Category: Uncategorized

The Wim Hof method

 

A regular theme of the SoPD website is the reviewing of novel phamarcological treatments that are being tested on models of Parkinson’s. And while the breadth of the research is exciting and encouraging, the average reader may feel distant to the results of those studies as the experimental drug being tested is still a long way from possible regulatory approval.

There have been numerous requests to explore more readily applicable research, which could be useful for the Parkinson’s community to explore (for example, diet and exercise). This is dangerous ground for a blogger to tread on, but in the interest of stimulating discussion (and possibly research), we shall do our best.

In today’s post, we will discuss what the Wim Hof method is, what research supports it, and potential issues with applying it to conditions like Parkinson’s.

Before we start: This post is not an endorsement of the Wim Hof method, but rather an exploration of the research that has been conducted on it. The author has had no contact with Mr Hof or any associated parties, nor is he aware of any clinical research investigating the Wim Hof method in the context of Parkinson’s. The author is simply fulfilling a request to discuss the topic.

 


Source: PDUK

I am regularly asked to give an opinion (or write a blog post) about a method or technique that is being advertised online as a remedy for all aliments (including Parkinson’s).

What do you think of the ________ method?” folks will ask.

Many of these techniques I am unaware of and I can simply give a polite “I honestly don’t know” kind-of response. But for others, where I do have a little information I find myself rather conflicted.

Why conflicted?

A lot of these online methods/techniques involve commercially-focused entities hidden behind a veneer of testimonials, and very few of them have any actual real science backing them. It is difficult for anyone to give an opinion, let alone write a post about it.

But if people in the Parkinson’s community are experiencing some kind of benefits from a particular method, who am I to say otherwise or pour doubt on their experience given the lack of alternatives (I do draw a line, however, at dodgy stem cell clinics – they are all charlatans).

Source: The conversation

But recently a friend within the PD community asked me to look into the “Wim Hof method”. And while I reluctantly agreed to, I have to say that I was pleasantly surprised

Why surprised?

Because there was actual real research backing up some of the claims! The method has never been clinically tested on Parkinson’s (as far as I’m aware), but researchers have had a look at the method and the results are worth discussing.

What is the Wim Hof method?

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A plutocratic proposal: iCancer

  

Speeding up the clinical development process is a shared goal across many medical conditions (not just Parkinson’s and neurodegeneration), and there are many different approaches to achieving this that are being explored.

Some of these approaches could be considered to be bordering on the unethical, but there are aspects of their structure and design that are still worthy of academic discussion and consideration.

One example is a crowd-funded cancer clinical trial called iCancer.

In today’s post, we will discuss the iCancer project.

 


Source: Entitymag

Over the Christmas period, in addition to spending the required amount of time with family and friends, I fell down a rabbit hole.

Before the festive season, I had been exploring different designs of clinical trials to see what had been given serious academic consideration and thought.

I was particularly intrigued with the ‘pay-to-play’ model (in which patients pay to be part of a study). This model has fallen into disgrace due to abuse by unscrupulous individuals profiting off untested, experimental therapies being targeted towards desperate patients.

To be clear: it is utterly unethical for “for-profit” clinics to be selling access to experimental procedures if there is no proof of efficacy (and this is particularly true for the stem cell clinics).

Source: FDA

But I was interested in exploring if anyone had actually explored this type of clinical study design or aspects of it in the academic sense as a means of speeding things up.

In my role as a research co-ordinator for a Parkinson’s charity, I have been lucky enough to meet and get to know some folks who are absolute fountains of knowledge and wisdom when it comes to all things related to clinical trial design. And I just straight up asked some of these individuals if anyone had ever given serious academic thought to the ‘pay-to-play’ model?

I recieved an interesting collection of answers – all erring on the side of extreme caution, with some taking a “are you %#@&£$ serious” tone – and I suspect that any reputation I might have had with those individuals is now dented (such is the taint of pay-to-play).

