Tagged: Parkinsons

Shining a light on Parkinson’s

 

NOTE: The information in today’s post should not be considered an endorsement of PhotoPharmics or the treatment they are proposing. The author of this blog has had no communication with the company. The information in this post is provided because the author has been asked by readers to discuss it.

In October 2018, at the annual International Movement Disorders Society meeting in Hong Kong, a small biotech firm called “PhotoPharmic” presented a poster entitled “Double-blind controlled trial of Spectramax™ light therapy for the treatment of Parkinson’s disease patients on stable dopaminergic therapy.”

In the poster provided the results of a study in which 45 participants with Parkinson’s were blindly treated with light therapy for 1 hour each evening over the course of 6 months. At the end of the study, the investigators found clinically meaningful improvements in the MDS-UPSDRS rating scale, as well as significant improvements in non-motor measures.

In today’s post, we will discuss what light therapy is, what this study found, and look at what PhotoPharmic plan to do next.

 


The Tasmanian “light bucket” for Parkinson’s. Source: ABC

It might come as a bit of a surprise to some readers, but one of my favourite stories of 2019 from the world of Parkinson’s research originates from Tasmania.

It is a tale that involves a group of Australian Parkinson’s advocates who somehow cottened on to a seemingly inconceivable idea (treating oneself with a homemade light bucket). But their project was embraced by the local Tasmanian community which is helping out with the research, for example the Dorset community men’s shed is helping to make the light buckets.

The Dorset community men’s shed helps to make the buckets. Source: ABC

And whatsmore they have inspired an Australia-wide “proof-of-concept” clinical trial on the topic.

The trial is being conducted by The University of Sydney School of Medicine and Parkinson’s South Australia. There is also a website where you can follow the various activities surrounding the trial – Click here to see the website.

Designing the helmet for the Sydney clinical trials. Source: ABC

And there is already published research coming out of the clinical study:

Title: “Buckets”: Early Observations on the Use of Red and Infrared Light Helmets in Parkinson’s Disease Patients.
Authors: Hamilton CL, El Khoury H, Hamilton D, Nicklason F, Mitrofanis J.
Journal: Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):615-622.
PMID: 31536464

Now to be clear, I do fully not understand the biology behind the idea, and it would be easy for me to make fun of this whole situation. But I really do love this story. The ivory towers of industry and academic research may scoff at such a story, but I hope that this study will lead to something new and wonderful (the way Joy Milne’s “smell of Parkinson’s” has opened new areas of research – click here to read a previous SoPD post about that).

The light bucket “photobiomodulation” clinical trial for Parkinson’s is a great story about the DIY attitude, community sharing/helping, curiosity & some serious left field thinking ( to read a prominent newspaper story about this).

Photobiomodulation? Are you serious? How on Earth can LIGHT help with Parkinson’s?

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The Neuraly trial

 

 

 

This week a new clinical trial was registered which caught our attention here at the SoPD HQ. It is being sponsored by a small biotech called Neuraly and involves a drug called NLY01.

NLY01 is a GLP-1R agonist – that is a molecule that binds to the Glucagon-like peptide-1 receptor and activates it. Other GLP-1R agonists include Exenatide (also called Bydureon) which is also also about to start a Phase III clinical trial in Parkinson’s (Click here to read a previous SoPD post about this).

There is a lot of activity in the Parkinson’s research world on GLP-1R agonists at the moment.

In today’s post, we will discuss what a GLP-1R agonist is, what we know about NLY01, and what the new clinical trial involves.

 


 

Every week there are new clinical studies being announced for Parkinson’s.

Many of them are registered on the Clinicaltrials.gov website. Here at the SoPD, we try to keep track of new trials being registered (the SoPD Twitter account highlights the more interesting trials).

This week one particular newly registered clinical trial stood out. It involves a small biotech company Neuraly (which is owned by parent company D&D PharmaTech).

And the drug being tested in the Neuraly clinical trial is a GLP-1R agonist.

What is a GLP-1R agonist?

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Say it with me: Farn-e-syl-trans-fer-ase

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Not a week goes by without some new peice of research suggesting yet another biological mechanism that could be useful in slowing or stopping Parkinson’s. This week researchers in Chicago reported that pharmacologically inhibiting a specific enzyme – farnesyltransferase – may represent a novel means of boosting waste disposal and helping stressed cells to survive.

A number of farnesyltransferase inhibitors are being developed for cancer, and there is the possibility of repurposing some of them for Parkinson’s.

In today’s post, we will discuss what farnesyltransferase is and does, what the new research report found, and we will consider whether inhibition of this biological pathway is do-able for Parkinson’s.

 


Source: Knowledgepathinc

I am in the midst of preparing the “end of year review” and “road ahead” posts for 2019/2020 (they take a while to pull together). But it is already extremely apparent that we have an incredible amount of preclinical data piling up,…. and a serious bottleneck at the transition to clinical testing.

It is actually rather disturbing.

Previously this was a concern, but going forward – as more and more novel preclinical work continues to pile up – one can foresee that it is going to be a serious problem.

