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?
Continue reading “Going viral”
Canadian scientists recently reported that mice with a specific genetic variation – in the Parkinson’s-associated LRRK2 gene – differ in how they are able to deal with bacterial and viral infections.
Curiously, mice with the Parkinson’s-associated LRRK2 mutation could handle a bacterial infection better than normal mice, while mice with no LRRK2 protein struggled against the infection. And the researchers found that this effect was most prominent in female mice in particular.
And curiously, when the mice are infected with a dangerous virus, female mice with the Parkinson’s-associated LRRK2 mutation fared worse than their male counterparts.
In today’s post, we will discuss what LRRK2 is, review the new research, and explore what the sex difference could mean in terms of Parkinson’s.
Autumn colours. Source: Visitsunlimited
I am a big fan of Autumn.
The colours and the crisp/bracing air. I love the long, slow afternoon strolls and anticipation of the festive season to come.
But most of all I love the license to eat all the good wintery food. After a summer of salads and light food, there is nothing better that entering a warm cottage or pub, and smelling the hearty food (my wife if French – we navigate based on the quality of eateries).
Autumn bliss. Source: Askdrake
But there is a down side to autumn: The start of the flu season.
Luckily, our immune systems are pretty robust – doing battle on a moment-to-moment basis with all manner of pathogenic agents.
Recently, some Canadian scientists discovered something interesing about the immune system and it relates to Parkinson’s.
What did they find?
Continue reading “Something LRRKing in the immune system”
Theories of viral agents as possible causal (or influencing) factors in Parkinson’s have long existed.
This week a research team from Colorado in the USA published a new report demonstrating that mice infected with a mosquito-borne alphavirus (called Western equine encephalitis virus) develop Parkinson’s-like features.
These features include the loss of dopamine neurons, increased neuroinflammation, locomotor issues, and the wide spread presence of aggregated protein (all classical hallmarks of the Parkinsonian brain).
In today’s post, we will look at what mosquito-borne alphaviruses are, what this new study found, and how the results could help us to better understand some cases of Parkinson’s.
Electron micro photograph of Influenza viruses. Source: Neuro-hemin
Between January 1918 and December 1920, there were two terrible outbreaks of an influenza virus.
The event became known as the 1918 flu pandemic.
Approximately 500 million people across the globe were infected by the H1N1 influenza virus during this period, and there were approximately 50 to 100 million associated death.
Now, to put that into perspective for you, that was basically 3-5% of the world’s population at that time.
1918 Spanish flu. Source: Chronicle
At the time, much of the world was blind to these events. Given that this pandemic occurred during World War 1, censors limited the media coverage of the pandemic in many countries in order to try and maintain some sort of morale (very thoughtful of them).
The Spanish media, however, were not censored and this is why the 1918 pandemic is often referred to as the ‘Spanish flu’.
But at the same time that H1N1 influenza virus was causing havoc, a Romanian born neurologist named Constantin von Economo noticed something interesting.
What did he notice?
Continue reading “A new reason to hate mosquitos?”
New data from researchers in Taiwan has intriguing implications for our understanding of the development of Parkinson’s.
An analysis of the enormous national medical database pointed towards towards hepatitis C viral infections as a risk factor for developing Parkinson’s.
But here is the twist in the tale: Interferon-based antiviral therapy reduces that risk back to normal.
In today’s post, we will review the new research, discuss what interferons are, explore what other research has been conducted on interferons in the context of Parkinson’s, and consider the implications of this new research for Parkinson’s.
We have learnt a great deal about Parkinson’s over the last few years via the use of “big data”.
Whether it be the analysis of vast pools of genetic information collected from tens of thousands of individuals with the condition, to analysing massive datasets of longitudinal medical information, these investigations has open new avenues of research and investigation.
For example, “big data” studies have demonstrated that those who smoke cigarettes and drink coffee have a reduced chance of developing Parkinson’s (click here to read a previous SoPD post on this topic). ‘Big data studies have also pointed towards novel therapeutic approaches (click here for a previous SoPD post highighting an example).
Recently, an analysis of medical records from Taiwan have shed new light on another potential influencer of Parkinson’s risk: Hepatitis C
What is Hepatitis C?
