Tagged: neurodegeneration

Trazodo or Trazodon’t?

“Repurposing” in medicine refers to taking drugs that are already approved for the treatment of one condition and testing them to see if they are safe and effective in treating other diseases. Given that these clinically available drugs have already been shown to be safe in humans, repurposing represents a method of rapidly acquiring new potential therapeutics for a particular condition. 

The antidepressant, Trazodone, has recently been proposed for repurposing to neurodegenerative conditions, such as Parkinson’s. 

In today’s post we will look at what Trazodone is, why it is being considered for repurposing, and we will review the results of a new primate study that suggests it may not be ideal for the task.


Opinions. Everyone has them. Source: Creativereview

I am regularly asked by readers to give an opinion on specific drugs and supplements.

And I usually cut and paste in my standard response: I can not answer these sorts of questions as I am just a research scientist not a clinician; and even if I was a clinician, it would be unethical for me to comment as I have no idea of your medical history.

In many of these cases, there simply isn’t much proof that the drug/supplement has any effect in Parkinson’s, so it is hard to provide any kind of “opinion”. But even if there was proof, I don’t like to give opinions.

Eleven out of every ten opinions are usually wrong (except in the head of the beholder) so why would my opinion be any better? And each individual is so different, why would one particular drug/supplement work the same for everyone?

In offering an answer to “my opinion” questions, I prefer to stick to the “Just the facts, ma’am” approach and I focus solely on the research evidence that we have available (Useless pub quiz fact: this catchphrase “Just the facts, ma’am” is often credited to Detective Joe Friday from the TV series Dragnet, and yet he never actually said it during any episode! – Source).

Detective Joe Friday. Source: Wikipedia

Now, having said all of that, there is one drug in particularly that is a regular topic of inquiry (literally, not a week goes by without someone asking about): an antidepressant called Trazodone.

What is Trazodone?

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When the zombies are all in your head

In your brain there are different types of cells.

Firstly there are the neurons (the prima donnas that we believe do most of the communication of information). Next there are the microglia cells, which act as the first and main line of active immune defence in the brain. There are also oligodendrocyte, that wrap protective sheets around the branches of the neurons and help them to pass signals.

And then there are astrocytes.

These are the ‘helper cells’ which maintain a comfortable environment for the neurons and aid them in their task. Recently, researchers in California reported an curious observation in the Parkinsonian brain: some astrocytes have entered an altered ‘zombie’-like state. And this might not be such a good thing.

In today’s post, we’ll review the research and discuss what it could mean – if independently replicated – for the Parkinson’s community.


Zombies. Source: wallpapersbrowse

I don’t understand the current fascination with zombies.

There are books, movies, television shows, video games. All dealing with the popular idea of dead bodies wandering the Earth terrifying people. But why the fascination? Why does this idea have such appeal to a wide portion of the populous?

I just don’t get it.

Even more of a mystery, however, is where the modern idea of the ‘zombie’ actually came from originally.

You see, no one really knows.

Huh? What do you mean?

Some people believe that the word ‘zombie’ is derived from West African languages – ndzumbi means ‘corpse’ in the Mitsogo language of Gabon, and nzambi means the ‘spirit of a dead person’ in the Kongo language. But how did a word from the African continent become embedded in our psyche?

Others associate the idea of a zombie with Haitian slaves in the 1700s who believed that dying would let them return back to lan guinée (African Guinea) in a kind of afterlife. But apparently that freedom did not apply to situations of suicide. Rather, those who took their own life would be condemned to walk the Hispaniola plantations for eternity as an undead slave. Perhaps this was the starting point for the ‘zombie’.

More recently the word ‘zonbi’ (not a typo) appeared in the Louisiana Creole and the Haitian Creole and represented a person who is killed and was then brought to life without speech or free will.

Delightful stuff for the start of a post on Parkinson’s research, huh?

But we’re going somewhere with this.

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Monthly Research Review – January 2018

Today’s (experimental) post provides something new – an overview of some of the major bits of Parkinson’s-related research that were made available in January 2018.


In January of 2018, the world was rocked by news that New Zealand had become the 11th country in the world to put a rocket into orbit (no really, I’m serious. Not kidding here – Click here to read more). Firmly cementing their place in the rankings of world superpowers. In addition, they became only the second country to have a prime minister get pregnant during their term in office (in this case just 3 months into her term in office – Click here to read more about this).

