Parkinson’s: When evolution leaves parts of us behind?

 

Recently researchers have proposed an interesting idea for why Parkinson’s is a distinctly human condition: There are parts of our brains that have not kept up with evolution, and as we live longer those areas become strained which ultimately results in the features of Parkinson’s.

It’s a really interesting idea – one which could have major implications.

In today’s post, we will review the new proposal and consider how we could use it in our approach to therapeutic interventions.

 

2020 Tesla Roadster. Source: Motortrend

By nature and design, I am not a car person.

If I can actually fit in the car (I am rather tall) and it gets me from A to B, it’s a great car. I don’t really care what it looks like, because I usually look ridiculous in the more sporty versions (my knees up around my ears…). As long as it gets from A to B, I’m happy.

Having said that, I do appreciate the technological advancements that are being made by companies like Tesla (I mean seriously, their Roadster – pictured above – is an electric car that does 0-60 mph in 1.9-seconds, quarter-mile in less than 9-second, a 250-plus-mph top speed, and an all-electric range of 620-mile! All of those statistics are incredible!).

It is amazing the evolutionary process that automobiles have gone through.

The first petrol engine-propelled car invented by Karl Benz. Source: Oxfordsurfaces

Every aspect of these vehicles has changed over time. From the wheels to the engine and from petrol to electric based cars, each component has been adapted across the decades to keep up with the needs of its environment.

Researchers are now wondering if the same can be said for our brains. And just recently some scientists have questioned whether some evolutionary design faults could explain why humans develop Parkinson’s.

What?!? What do you mean?

Continue reading →

Bac to the future


Over the last few years, there has been a growing body of research – and tremendous interest – focused on the role/influence of the gastrointestinal system in Parkinson’s.

In today’s post we are going to look at a recent piece of research that suggests some of the bacteria in our gut can influence the availability of the medication we use to treat Parkinson’s. 

In addition, we will look at a novel way researchers are re-engineering bacteria in the gut to correct other medical conditions (such as phenylketonuria) and we will ask if the same can not be applied to Parkinson’s.

 

The Platypus. Source: National geographic

The interesting, but utterly useless fact of the day: The duck-billed Platypus of Australia does not have a stomach.

What?

No really. These oddities of evolution have no stomach. There’s no sac in the middle of their bodies that secrete powerful acids and digestive enzymes. The oesophagus (the tube from the mouth) of the platypus connects directly to its intestines.

The platypus. Source: Topimage

And believe it or not, platypus are not alone on this ‘sans estomac‘ trend. At least a 1/4 of the fish species on this planet do not have a stomach (Source).

What?!?

And this absense of the stomach isn’t even remotely weird in the animal kingdom. Some creatures don’t even have a gastrointestinal system. No mouth. No anus. No intestines. Nothing.

WHAT?!?

The giant tube worm – Riftia pachyptila – lives on the floor of the Pacific Ocean, next to hot hydrothermal vents and can tolerate extremely high levels of hydrogen sulfide (hazardous for you and I). These creatures – which can grow up to 2.4 meters (or 7+ feet) in length – have no gastrointestinal tract whatsoever. Zip, zero, nada.

Rather they have an internal cavity – called a trophosome – filled with bacteria which live symbiotically with them.

Watch this video of Ed Yong explaining it all (great video!):

WOW! Fascinating! But what does ANY of this have to do with Parkinson’s?

Continue reading →

The UP Study – UDCA in Parkinson’s

 

Today we received word of a new clinical trial for Parkinson’s being initiated here in the UK. This trial – named the UP study – will evaluate the safety and tolerability of a compound called Ursodeoxycholic acid (or UDCA – click here to read the press release).

UDCA is clinically available medication that is used in the treatment of gall stone, but recently there has been a large body of research suggesting that this compound may also have beneficial effects in Parkinson’s.

In today’s post, we will look at what UDCA is, discuss the preclinical research exploring UDCA, and outline the structure of the new clinical trial.

 

Source: Youtube

How often do you consider your gallbladder?

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).

Source: Mayoclinic

One of the down sides of having a gall bladder: gallstones.