Continue reading “Interfering with interferons”
With the recent announcement that the STEADY-PD III/Isradipine clinical trial did not reach its primary end point (that of slowing the progression of Parkinson’s), the winds of change have shifted with calls for a focus on biomarkers and better treatments, rather than disease modification.
Recently, researchers at Michigan State University have reported a novel experimental gene thearpy method for dealing with one of the most debilitating aspects of Parkinson’s – dyskinesias.
Ironically, their approach involves the same calcium channels that Isradipine blocks.
In today’s post, we will look at what dyskinesias are, what gene therapy is, and how this new approach could be useful for people currently burdened by these involutary movements.
Dyskinesia. Source: JAMA Neurology
There is a normal course of events following a diagnosis of Parkinson’s.
Yes, I am grossly over-generalising.
And no, I’m not talking from personal experience (this is based on listening to a lot of people), but just go with me on this for the sake of discussion.
First comes the shock of the actual diagnosis. For many it is devastating news – an event that changes the course of their lives. For others, however, the words ‘you have Parkinson’s‘ can provide a strange sense of relief that their current situation has a name and gives them something to focus on.
This initial phase is usually followed by the roller coaster of various emotions (including disbelief, sadness, anger, denial). It depends on each individual.
The emotional rollercoaster. Source: Asklatisha
And then comes the period during which many will try to familiarise themselves with their new situation. They will read books, search online for information, join Facebook groups (Click here for a good one), etc.
That search for information often leads to awareness of some of the realities of the condition.
And one potential reality that causes concern for many people (especially for people with young/early onset Parkinson’s) is dyskinesias.
What are dyskinesias?
Continue reading “When disco-needs-ya, can gene therapy help ya?”
Earlier this year, a San Francisco-based biotech company – called Cortexyme – published a research report that grabbed my attention.
The study presented data supporting an alternative theory of the cause of Alzheimer’s – one in which a bacteria involved in gum disease appears to be playing a leading role – and evidence that the company’s lead experimental compound COR388 could have beneficial effects in the treatment of the condition.
While the study was intriguing, what completely blew my mind was the fact that the company had already tested COR388 in a couple of Phase I clinical trials, and since then they have initiated a large Phase II/III trial.
In today’s post, we will discuss this new theory of Alzheimer’s, look at what Cortexyme are doing, and how this could relate to Parkinson’s.
The dashed lines show associations. Source: Slideplayer
Before we start today’s post, a word on ‘associations‘.
Please remember while reading this material that association does not equate to causation.
So if I write something like “researchers have found an association between a type of bacteria that causes gum disease and Alzheimer’s”, it does not mean that someone with either condition necessarily has the other. It only means that they have both simply appeared in the same individuals at a higher than chance rate.
So what is today’s post about?
A very interesting report in which researchers have found an association between a type of bacteria that causes gum disease and Alzheimer’s.
Continue reading “I’ve got gum disease on my mind”
This post is a game of two halves.
The first half will explain the concept of a surgical procedure for Parkinson’s called ‘subthalamic deep brain stimulation‘, in which doctors permenantly implant electrodes into the brain to stimulate a region – the subthalamic nucleus. By stimulating this region with electrical impulses, doctors can provide a better quality of life (in most cases) to people with severe features of Parkinson’s.
In the second half of this post, we will look at an approach to doing the same thing,… but without the electrodes.
Rather, researchers are using gene therapy.
In today’s post, we will discuss what deep brain stimulation is, what gene therapy is, and how the gene therapy approach is having a different kind of impact on the brain to that of deep brain stimulation.
Welcome to the first half of today’s post.
It begins with you asking the question:
What is deep brain stimulation?
Deep brain stimulation (or DBS) is a treatment method that involves embedding electrodes into the brain to help modulate the brain activity involved in movement.
It is a prodcedure that is usually offered to people with Parkinson’s who have excessive tremor or debilitating dyskinesias.
First introduced in 1987, deep brain stimulation consists of three components: the pulse generator, an extension wire, and the leads (which the electrodes are attached to). All of these components are implanted inside the body. The system is turned on, programmed and turned off remotely.