But there is just SOOOO much preclinical data on Parkinson’s coming out at the moment. Every single week, there is a new method/molecular pathway proposed for attacking the condition.

A good example of this frenetic pace of preclinical research is a recent report from researchers in Chicago, who discovered that a farnesyltransferase inhibitor could be beneficial in Parkinson’s.

Farne…syl… what?

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An exercise in expectations: Exenatide III

 

In August 2017, the results of a Phase II double-blind, placebo controlled clinical trial investigating whether the diabetes drug Exenatide (aka Bydureon) can be repurposed for the treatment of Parkinson’s were published.

Despite the fact that the study did not meet most of its end points, the Parkinson’s community got very excited about one of the results: The exenatide treated group demonstrated a stabilisation of their motor features over the 48 week trial, while the control group continued to worsen.

Over night, for many in the community, the hypothetical (a “disease-halting medication”) suddenly become a possibility. After such a long trail of negative clinical trial results, it was a very human and natural response for everyone to get excited. But with the news this month, that the Phase III exenatide clinical trial is about to start, the community needs to curb that excitement in order for a proper evaluation of the drug to take place.

In today’s post, we will look at the details of the new Phase III clinical trial for Exenatide and discuss why it is important to manage expections.

 


 

Here on the SoPD website we are often discussing novel potentially disease modifying therapies for Parkinson’s. And it is rather staggering the number and range of different approaches currently being tested on Parkinson’s.

And I am often asked, “Simon, if you were a betting man, which one I would put my money on? Which one are you expecting to work?

Now, before we go on dear reader, please understand that my answer to this question will problably disappoint you.

You see, I do not expect any of these experimental treatments being clinically tested to work.

WHAT THE?!?

Now, before you turn off, please let me explain – because this is important (it is not click-bait).

Ok, I’m listening. Why don’t you expect any of these treatments to work?!?

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Administrative news: One year #PostAc

 

Today’s post will be something a little different: 12 months ago today I stepped away from being a Parkinson’s research scientist and joined the Cure Parkinson’s Trust in a new role of deputy director of Research.

It has been an amazing (and very busy – note the back dating of this post!) year! I definitely have no regrets, and the honeymoon is certainly not over – I am still very much loving the new role and the challenges/opportunities it brings.

There have been some major adjustments though and a few unexpected surprises.

In today’s post, I will discuss what I have learnt over the last 12 months and share some of my observations.

 


 

 

As regular readers will know, after 15 years of both lab- and clinic-based Parkinson’s research, last year on the 1st October I stepped away from the academic world to take on a new role as the Deputy Director of Research at the Cure Parkinson’s Trust.

It was a rather crazy moment for me personally, because at the same time that I was being offered this deputy director job, I was also being offered a lecturer position at a UK university.

A university lecturer. Source: Salford

Now, understand dear reader that I had been gunning for a lecturer position for the last 5 years – completing dozens of applications and only being invited to a handful of interviews. It had been a long hard slog, but having my own research group had been the goal for a long time. I was so focused on that idea, that I had not really entertained any other options.

So it was somewhat bewildering when a group like the Cure Parkinson’s Trust came out of left field and offered me something completely different.

And it was truly one of the more surreal moments of my life to then actually say ‘Sorry, but no thanks‘ to the one thing that I had been striving for for so long, and to say ‘Yes please!‘ to this fascinating second option.

But the decision to join the Trust was very easy in the end.

What do you mean?

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Monthly Research Review – September 2019

 

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 September 2019.

The post is divided into seven parts based on the type of research:

  • Basic biology
  • Disease mechanism
  • Clinical research
  • New clinical trials
  • Clinical trial news
  • Other news
  • Review articles/videos

 


So, what happened during September 2019?

In world news:

11th September – Astronomers announced the detection of water in the atmosphere of an exoplanet called K2-18b – the first such discovery for an exoplanet in the habitable zone around a star (Click here to read more about this).

17th September – Josh Thompson from New Zealand was going to be made redundant, so he hired a clown to take to his redundancy meeting as his ‘support person’ (as is provided by NZ law). Joe the clown made sad faces when the conversation went negative and also made balloon animals throughout the meeting (only in NZ! – Click here to read more about this):

20th September – The Rugby World Cup started in Japan… and we all know who’s going to win (famous last words!)

28th September – SpaceX presented the Mark1 – the first prototype of their ‘Starship’ which is being developed for interplanetary travel.

 

And it was with sadness that the Parkinson’s research community heard about the passing of Prof Sir Chris Dobson. Most readers will not be aware of his incredible contributions to the field of Parkinson’s and neurodegeneration in general – he will be missed (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 September 2019, there were 831 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6215 for all of 2019 so far, and compared to 5978 at the same time in 2018). 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

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A.S.A.P

 

 

 

Yesterday the Aligning Science Across Parkinson’s (ASAP) initiative published a point of view in the scientific journal eLife. It laid out the objectives, themes and philosophy of an enormous new scientific effort to better understand Parkinson’s.