But one individual – perhaps in an effort to reorient a foolish, but hungry mind – pointed me towards a possibly better approach.

It is being proposed by a group called iCancer.

What is iCancer?

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Monthly Research Review: Jaunary 2020

 

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 January 2020.

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, and Review articles/videos

 


So, what happened during January 2020?

In world news:

January 6th – From the only in London files – this was “No Trousers Tube Ride 2020” day (don’t ask me to explain… I wouldn’t know where to begin – click here to read more about this).

January 23rd – The Chinese city of Wuhan was placed under quarantine, in which all public transport in and out of the city was suspended in efforts to control the spread of a new coronavirus, designated 2019-nCoV.

January 26th – In the build up to BREXIT, the UK presented the new 50 pence coin… with a gramatical error. Three million coins bearing the slogan “Peace, prosperity and friendship with all nations” are due to enter circulation from 31 January (Click here to read more about this).

January 30th – The Daniel K Inouye Solar Telescope on Hawaii released new footage of the surface of the sun showing features as small as 30km across.(Click here to read more about this).

 

31st January – As the bush fires in Australia have continued over January, a state of emergency was declared in the Canberra region, with fires reaching suburbs just south of the capital (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 January 2020, there were 849 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (8195 for all of 2019 – updated number). 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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Natural (born) killers

 

Today’s post starts with more of a biology lesson than usual, but it is important to understand where in the grand scheme of things a certain type of blood cell sits.

That type of blood cell has a really cool name: Natural killer cells.

Recently researchers at the University of Georgia (USA) published a report suggesting that natural killer cells may be a key player in the immune system response to Parkinson’s.

Specifically, they found that natural killer cell numbers are higher in disease-affected parts of the Parkinsonian brain, and that natural killer cells digest free floating alpha synuclein aggregates.

In today’s post, we will discuss what natural killer cells are, review this new research report, and explore what this new finding could mean for Parkinson’s.

 


Milestone! Source: Smilingkidsindy

My daughter recently lost her first tooth, and there was a bit of blood. We patched her up, but also took advantage of the moment to learn a little something about how the body works.

Me: Do you know what that red stuff is?

Little monster: Is it blood?

Me: That’s right.

Little monster: Am I going to die? (accompanied with a sudden and very concerned look on her face)

Me: No.

Extremely relieved little monster: Papa, where does blood come from?

And that was when I got all excited, and pulled out my black board.

Admittedly it took a while, but this was the answer I gave her:

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Probiotics: Food for worms?

 

 

There is a lot of research currently being conducted that is exploring the relationship between the gastrointestinal system and Parkinson’s. A growing body of data suggests that the bacteria in our guts may be having an infuential role.

Recently researchers at the University of Edinburgh in Scotland have published the results of a study in which they used microscopic roundworms to explore bacteria that can influence the pathology associated with Parkinson’s.

And they announced that the bacteria that they had identified is present in many available probiotics.

In today’s post, we will look at what roundworms are, what is meant by probiotic, and what this new research found.

 


Not the PDUK committee. Source: Eagle

What I am about to do is utterly inappropriate, but it will hopefully provide readers with a small insight into what is happening behind the scenes in Parkinson’s research.

Several years ago I was a member of the Parkinson’s UK project grant review panel, and our job was to review applications from fellow researchers who were requesting funds to conduct large and ambitious projects. Following several weeks of reviewing the grants, we had all travelled down to London to discuss a set of applications that had been shortlisted for funding. About 30 people (both academics and PwPs) were in the room, sitting around a large square of tables, and it was our job to select the grants that should be funded.

There was a lot of pros and cons being discussed for each application… and then we came to one particular grant that I think had caught everyones eye.

It involved using C. elegans to screen for gut bacteria that may influence aspects of Parkinson’s biology.

What are C. elegans?

