families. Over the following 30 years some 20 genes have been identified in various inherited forms of Parkinson’s.
Even so, inherited Parkinson’s remains in the minority. Estimates range from 15% to 25%, the balance being the Idiopathic diagnosis. This term is best understood as the medical dictionary entry for “don’t know”.
The majority of people have Parkinson’s for so far unexplained reasons, but the basic mechanisms are shared amongst all. The neurodegeneration that is at the root of Parkinson’s is a result of the loss of signals between brain cells. The genetic cases have enabled a vast amount of research into the mechanisms that are causing this loss of signal.
The Not bohemian, just ‘Rapsodi’ study is looking at people with the GBA gene risk factor and who also demonstrate the early signs of Parkinson’s. The GBA gene was the topic for Dr. Stephen Mullin’s inaugural talk for the PenPRiG Meet The Researcher programme.
The LRRK2 (“Lark two”) gene is another villian of the piece. The Michael J Fox Foundation brought together otherwise competing companies to demonstrate that drugs that (in essence) switched off this faulty gene were safe for human use. They are part-funding the Denali Phase 1b clincal trial.
Outside the genetic sphere the causes of Parkinson’s are the subject of much speculation. What makes the brain susceptible is not at all clear, and until relatively recently our understanding of how Parkinson’s attacks the brain was limited to post mortem examination of the brain. The root cause of degenerative diseases of the brain is, by definition, the death of cells. The differences between the diseases are marked out by which part or parts of the brain are affected and by the rate of progression. By progression we actually mean deterioration.
The research knowledge base is expanding rapidly through the development of animal models and advances in biotechnology. However, the detailed biological mechanisms of Parkinson’s are still the subject of much research effort and argument. A great deal of research activity is concerned with basic biology, where the opportunity for interaction with members of the general public is distinctly limited. From basic biology springs the development of drugs, or “compounds” as they are called in the business.
PenPRiG classifies the research activity that is relevant to our purpose in two ways,
- “Treatment”. By treatment we mean the use of compounds to try and slow down, stop or reverse the progression of the disease. Examples include stem cell therapy and re-purposed drugs.
- “Management”. By management this we mean drugs, and therapies where the intention is to maintain or improve the experience of living with Parkinson’s. Examples are Levodopa, technologies such as Direct Brain Stimulation, and exercise programmes.
What are the mechanisms that cause the cells to die? Needless to say there are different types of cell and different processes, but again for the purposes of classification we can simplify an otherwise very complex situation by considering only the objectives of Treatment. All our conscious movements, and unconscious processes such as breathing are enabled by neurones creating or responding to electrical signals between each other. Everything else in the brain can be regarded as the Support Crew.
Treatment addressed to the neurons – Nurturing The Neurons – may for example be focused on the mechanism that charges the internal batteries of neurons that fire the signals.
In the normal course of events cells die. Our skin cells are continuously shed. The same is true within the brain, amplified by the life cycle of the cells that service the electrical activity. The most widely held view at present of the cause of Parkinson’s is that by not Removing The Rubbish, the accumulation of dead material suffocates the neurons.
Nurturing the neurons and removing the rubbish are treatments intended to slow down and preferably stop the progress of Parkinson’s. The more radical treatments seek to refresh or rejuvenate the neuron population, thereby restoring normal brain function.
Stem cell therapy is the most newsworthy treatment strategy, attempting to refresh the relevant neuron population. In certain parts of the brain, new neurons are developed, but not where they are needed. There is no evidence that neurons are spontaneously developed in the parts of the brain concerned with Parkinson’s. However, an alternative treatment strategy of refreshing the Support Crew (the GDNF Trial) shows the promise of new neuron growth in the places where it counts.
These approaches may not bring a complete return of function since any collateral damage would not be repaired, but otherwise is are are arguably a Cure for Parkinson’s.
Several newly-created drugs have failed in clinical trials. The costs, timescales and processes for candidate drugs development are all increasing. As a result there has been a significant shift in the direction of research to the possibilities for using drugs already approved for other treatments.
This is a July 2018 review of the safety and potential efficacy of the most promising candidate drugs. Iin the avanced stages of clinical testing.
Stem cell therapy
Cure Parkinson’s Trust’s Stem Cell Research Update looks at the beguilingly simple idea of replacing the neurons that we have lost with new ones. Simple, but already the graveyard of major studies. An ethical minefield until recently, and technically very challenging. Nevertheless for all sorts of reasons the work continues. Unfortunately this is also the focus of charlatans.
Those of us some way down the road of understanding our condition will have considered taking part in a clinical trial. PenPRiG’s purpose is to promote local opportunities. We share knowledge about the clinical trial process as it is today and views as it perhaps should be tomorrow.
“Informed Consent” is central to participation in a trial. Introducing Clinical Trials Highlights explores the issues.
We are getting more sophisticated and targeted with our clinical trials for Parkinson’s, gradually moving away from the days when a drug was tested on anyone in the Parkinson’s-affected community.
The Gretchen Amphlett Lecture 2018 , in particular look out for Dr Simon Stott, regarding his research on breath analysis technology being used to identify people with Parkinson’s. At that time a Research Associate at the University of Cambridge, he is now Deputy Research Director at The Cure Parkinson’s Trust