Gallstones are hardened deposits that can form in your gallbladder. About 80% of gallstones are made of cholesterol. The remaining 20% of gallstones are 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 or a new clinical trial?

One of the treatments for gallstones is called UDCA. And today we found out that this compound is being clinically tested for “repurposing” as a treatment for Parkinson’s.

What is UDCA?

Continue reading →

On your MARCKS. Get set. Go

 

An important aspect of developing better remedies for Parkinson’s involves determining when and where the condition starts in the brain. What is the underlying mechanism that kicks things off and can it be therapeutically targetted?

Recently, researchers from Japan have suggested that a protein called Myristoylated alanine-rich C-kinase substrate (or simply MARCKS) may be a potentially important player in the very early stages of Parkinson’s (and other neurodegenerative conditions).

Specifically, they have found that MARCKS is present before many of the other pathological hallmarks of Parkinson’s (such as Lewy bodies) even appear. But what does this mean? And what can we do with this information?

In today’s post, we will look at what MARCKS is, what new research suggests, and how the research community are attempting to target this protein.

 

Where does it all begin? Source: Cafi

One of the most interesting people I met during my time doing Parkinson’s assessment clinics was an ex-fire forensic investigator.

We would generally start each PD assessment session with a “brief history” of life and employment – it is a nice ice breaker to the appointment, helped to relax the individual by focusing on a familiar topic, and it could provide an indication of potential issues to consider in the context of Parkinson’s – such as job related stress or exposure to other potential risk factors (eg. pesticides, etc).

Source: Assessment

But so fascinated was I with the past emplyoment of the ex-fire forensic investigator gentleman that the “brief history” was anything but brief.

We had a long conversation.

One aspect of fire forensics that particularly fascinated me was the way he could walk into a recently burned down property, and he could “read the story backwards” to identify the root cause of the fire.

He could start anywhere on a burnt out property and find his way back to the source (and also determine if the fire was accidental or deliberate).

Where did it all start? Source: Morestina

I marvelled at this idea.

And I can remember wondering “why can’t we do that with Parkinson’s?”

Well, recently some Japanese researchers have had a crack at “reading the story backwards” and they found something rather interesting.

What did they find?

Continue reading →

Monthly Research Review – January 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 January 2019.

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

  • Basic biology
  • Disease mechanism
  • Clinical research
  • New clinical trials (Oooh, new section for 2019!)
  • Clinical trial news
  • Other news
  • Review articles/videos

 

So, what happened during January 2019?

In world news:

January 1st – All works published in 1923 (except sound recordings) lost copyright and entered the public domain in the United States. You may do what you like with Sigmund Freud‘s “The Ego and the Id”, Kahlil Gibran’s “The Prophet”, and of course: “The Charleston”.

 

 

 

 

January 3 – The Chinese probe Chang’e 4 became the first human-made object to land on the far side of the Moon.

(This is actually Chang’e 3, but it’s a nice pic!)

January 11th – Researchers at the University of Michigan demonstrated a new approach to 3D printing. It is based on lasers and simply the lifting of shapes from a vat of liquid. And it is 100 times faster than conventional 3D printing processes! It is rather amazing (Click here to read the research report and click here for the press release).

 

 

 

25 January – AlphaStar, a new artificial intelligence algorithim by Alphabet’s DeepMind subsidary, defeated professional players of the real-time strategy game StarCraft II in ten rounds out of eleven (I don’t even know what StarCraft II is, but this terrifies me).

30th January – The temperature in the city of Chicago hit a daytime high of -24C (-11F ?!?!?). It then dropped to a low of -28C overnight (I repeat: ?!?!?).

In the world of Parkinson’s research, a great deal of new research and news was reported:

In January 2019, there were 694 research articles added to the Pubmed website with the tag word “Parkinson’s” attached. 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

Continue reading →

The Australian Parkinson’s Mission

 

At 9am on the 30th January, 2019, the Australian Government Federal Health Minister Greg Hunt announced the initiation of the ‘Australian Parkinson’s Mission‘ – a very massive $30 million clinical trial programme that will be focused on potentially disease modifying treatments for Parkinson’s.