Caenorhabditis elegans (or simply C. elegans) are transparent nematode – also known as roundworms. They are about 1 mm in length, and they have very well characterised nervous systems (useless pub quiz fact: C. elegans have 302 neurons and 56 glial cells in total, which communicate through approximately 6400 chemical synapses, 900 gap junctions, and 1500 neuromuscular junctions – like I said, well characterised!).

Caenorhabditis elegans – cute huh? Source: Nematode

Given their well characterised nervous systems, C. elegans provide a useful tool for studying biology. They are easy to grow/maintain, they have an overall life span of 2-3 weeks, and researchers have developed a wide range of tools that allow for genetic manipulation to address specific questions.

But the idea of using these little guys to study the bacteria of the gut was such a novel idea. The grant funding panel sat there wondering if these creatures even had bacteria in their guts (they do – click here to read a review of the first 3 studies on this topic, all published in 2016).

I liked the novelty of the approach and thought that the high-throughput nature of the study would provide quick answers (a lot of bacteria could get studied very quickly using C. Elegans, compared to other organisms like mice).

But there was a lot of debate about this application, centred mainly around the idea of “How will any of this translate to humans?

Source: DMM

Eventually I think curiosity won the day and the committee agree that the application should be funded. And I’m glad it was, because very recently the first results of the study have been published,… and they are really interesting.

What did the study find?

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Not dead, dormant dopamine neurons?!?

 

Every textbook written about the condition will tell you that the classical pathological characteristic of Parkinson’s is the loss of dopamine neurons in the midbrain region of the brain. It is the distinguishing feature that pathologists look for in order to provide a postmortem diagnosis of the condition.

But what is meant by the words ‘loss of dopamine neurons’? Do the cells actually die? Recently researchers from Korea have published new data exploring this question.

Interestingly, they found evidence of ‘dormant’ dopamine neurons in postmortem sections of brains from people with Parkinson’s – even those with severe forms of the condition.

In today’s post, we will discuss what a dopamine neuron is, what this new research found, and what it could mean for our understanding of Parkinson’s.

 


Source: Bettys

2019 represented the centenary year for an important discovery in Parkinson’s research.

In 1919, the Uzbek neuropathologist Konstantin Tretiakoff (1892-1958) reported his findings regarding an examination of 54 human brains.

Konstantin Tretiakoff. Source: Wikipedia

Six of the postmortem brains had belonged to individuals who had suffered from Parkinson’s and three others had been diagnosed with postencephalitic Parkinsonism. In these brains he noticed something rather striking.

What did he find?

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The Ambroxol Results

 

The new year has started with some pleasing clinical trial news for the Parkinson’s community: The results of the “Ambroxol in Disease Modification in Parkinson Disease” (AiM-PD study) have been published.

This is a clinically available drug that is used for the treatment of respiratory issues, which researchers are re-purposing for Parkinson’s based on some interesting properties the drug has.

The results of the clinical trial suggest that ambroxol was safe and well tolerated in people with Parkinson’s for the length of the 6 month study. It accessed the brain and increased levels of target proteins while there.

In today’s post, we will discuss what ambroxol is, what research has been conducted on it, and what the results of this study suggest.

 


The author of this blog is the deputy director of research at The Cure Parkinson’s Trust, and as such he feels that it is necessary to start this post with a very clear declaration –  FULL DISCLOSURE: The Cure Parkinson’s Trust (in partnership with the Van Andel Institute) was a funder of the ambroxol clinical trial which is going to be discussed in this post.

Right. That said, let’s try and do a completely unbiased review of the ambroxol trial results 🙂

In one particular SoPD post last year we discussed the Linked Clinical Trials initiative, which is an international program that was set up 8 years ago with the goal of rapidly repurposing clinically available drugs exhibiting disease modifying potential in models of Parkinson’s (Click here to read the previous SoPD post on this topic).

What is meant by repurposing?

Drug repurposing (repositioning, reprofiling or re-tasking) is a strategy of identifying novel uses for clinically approved drugs that fall outside the scope of the original medical indication.

An example of this is “Viagra”.

