In the Parkinsonian brain, there is a severe reduction in a substance called dopamine. Reduced levels of this chemical are associated with the appearance of the motor features of Parkinson’s.
Dopamine replacement therapies has been the front line therapy for the condition for the last 50 years. But long-term use of drugs like L-dopa are associated with the rise of motor complications, like dyskinesias.
In the an effort to correct this, researchers in France have recently developed a method of continuously and directly delivering dopamine to the brain. They have now published the results of a study evaluating the safety and feasibility of this approach in a primate model of Parkinson’s.
In today’s post, we will discuss what dopamine is, review the results of this new research, and explore what might happen next for this new potential treatment method.
Prof David Devos. Source: Youtube
This is Dr David Devos.
He is Professor of medical pharmacology at University of Lille (France), world-renowned Parkinson’s researchers, a passionate advocate for the Parkinson’s community, and on top of all that he’s a really (and I mean REALLY) nice guy as well.
Recently, his research group (in collaboration with other scientists) published a report presenting a novel way of treating Parkinson’s, that he is now hoping to take to the clinic.
Here is the report:
Title: Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson’s disease.
Authors: Moreau C, Rolland AS, Pioli E, Li Q, Odou P, Barthelemy C, Lannoy D, Demailly A, Carta N, Deramecourt V, Auger F, Kuchcinski G, Laloux C, Defebvre L, Bordet R, Duce J, Devedjian JC, Bezard E, Fisichella M, David D.
Journal: Neurobiol Dis. 2020 Mar 20:104846.
PMID: 32205254 (This report is OPEN ACCESS if you would like to read it)
In this study, the researchers wanted to explore how to directly deliver a chemical called dopamine to the brain.
What is dopamine?
I have been extremely reluctant to write a post on this topic because the nature of it is well outside of my circle of confidence. But many concerned readers have emailed me about the current SARS-CoV-2/Covid-19 crisis asking questions.
Specifically, they want to know if people with Parkinson’s are more at risk and what can be done.
My answers to these emails has been very simple: There simply isn’t enough data to know at present if people with Parkinson’s are more vulnerable, but there is ample historic evidence to suggest that social distancing is a very good course of action.
In today’s short post, we discuss the SARS-CoV-2/Covid-19 situation.
Crystal Mill, Gunnison County, Colorado. Source: Pinterest
In 1918, as the young men of America returned from the Great War in Europe, they brought with them a terrible souvenir: Influenzia (or “The Spanish flu”).
By early October of that year, the virus had made its way across the midwest and it had reached the great state of Colorado. And on the 8th October – sensing the invisible enemy closing in – the officials in the sparsely populated mountainous Gunnison County (Colorado – pop. 5,600), isolated themselves off from the rest of the world. They immediately closed all of their schools, and insisted visitors undergo a five-day quarantine before being allowed to walk their streets.
Gunnison 1918. Source: 9News
Barricades with lanterns went up on the major highways. They carried warning signs instructing drivers to pass straight through the county without stopping. Absolutely no interaction between these visitors and the local residents was allowed. And anyone getting off a train at the main station was immediately put into mandatory quarantine.
The county maintained the quarantine order until the morning of February 5th, 1919 (4 months). The economy suffered, but the community survived – during that period of isolation, only two people in the entire county got the flu (one of whom passed away – Source).
The point of this historical tale is that social distancing is a very good defence in a pandemic.
The goal is to simply deprive a virus of any opportunity to move from person-to-person.
Perhaps the residents of “sparsely populated” Gunnison county just got lucky?
Given that the condition is defined by the loss of specific types of neurons in the brain, any future therapy for Parkinson’s should include some form of restorative treatment. Much of the current clinical research exploring restoration in Parkinson’s is focused on cell transplantation – replacing the cells that have been lost in the brain.
But the adult brain is very different to the developing brain. While youngsters have lots of nurturing and supportive protein floating around – encouraging plasticity and survival – once we reach adulthood, our brains appear to be full of inhibitory molecules that reduce rejuvenation in the case of injury.
What if we could re-introduce some of those supportive factors and remove the inhibitory proteins? Could this help with restorative therapies for Parkinson’s?
In today’s post, we will look at new research exploring how we may be able to reduce some of those inhibitory factors and provide a more supportive environment for restorative therapy in Parkinson’s.
As we regularly state here on the SoPD, any ‘curative therapy’ for Parkinson’s is going to require three core components:
- A disease halting mechanism
- A neuroprotective agent
- Some form of restorative therapy
Now, the bad news is (as far as I am aware) there is no single treatment currently available (or being tested) that can do all three of these things. By this I mean that there is no disease halting mechanism therapy that can also replace lost brain cells. Nor is there a restorative therapy that stop the progression of the condition.
That statement can obviously be read as bad news, but it shouldn’t.
Let me explain:
A curative therapy for Parkinson’s is going to need to be personalised to each individual, with varying levels of each of the three component listed above. It will be a multi-modal approach designed for each individual’s needs.