Continue reading “The good, the GAD, and the not-so ugly”
This week a biotech company called Voyager Therapeutics provided an update regarding a gene therapy approach for people with severe Parkinson’s.
Gene therapy is an experimental therapeutic approach that involves inserting new DNA into cells using a virus. The introduced DNA can help a cell to produce proteins that it usually wouldn’t produce, and this can help to alleviate the motor features of Parkinson’s.
In today’s post we will discuss what gene therapy is, what Voyager Therapeutics is trying to do, and outline what their update reported.
There are 4 phases to the clinical trial process of testing new treatment for use in humans:
- Phase I determines if a treatment is safe in humans (this is conducted in an ‘open label’ manner)
- Phase II ‘double blindly’ assesses in a small cohort of subjects if the treatment is effective
- Phase III involves randomly and blindly testing the treatment in a very large cohort of patients
- Phase IV (often called Post Marketing Surveillance Trials) are studies conducted after the treatment has been approved for clinical use
(‘Open label’ refers to both the investigator and the participants in a study knowing what treatment is being administered; while ‘double blind’ testing refers to studies in which the participants and the investigators do not know whether the participant is receiving the active treatment or an inert control treatment until the end of the study).
Based on the successful completion of their Phase I clinical trials for their gene therapy treatment called VY-AADC (Click here to read more about this), Boston-based biotech firm Voyager Therapeutics approached the US Food and Drug Administration (FDA) with the goal of shifting their clinical trial programme into Phase II testing.
What is gene therapy?
Continue reading “Voyager Therapeutics update”
Today biotech company Voyager Therapeutics announced an update on their ongoing phase Ib clinical trial. The trial is evaluating the safety and tolerance of a gene therapy approach for people with advanced Parkinson’s.
Gene therapy is a technique that involves inserting new DNA into a cell using viruses. In this clinical trial, the virally delivered DNA helps the infected cell to produce dopamine in order to alleviate the motor features of Parkinson’s.
In today’s post we will discuss what gene therapy is, review the new results mentioned in the update, and look at other gene therapy approaches for Parkinson’s.
Voyager Therapeutics is a clinical-stage gene therapy company that is focused on treatments for neurological conditions, such as Parkinson’s. Today the company announced an update of their ongoing Phase 1b trial of their product VY-AADC01 (Click here to see the press release).
VY-AADC01 represents a new class of treatment for Parkinson’s, as it is a form of gene therapy.
What is gene therapy?
The gene therapy involves introducing a piece of DNA into a cell which will cause the cell to produce proteins that they usually do not (either by nature or by mutation). The DNA is artificially inserted into cells and the cell’s protein producing machinery does the rest.
How does gene therapy work?
Continue reading “Voyager Therapeutics: Phase I clinical trial update”
At the end of each year, it is a useful practise to review the triumphs (and failures) of the past 12 months. It is an exercise of putting everything into perspective.
2017 has been an incredible year for Parkinson’s research.
And while I appreciate that statements like that will not bring much comfort to those living with the condition, it is still important to consider and appreciate what has been achieved over the last 12 months.
In this post, we will try to provide a summary of the Parkinson’s-related research that has taken place in 2017 (Be warned: this is a VERY long post!)
The number of research reports and clinical trial studies per year since 1817
As everyone in the Parkinson’s community is aware, in 2017 we were observing the 200th anniversary of the first description of the condition by James Parkinson (1817). But what a lot of people fail to appreciate is how little research was actually done on the condition during the first 180 years of that period.
The graphs above highlight the number of Parkinson’s-related research reports published (top graph) and the number of clinical study reports published (bottom graph) during each of the last 200 years (according to the online research search engine Pubmed – as determined by searching for the term “Parkinson’s“).
PLEASE NOTE, however, that of the approximately 97,000 “Parkinson’s“-related research reports published during the last 200 years, just under 74,000 of them have been published in the last 20 years.
That means that 3/4 of all the published research on Parkinson’s has been conducted in just the last 2 decades.
And a huge chunk of that (almost 10% – 7321 publications) has been done in 2017 only.
So what happened in 2017? Continue reading “2017 – Year in Review: A good vintage”