The overall project is being led by a Nobel prize winner scientist and employing the considerable resources of a very wealthy family that has been affected by Parkinson’s.

In today’s post we will have a look at what the ASAP initiative is planning to do and how it will hopefully significantly enhance our understanding of Parkinson’s.

 


Google co-founder Sergey Brin. Source: Emaze

Every so often something comes along that is so ‘next level’ in its scale and ambition that it gives you pause.

Two years ago, key Parkinson’s researchers from around the world were invited to the Milken Institute Center in for a grand meeting that was organised to plan out the foundations of a major new Parkinson’s research program that was to be called Aligning Science Across Parkinson’s (or ASAP).

The event was organised by Google co-founder Sergey Brin and his family foundation. The Brin family have been affected by Parkinson’s (Sergey’s mother and aunt both have the condition, and Sergey has a genetic risk factor that increases his risk of developing Parkinson’s).

The Brin Family – Sergey and his mother on the right. Source: CS

Sergey and his mother both carry a genetic variation in a region of DNA called PARK8. It is also known as Leucine-rich repeat kinase 2 (or simply LRRK2 – pronounced ‘lark 2’). The variant increases the risk of developing an young-onset, slow progressing form of Parkinson’s (Click here to read more about LRRK2). Sergey may never develop the condition, but he has decided not to take any chances. He has taken out an “insurance policy” by investing hundreds of millions of dollars into Parkinson’s research.

Part of that insurance policy is the ASAP effort.

And ASAP is being coordinated by Prof Randy Schekman.

Who is Prof Randy Schekman?
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A new reason to hate mosquitos?

 

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.

photo_66943_landscape_650x433

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?

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Repurposing: From enlarged prostates to Parkinson’s

 

This week exciting new research from a collaboration between Chinese researchers and scientists at the University of Iowa has pointed towards a clinically-available, generic drug that could be re-purposed for Parkinson’s.

The researchers found a drug called Terazosin – which is used for the treatment of enlarged prostates and high blood pressure – can boost energy production in neurons, and also rescue multiple preclinical models of Parkinson’s (including human cell cultures).

Most intriguing, however, was their discovery that people taking Terazosin (or similar drugs) have a reduced incidence of Parkinson’s, and people with Parkinson’s who take Terazosin seem to have less disease progression.

In today’s post, we will look at what Terazosin is, how it functions, what this new research suggests, and how the finding is being taken forward.

 


Reader questions. Source: Yoursalesplaybook

So I have had a few inquiries over the last 24 hours.

Lots of questions.

A wee bit of interest in some recent Parkinson’s associated research.

It seems that there was a bit of excitement generated by press releases regarding new research from a group of researchers in China and the University of Iowa suggesting that a commonly used blood pressure and prostate treatment called Terazosin not only had beneficial effects in multiple models of Parkinson’s, but also reduced the incidence of Parkinson’s in people taking the drug.

Terazosin. Source: Wikipedia

Here is the study in question:

Title: Enhancing glycolysis attenuates Parkinson’s disease progression in models and clinical databases.
Authors: Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L.
Journal: J Clin Invest. 2019 Sep 16. pii: 129987.
PMID: 31524631                (This report is OPEN ACCESS if you would like to read it)

In this study, the researchers investigated the properties of a drug called terazosin in various models of Parkinson’s.

What is terazosin?

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Resolvin(g) Parkinson’s

 

A major focus on Parkinson’s research is inflammation.

Inflammation is a vital part of our immune system’s response to infection or injury. It is means by which the body signals to the cells of immune system that something might be wrong and help is required. It is a complex, multi-stage process, involving many different mechanisms which help to amplify and resolve the response.

Recently, some researchers reported some interesting data regarding the ‘resolving’ aspect of the inflammatory response in Parkinson’s. It involved a protein called Resolvin.

In today’s post, we will look at what Resolvin is, what the new research reported, and how this information could be useful in the development of future therapies for Parkinson’s.

 


Spot the unhealthy cell – exhibiting signs of stress (yellow). Source: Gettyimages

When cells in your body are stressed or sick, they begin to release tiny messenger proteins which inform the rest of your body that something is wrong.

When enough of these messenger proteins are released that the immune system becomes activated, it can cause inflammation.

What is inflammation?

Inflammation is a critical part of the immune system’s response to trouble. It is the body’s way of communicating to the immune system that something is wrong and activating it so that it can help deal with the situation.

By releasing the messenger proteins (called cytokines), injured/sick cells kick off a process that results in multiple types of immune cells entering the troubled area of the body and undertaking very specific tasks.

The inflammatory process. Source: Trainingcor

The strength of the immune response depends on the volume of the signal arising from those released messenger proteins. And there are processes that can amplify the immune response.

But an important component of the immune response that is often overlooked is resolution.

Once an infection/injury has been dealt with, the immune response must be resolved. And there are tiny messenger proteins that our body producing naturally which involved in dampening down the immune response. They are typically released when a situation has been resolved.

One group of resolving messenger proteins are called Resolvins.

What are Resolvins?

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