Making things personal. Source: Flickr
By this I mean, there is a great deal of heterogeneity (or variability) between individuals with regards to their symptoms and the amount of time that they have had the condition. Some folks are more tremor dominant, while others do not experience tremor at all. Likewise, some individuals have only just been diagnosed, while others have lived with the condition for many years.
The treatment needs of each individual will be different, and thus what we will require is different amounts of the disease halting mechanism component, the neuroprotection component, and the restorative therapy components for each affected person.
In today’s post we are going to explore some alternative approaches being tested for restorative therapy.
What do you mean ‘alternative’?
New research from multiple independent research groups proposes that one Parkinson’s associated protein (LRRK2) may be affecting the activity of another Parkinson’s associated protein (GCase).
Specifically, when LRRK2 becomes hyperactive (as is the situation in some cases of Parkinson’s), it causes is associated with a reduction in the amount of GCase activity.
In today’s post, we will discuss what LRRK2 and GCase both do, what the new research suggests, and how this news could influence efforts to treat Parkinson’s in the future.
Connections. Source: Philiphemme
For a long time, the Parkinson’s research community had a set of disconnected genetic risk factors – tiny errors in particular regions of DNA that were associated with an increased risk of developing Parkinson’s – but there seemed to be little in the way of common connections between them.
Known genetic associations with PD. Source: PMC
The researchers studied the biological pathways associated with these risk factors, trying to identify potential therapeutic angles as well as looking for connections between them.
The therapies are currently being clinically tested (Click here to read more about these), but the connections have taken a lot longer to find.
Recently one important connection has been identified by several research groups and it could have important implications for how Parkinson’s will be treated in the future.
What’s the connection?
Researchers from Düsseldorf (Germany) and a biotech company in San Francisco have published a research report in which they present evidence that the H1N1 influenza A virus can cause the Parkinson’s-associated protein alpha synuclein to start aggregating in neurons (both in cell culture and mice).
In addition, they reported that an influenza drug blocked this aggregation effect.
In today’s post, we will discuss what H1N1 influenza virus is, what the new research report found, and we will consider what this means for Parkinson’s.
The date today is the 11th March, 2020.
Based on the news headlines trending on all forms of media, it is probably the absolute worse moment to consider writing a post about how a particular viral infection could be playing a role in Parkinson’s,… but here we are.
Over night a research report was published that immediately grabbed my attention.
This is the report:
Title: Disruption of cellular proteostasis by H1N1 influenza A virus causes α-synuclein aggregation.
Authors: Marreiros R, Müller-Schiffmann A, Trossbach SV, Prikulis I, Hänsch S, Weidtkamp-Peters S, Moreira AR, Sahu S, Soloviev I, Selvarajah S, Lingappa VR, Korth C.
Journal: Proc Natl Acad Sci U S A. 2020 Mar 9. pii: 201906466. [Epub ahead of print]
In this study, the researchers reported that infection by the H1N1 influenza A virus (very different to the current coronavirus COVID-19) can cause accumulation and aggregation of the Parkinson’s-associated protein alpha synuclein.
Remind me, what is H1N1 influenza?
In 2019, researcher from around the world gathered for a special meeting in Toronto (Canada) to discuss/debate some of the most important issues slowing Parkinson’s research.
Specifically, they asked if Parkinson’s is not a single condition, but rather a collection of diseases that look very similar, can current research efforts be revised to cater for this shift in definitions, or does Parkinson’s research need to be reconstructed?
Recently a summary of the discussions at the meeting has been published.
In today’s post, we will review that summary document, explore some of the topics discussed, and consider some of their proposed solutions.
Let’s start this post with a simple question: What are the first principles of Parkinson’s?
What do you mean “first principles”?
First principles are what philosophy and engineering types considered the most basic propositions (or assumptions) that cannot be deduced from any other propositions or assumptions.
Simply, they are the fundamental facts from which everything else stems.
Elon Musk likes to talk about first principles in all of his projects, and on all matters he suggests we should : “boil things down to their fundamental truths and say, ‘What are we sure is true?’… and then reason up from there, as opposed to reasoning by analogy”.
What is meant by ‘analogy’ here?
Analogy refers building knowledge and solving problems based on prior assumptions; using beliefs widely held and approved by a majority of people. It allows you to take your understanding of one domain and compare (or apply) it with another.
The example of analogy is that it is easier to teach students that electrons whizz around an atom’s nucleus the same way planets orbit the sun because they will have been exposed to this idea, than actually explaining the intricacies of nuclear physics…even though there are more than a few differences.
Let’s return to the initial question though: What are the first principles of Parkinson’s?
I don’t know. Are you going to tell me?
Nope. I don’t know either.
Ok. Um. So is this going to be a really short SoPD post then?
Recently Parkinson’s researchers around the world have been calling for efforts to establish the “first principles” of Parkinson’s (and Parkinson’s is not alone here – neurodegenerative research in general is going through a similar period of self reflection – click here to read more about this in Alzheimer’s).
A good example of this process is what happened in Toronto last April.