This huge endeavour will being with a large multi-arm study – involving 300 hundred participants and investigating 4 drugs (compared to a single placebo). It will be a first of its kind project in the world targeting Parkinson’s.

This is a very exciting development for the Parkinson’s community!

In today’s post, we will discuss what we currently know about the Australian Parkinson’s Mission project, what we hope to see resulting from the initiative, and why this is a tremendous step forward for the international Parkinson’s community as a whole.

 

Source: Atom

Being a patriotic kiwi there is always enormous potential to make fun when writing a post about any Parkinson’s-related news coming out of Australia. New Zealand and Australia have always had a big brother/little brother kind of relationship (and just so we are clear: NZ is the big brother!).

But today is different.

It is very strange to say, but… today… I am actually very proud of you Australia.

At 9am this morning at the Garvan Institute of Medical Research in Sydney, Greg Hunt – the Federal Health Minister of the Australian Government – announced the commencement of a major clinical trial initiative (named ‘The Australian Parkinson’s Mission‘), which is going to be a very large, world-leading clinical programme focused on potentially disease modifying drugs for Parkinson’s (Click here to read the press release).

Struth mate!!! This sounds fantastic. What do we know about the study?

Continue reading →

An idea whose time has come

 

The year 2018 was the 20th anniversary of the discovery of the second genetic risk factor to be associated with Parkinson’s. In 1998, researchers reported that variations in a region of DNA called PARKIN were associated with an early onset form of the condition.

Early onset PARKIN-associated Parkinson’s, however, is rather different to other forms of the condition. For example, the PARKIN version appears to be largely isolated to the loss of dopamine neurons. In addition, it has limited involvement of the Parkinson’s-associated protein alpha synclein.

Recently, researcher and advocates have written a very thought provoking report pointing out these differences and and given the nature of this form of Parkinson’s, they have asked the question, why not conduct a cell transplantation clinical trial in people with early onset PARKIN-associated Parkinson’s?

It’s a really good question.

In today’s post, we will discuss what PARKIN is, what early onset PARKIN-associated Parkinson’s looks like, and why these researchers and advocates are on to a good idea.

 

Source: tmrwedition

This is Martin Taylor.

Husband, father, patriotic Scotsman, and die-hard Hearts supporter (the crazy fool).

In addition, Martin is a prominent Parkinson’s advocate.

Diagnosed in December 2014 with young onset Parkinson’s at age 32, Martin has chosen not to rest on his laurels, and has become a very active member of the Parkinson’s community, being involved with the very dynamic Edinburgh Parkinson’s Research Interest Group, and in 2017 he started the Facebook Parkinson’s Research Interest Group (or PRIG) which now has 2100+ members (including yours truly).

Martin is also a co-author of a very interesting article recently published in the European Journal of Neuroscience:

Title: Are PARKIN patients ideal candidates for dopaminergic cell replacement therapies?
Authors: Kunath T, Natalwala A, Chan C, Chen Y, Stecher B, Taylor M, Khan S, Muqit MMK.
Journal: Eur J Neurosci. 2018 Dec 26.
PMID: 30586214                (This report is OPEN ACCESS if you would like to read it)

Note: This article is part of a special edition tribute to Tom Isaacs (co-founder of the Cure Parkinson’s Trust), and there are a number of very interesting OPEN ACCESS articles in that issue.

In their article, the authors propose that individuals with early onset Parkinson’s that is associated a PARKIN genetic variant are the ideal candidates for cell transplantation therapy.

Interesting. Tell me more. But what is a PARKIN genetic variant?

Continue reading →

Exciting Exenatide Exosomes

 

Recent analysis of blood samples collected during the Phase II clinical trial of Exenatide in Parkinson’s has uncovered a very interesting finding that could have major implications for not only Parkinson’s, but for many different neurological conditions.

Exenatide is a treatment that helps to control glucose levels in people with diabetes. More recently, however, it has been suggested that this drug may also have beneficial effects in Parkinson’s. A collection of clinical trials in Parkinson’s are currently unway to test this idea.

The researchers who conducted a Phase II clinical trial of Exenatide in Parkinson’s have analysed ‘exosomes‘ collected from the blood of participants, and they found something rather remarkable.