A happy New Zealand prime minister Jacinda Ardine

In major research news, NASA and NOAA announced that 2017 was the hottest year on record globally (without an El Niño), and among the top three hottest years overall (Click here for more on this), and scientists in China reported in the journal Cell that they had created the first monkey clones, named Zhong Zhong and Hua Hua (Click here for that news)

Zhong Zhong the cute little clone. Source: BBC

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‘Talking bout my resolution’

As we have previously discussed, 2017 was a fantastic year for Parkinson’s research (Click here to read that post). And as we approach the end of January, it is already apparent that 2018 is likely to be as good if not better (Click here for an overview of what to expect from 2018).

The transition into a new year brings with it a period of reflection and resolutions. At the start of each year I usually have a post that asks for readers feedback regarding how the SoPD website could be improved.

This year is going to be slightly different.

In today’s post we will discuss some of the ideas that I have in mind for 2018 – any and all reader feedback would be greatly appreciated.


The title of today’s post is a play on words. It is a salute to the song ‘My generation’ by the rock band “The Who” (click on the image above to hear the song). The song was released as a single on the 29th October 1965. It reached No. 2 in the UK and No. 74 in America.

Despite never actually reaching No.1, Rolling Stone magazine still named ‘My generation’ the 11th greatest song of all time (Source). The British music magazine New Musical Express (NME), noted that the song “encapsulated the angst of being a teenager,” and was a “nod to the mod counterculture” (Source).

Pete Townshend. Source: Rnrchemist

The Who‘s guitarist, Pete Townshend, apparently wrote “My Generation,” on his 20th birthday (19th May 19th, 1965), while riding a train from London to Southampton for a television appearance. He claims that it was never meant to be the battle cry for young mod rebels that it went on to become.

Rather it was intended to express Townshend’s fears about ‘the impending strictures of adult life’. He preferred to stay young, free and experimental.

I am not having any teenage angst issues or fearing the very current strictures of adult life. I am simply using a play of the song’s title here in order to discuss a new year’s resolution I have made regarding the SoPD website over the never 12 months.

Let me explain.

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EDITORIAL: That Pfizer news

On Saturday 7th January, 2018, one of the world’s largest pharmaceutical companies – Pfizer – announced that it was abandoning research efforts focused on finding new drugs for Alzheimer’s and Parkinson’s. 

Naturally, the Parkinson’s and Alzheimer’s communities reacted with disappointment to the news, viewing it as a demoralising tragedy. And there was genuine concern that other pharmaceutical companies would follow suit in the wake of this decision.

Those fears, however, are unfounded.

In today’s post we will look at some of the reasons underlying Pfizer’s decision, why our approach to failure is wrong, why Pfizer will definitely be back, and what the Parkinson’s community can do about it all.


Photo by David Kovalenko on Unsplash

1. Our approach to failure

I am currently reading “Black box thinking: The Surprising Truth About Success“. It is a really interesting book by journalist Matthew Syed that investigates how we approach to failure.

Matthew Syed. Source: Amazon

In the first chapter of his book, Syed makes comparisons between the way the aviation industry and the medical profession approach failure, pointing out the processes that follow situations when a disasters occur. In the aviation industry, when any event occurs there is a major investigative process that starts with the recovery of the black boxes. The aviation industry uses this system of investigation to learn from every single incident. It makes the information available to all and this helps with re-thinking everything from cockpit ergonomics and design to air traffic controller procedures. Even the airline companies are keen to be seen to be involved in this process of investigation. Failure, while unfortunate, is not shameful or stigmatising, but rather embraced and enlightening. 

In addition, Syed points out that when an airline pilot sits down in his/her cockpit, their neck is also on the line if something goes wrong. Thus, it is in their best interest that the flight should be successful. And this is another reason why the aviation industry takes the reporting of failure so seriously. Everyone benefits from learning from previous situations. And all of this comes together with the observation that 2017 was the safest year on record for flying (based on deaths/flights – Source).

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When GCase is away, the GSLs will play

 

 

New research published in the last week provides further experimental support for numerous clinical trials currently being conducted, including one by the biotech company Sanofi Genzyme.