What happened in Toronto?
At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during February 2020.
The post is divided into seven parts based on the type of research:
So, what happened during February 2020?
In world news:
February 5th – A research team in Hong Kong announced the development of a droplet-based electricity generator, which will allow electrical energy production with the minimum possible use of water (Click here to read more about this).
February 9th – Storm Ciara battered the UK.
February 12th – Researchers discovered a new group of antibiotics that display a unique approach to attacking bacteria, providing a promising new approach in the fight against antimicrobial resistance (Click here to read more about this).
February 24th – Michael Jordon’s tribute to the late Kobe Bryant almost made me cry (almost!). It’s a beautiful speech for a basketball fan.
February 26th – Astronomers announced that Earth had acquired a second, slightly smaller moon. Designated 2020 CD3, a calculation of its orbit suggests that it has been orbiting Earth for approximately 3 years. But given that it is the size of a car, don’t expect a second moon landing any time soon (Click here to read more about this).
In the world of Parkinson’s research, a great deal of new research and news was reported:
In February 2020, there were 921research articles added to the Pubmed website with the tag word “Parkinson’s” attached (1803for all of 2020 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).
The top 5 pieces of Parkinson’s news
Neurotrophic factors are naturally occuring proteins that help to keep neurons alive, provide a supportive environment, and encourage growth.
For a long time, researchers have been exploring methods of utilising the power of neurotrophic factors in regenerative strategies for neurodegenerative conditions, like Parkinson’s.
Today, the biotech firm Herantis Pharma announced topline results of their Phase 1/2 clinical trial of the neurotrophic factor Cerebral Dopamine Neurotrophic Factor (or CDNF).
In today’s short post, we discuss what CDNF is, explore what the trial involved, and consider what the
It is cold this time of year in Helsinki, but there will be some warm smiles there today.
A small biotech firm called Herantis Pharma has announced the topline results of their Phase 1/2 clinical trial exploring the safety and tolerability of a treatment called CDNF.
What is CDNF?
There is a lot of clinical and biological similarities between the neurodegenerative conditions of Parkinson’s and multiple systems atrophy (or MSA).
Recently, however, researchers have published a report suggesting that these two conditions may be differentiated from each other using a technique analysing protein in the cerebrospinal fluid – the liquid surrounding the brain, that can be accessed via a lumbar puncture.
Specifically, the method differentiates between different forms of a protein called alpha synuclein, which is associated with both conditions.
In today’s post, we will look at what multiple systems atrophy (MSA) is, discuss how this differentiating technique works, and explore what it could mean for people with either of these conditions.
Getting a diagnosis of Parkinson’s can be a tricky thing.
For many members of the affected community, it is a long and protracted process.
Firstly, there will be multiple visits with doctors and neurologists (and perhaps some brain imaging) until one is finally given a diagnosis of PD. There are a number of conditions that look very similar to Parkinson’s, which must be ruled out before a definitive diagnosis can be proposed.
But even after being diagnosed, there are a group of conditions that look almost identical to Parkinson’s. And many people will be given a diagnosis of Parkinson’s before they are then given a corrected diagnosis of one of these other conditions.
Can you give me an example of one of these other conditions?
Sure. A good example is multiple systems atrophy.
What is Multiple System Atrophy?
The results of a small clinical study evaluating the safety and tolerability of Ursodeoxycholic acid (or UDCA) in people with Parkinson’s have recently been published.
UDCA is a naturally occurring bile acid that is used in the treatment of gallstones. More recently, however, researchers have reported that this clinically available medication has beneficial effects in models of Parkinson’s.
The clinical study that has recently been published suggests that UDCA is safe and well tolerated in people with Parkinson’s, and warrants further investigation in larger clinical trials.
In today’s post, we will discuss what UDCA is, we will consider some of the previous research in models of Parkinson’s, we will review the results of the clinical trial, and then we will discuss what may happen next.
How often do you consider your gallbladder?
Your gallbladder. How often do you think about it?
And I would believe that. It is one of the less appreciated organs. A pear-shaped, hollow organ located just under your liver and on the right side of your body. Its primary function is to store and concentrate your bile. What is bile you ask? Bile is a yellow-brown digestive enzyme – made and released by the liver – which helps with the digestion of fats in your small intestine (the duodenum).
One of the down sides of having a gall bladder: gallstones.
Gallstones are hardened deposits that can form in your gallbladder. About 80% of your average gallstone is cholesterol. The remaining 20% of a gallstone is made of calcium salts and bilirubin. Bilirubin is the yellow pigment in bile. When the body produces too much Bilirubin or cholesterol, gallstones can develop.
Gallstones – ouch! Source: Healthline
About 10-20% of the population have gallstones (Source), but the vast majority experience no symptoms and need no treatment.
Interesting intro, but what does any of this have to do with Parkinson’s?
One of the treatments for gallstones is called UDCA. And recently we learned the results of a clinical trial in which UDCA is being “repurposing” as a treatment for Parkinson’s.
What is UDCA?