In today’s post we will discuss what exosomes are, what the researchers found, and why their discovery could have major implications for all of neurological research.

 

 

Here on the SoPD website we have discussed at length the Phase II clinical trial of Exenatide in Parkinson’s (Click here, here and here to read more about this).

This week, however, researchers involved in the study reported yet another really interesting finding from the trial. And this one could have profound consequences for how we study not only Parkinson’s, but many other neurological conditions.

What did they find?

Last week this report was published:

Title: Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial.
Authors: Athauda D, Gulyani S, Karnati H, Li Y, Tweedie D, Mustapic M, Chawla S, Chowdhury K, Skene SS, Greig NH, Kapogiannis D, Foltynie T.
Journal: JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4304. [Epub ahead of print]
PMID: 30640362

In the Exenatide Phase II clinical trial, 60 people with moderate Parkinson’s were randomly assigned to receive either 2mg of Exenatide or placebo once weekly for 48 weeks followed by a 12-week washout (no treatment) period. The results suggested a stablisation of motor features over the 48 weeks of the study in the treated group (while the condition in the placebo group continued to progress).

During the study (which was conducted between June 2014 – June 2016), blood samples were collected at each assessement.

From those blood samples, serum was collected and analysed.

Remind me again, what is serum?

Continue reading →

Placebo. Nocebo. Gene-cebo?

 

In previous posts, we have discussed some of the potential benefits of knowing your genetic status with regards to Parkinson’s. For example, knowing if you have a certain genetic risk factor could make eligible for taking part in a particular clinical trial.

There may, however, also be some benefits in NOT knowing your genetic status.

New research suggests that simply learning of a genetic risk can alter one’s physiology.

In today’s post, we will review the results of this new research and discuss what it could mean for the Parkinson’s community.

 

Source: LongRoom

When I was a kid, I thought I was superman.

Then one of the adult figures in my life told me that I wasn’t.

And all of a sudden I lost my ability to fly.

Many years have gone by now, and its only recently that I’ve discovered that that person was actually wrong: I am Superman.

Source: Scarymommy

But curiously my powers of levitation have not (yet) returned…

The power of suggestion has always amazed me. Whether it is based on what others tell us, or on what we tell ourselves, it is truly wonderous the enormous impact some of the information we are given has on our lives. We seemingly get told something and quite often it is just accepted as gospel.

Source: izquotes

But as we take in that information, there can also be consequences (perceived or otherwise) resulting from that knowledge. And this can have important implications for us and how we interact with the world. In fact, some information that we absorb can affect our very physiology.

Can you give me an example?

Continue reading →

The “What would you do?” post

 

In this post, I will address a question that I get asked a lot: What would you do if you were diagnosed with Parkinson’s today?

Before we start, please understand that there is no secret magical silver bullet to be discussed in the following text. Such a thing does not exist, and anyone offering such should be treated with caution.

Rather, in this post I will spell out some ideas (or a plan of attack) of what I would consider doing if I was confronted with a diagnosis today and how I would approach the situation.

 

Source: Fifteendesign

An email I received this week:

Hi Simon,
Love the website. I think you are amazing and I love your dreamy eyes and perfect hair.
[ok, I may be exaggerating just a little bit here]
Given everything that you have read about Parkinson’s, what would you do if you were diagnosed with Parkinson’s today?
Kind regards,
John/Jane Doe

I get this kind of correspondence a lot, and you will hopefully understand that I am very reluctant to give advice on this matter, primarily for two important reasons:

  1. I am not a clinician. I am a former research scientist who worked on Parkinson’s for 15 years (and now help co-ordinate the research at the Cure Parkinson’s Trust). But I am not in a position to be giving medical/life advice.
  2. Even if I was a clinician, it would be rather unethical for me to offer any advice over the internet, not being unaware of the personal medical history/circumstances in each case.

While I understand that the question being asked in the email is a very human question to ask – particularly when one is initially faced with the daunting diagnosis of a condition like Parkinson’s – this is not an email that I like to receive.

I am by nature a person who is keen to help others, but in this particular situation I simply can’t.

Why not?

Continue reading →