It was originally developed as an anti-hypertensive medication, but was hugely more successful in the treatment of erectile dysfunction.

The strategy has been adopted and applied by many organisations because it allows for the by-passing of large parts of the drug discovery process, saving time and resources in getting new treatments to the clinic.

Source: Austinpublishinggroup

By repurposing a clinically approved drug – for which we may know a great deal about already in terms of safety, tolerability and dose range – we can skip large parts of the clinical trial process and jump straight to testing the drug in our population of interest (in this case people with Parkinson’s).

And this is what the Linked Clinical Trials (or LCT) program was set up to do in Parkinson’s.

The first drug that was prioritised by the LCT committee for repurposing was a diabetes drug called exenatide (also known as Bydureon).

It is fair to say this LCT-initiated clinical trial program has provided interesting results thus far (Click here and here to read a SoPD post on this) and the exenatide program is now entering Phase III testing in Parkinson’s (Click here to read more about the Phase III trial).

In late 2014, the LCT committee prioritised another clinically available drug for repurposing to Parkinson’s.

That drug is called ambroxol.

What is ambroxol?

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2020 wish list

 

Here at the Science of Parkinson’s, we don’t like making predictions – that’s a mug’s game.

We would rather explore interesting ideas based around what we hope to see happen in 2020 – discussing different ways and means by which they could occur – in the hope that some one will pick up the ball and run with it (ideally, they already have the ball and we are as usual naively unaware).

In today’s post, we will outline the SoPD wish list for 2020.

 


Source: Amazon

In his excellent biography on Leonado Da Vinci, author Walter Isaacson drops a beautiful hook in the middle of the book to compel the reader on.

As you may be aware, Da Vinci kept lots of journals throughout his life, and he was constantly making drawings and notes. On almost every page, however, he also made list of things to do, and these list suggest an incredibly curious mind.

Isaacson listed a few examples, including:

“Get the master of arithmetic to show you how to square a triangle… Ask Giannino the Bombardier about how the tower of Ferrara is walled… Ask Benedetto Protinari by what means they walk on ice in Flanders… Get a master of hydraulics to tell you how to repair a lock, canal and mill in the Lombard manner…”

Source: Kottke

But in the middle of the book, Isaacson gives the reader his personal favourite:

“Describe the tongue of the woodpecker”

And then he continues:

“‘Describe the tongue of the woodpecker,’ he instructs himself. Who on earth would decide one day, for no apparent reason, that he wanted to know what the tongue of a woodpecker looks like? How would you even find out? It’s not information Leonardo needed to paint a picture or even to understand the flight of birds”

Wait. What? Woodpeckers have tongues?!?

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The road ahead: 2020

Here at the SoPD, we are primarily interested in disease modification for Parkinson’s. While there is a great deal of interesting research exploring the causes of the condition, novel symptomatic therapies, and other aspects of Parkinson’s, my focus is generally on the science seeking to slow, stop or reverse the condition.

At the start of each year, it is a useful practise to layout what is planned and what we will be looking for over the next 12 months. Obviously, where 2020 will actually end is unpredictable, but an outline of what is scheduled over the next year will hopefully provide us with a useful resource for better managing expectations.

In this post, I will try to lay out some of what 2020 holds for us with regards to clinical research focused on disease modification for Parkinson’s.


BP

Lord Robert Baden-Powell. Source: Utahscouts

My old scout master once looked around our horse shoe, making eye contact with each of us, before asking the question:

“When did Noah build the ark?”

My fellow scouts and I looked at each other – confused. Did he want an exact date?!?

The scout master waited a moment for one of us to offer up some idiotic attempt at an answer – thankfully no one did – before he solemnly said:

“Before the rain”

It was one of those childhood moments that made little sense at the time, but comes back to haunt you as an adult when you are looking at what the future may hold and trying to plan for it.

# # # # # # # # # # #

Today’s post is our annual horizon scanning effort, where we lay out what is on the cards for the next 12 months with regards to clinical research focused on disease modification in Parkinson’s.

Source: Rand

We will also briefly mention other bits and pieces of preclinical work that we are keeping an eye on for any news of development.

To be clear, this post is NOT intended to be an exercise in the reading of tea leaves – no predictions will be made here. Nor is this a definitive or exhaustive guide of what the next year holds for disease modification research (if you see anything important that I have missed – please contact me). And it should certainly not be assumed that any of the treatments mentioned below are going to be silver bullets or magical elixirs that are going to “cure” the condition.

In the introduction to last year’s outlook, I wrote of the dangers of having expectations (Click here to read that post). I am not going to repeat that intro here, but that the same message applies as we look ahead to what 2020 holds.

Source: Unitystone

In fact, it probably applies even more for 2020, than it did for 2019.

2020 is going to be a busy year for Parkinson’s research, and I am genuinely concerned that posts like this are only going to raise expectations. My hope is that a better understanding of where things currently are and what is scheduled for the next 12 months will help in better managing those expectations. Please understand that there is still a long way to go for all of these experimental therapies.

All of that said, let’s begin:

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2019: Year in review

 

In this end-of-year post, we review the Parkinson’s research that caught our attention at SoPD HQ in 2019.

Month-by-month we will briefly discuss some of the major pieces of research/announcements that have defined the year and advanced our understanding of Parkinson’s. The list is based on nothing more than the author’s personal opinion – apologies to any researchers who feel left out – and the contents should certainly not be considered definitive or exhaustive.

It was just some of the stuff that made me say “wow” in 2019.

And in the next post, we will conduct our annual horizon scan and consider what 2020 may have in store for us.

 


Source: a-star

2019 was a productive year for the Parkinson’s research community.

Wait a minute. Hold your horses. What is that statement based on?

If we use number of research report published in 2019 as our measure, there was a total of 8094 articles added to the Pubmed website with the tag word “Parkinson’s” attached (compared to 7672 for all of 2018 and 7675 for 2017). That sounds rather productive.

In addition, there were a host of new clinical trials initiatiated, many of which are exploring entirely new experimental therapies. These include:

  • UDCA (aka Ursodeoxycholic acid) – A bial acid therapy used for reducing gall stones that may improve mitochondrial function entered Phase II testing for Parkinson’s (Click here to read a SoPD post on the topic).
  • PR001 – A gene therapy targetting GBA-associated Parkinson’s (Click here to read a SoPD post about this).
  • CNM-Au8 – Gold nanoparticles entered Phase II testing for Parkinson’s (Click here to read an SoPD post about this research).
  • Terazosin – This prostatic hyperplasia and hypertension drug was found to enhance Phosphoglycerate kinase 1 (Pgk1) activation & a Phase II trial was immediately initiatiated (Click here to read an SoPD post on this topic).
  • Inzomelid – An NLRP3 inhibitor from Inflazome began Phase I testing (Click here to read a SoPD post on this topic).

On top of all of this, numerous novel potenially therapeutic pathways were proposed, such as:

  • Farnesyltransferase inhibition (Click here to read a SoPD post on the topic)
  • Miro1 degradation (Click here to read an SoPD post on the topic).
  • CD22 inhibition (Click here to read a SoPD post on this topic).
  • Felodipine – Researchers discovered that this L-type calcium channel blocker & anti-hypertensive drug boosts waste disposal (or autophagy) in mouse brains (Click here to read an SoPD post on the topic).

Plus, there were a number of major Parkinson’s research organisations launched, including the Australian Parkinson’s Mission (Click here to read more about this), Aligning Science Across Parkinson’s (ASAP – click here to read more about this), the Accelerating Medicines Partnership for Parkinson’s disease (or AMP-PD) initiative (Click here to read more about this), and the Chan Zuckerberg Initiative.

Based on all of this, I think it is safe to say that 2019 was a productive year for Parkinson’s research.

Ok, all of that sounds great, but what does that mean for someone living with the condition?

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