Researchers have demonstrated that tiny proteins which usually reside on the outer wall of cells could be playing an important role in the protein clustering (or aggregation) that characterises Parkinson’s

In today’s post we will look at this new research and discuss what it could mean for the on going clinical trials for Parkinson’s. 


Source: Stevedalepetworld

The proverb ‘When the cat is away, the mice will play’ has Latin origins.

Dum felis dormit, mus gaudet et exsi litantro (or ‘When the cat falls asleep, the mouse rejoices and leaps from the hole’)

It was also used in the early fourteenth century by the French: Ou chat na rat regne (‘Where there is no cat, the rat is king’).

And then Will Shakespeare used it in Henry the Fifth(1599), Act I, Scene II:

Westmoreland, speaking with King Henry V, Gloucester, Bedford, Exeter and Warwick
“But there’s a saying very old and true,
‘If that you will France win,
Then with Scotland first begin:’
For once the eagle England being in prey,
To her unguarded nest the weasel Scot
Comes sneaking and so sucks her princely eggs,
Playing the mouse in absence of the cat,
To tear and havoc more than she can eat”

The phrase first appears in its modern form in the United States in the literary and political magazine The Port folio in 1802 (2; 323):

Interesting. But what does any of this have to do with Parkinson’s?

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Multiple System Atrophy: A prion disease?

‘Parkinsonisms’ refer to a group of neurological conditions that cause movement features similar to those observed in Parkinson’s disease. They include multiple system atrophy (MSA) and Progressive supranuclear palsy (PSP) and idiopathic Parkinson’s.

Newly published research now shines a light on a possible mechanism for differentiating between multiple system atrophy and idiopathic Parkinson’s.

In today’s post we will look at what multiple system atrophy is, review the new research report, and discuss what these results could mean for the Parkinson’s community.


Brain immaging of multiple system atrophy–related spatial covariance pattern (MSARP) and Parkinson disease–related spatial covariance pattern (PDRP). Source: Neurology

For a long time I have been looking to write a piece of Multiple system atrophy.

I have been contacted by several readers asking for more information about it, and the only thing really delaying me – other than the tsunami of Parkinson’s related research that I am currently trying to write posts for – was the lack of a really interesting piece of research to base the post around.

Guess what came into my inbox yesterday:

Title: Familial Parkinson’s point mutation abolishes multiple system atrophy prion replication.
Authors: Woerman AL, Kazmi SA, Patel S, Aoyagi A, Oehler A, Widjaja K, Mordes DA, Olson SH, Prusiner SB.
Journal: Proc Natl Acad Sci U S A. 2017 Dec 26. pii: 201719369.
PMID: 29279394

This is a really interesting piece of research, that continues a line of other really interesting research.

And if it is independently replicated and verified, it will have massive implications for the Parkinson’s community, particularly those affected by Multiple System Atrophy.

But before we deal with that, let’s start with the obvious question:

What is Multiple System Atrophy?

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Novartis focuses on improving PARKIN control

Last week, as everyone was preparing for Christmas celebrations, researchers at the pharmaceutic company Novartis published new research on a gene that is involved with Parkinson’s, called PARKIN (or PARK2).

They used a new gene editing technology – called CRISPR – to conduct a large screening study to identify proteins that are involved with the activation of PARKIN.

In today’s post we will look at what PARKIN does, review the research report, and discuss how these results could be very beneficial for the Parkinson’s community.


Source: Novartis

As many people within the Parkinson’s community will be aware, 2017 represented the 200th anniversary of the first report of Parkinson’s disease by James Parkinson.

It also the 20th anniversary of the discovery of first genetic mutation (or variant) that increases the risk of developing Parkinson’s. That genetic variation occurs in a region of DNA (a gene) called ‘alpha synuclein’. Yes, that same alpha synuclein that seems to play such a critical role in Parkinson’s (Click here to read more about the 20th anniversary).

In 2018, we will be observing the 20th anniversary of the second genetic variation associated with Parkinson.

That gene is called PARKIN:

Title: Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
Authors: Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N
Journal: Nature. 1998 Apr 9; 392(6676):605-8
PMID: 9560156

In 1998, Japanese researchers published this report based on 5 individuals from 4 Japanese families who were affected by juvenile-onset Parkinson’s. In family 1, the affected individual was a female, 43 years old, born of first-cousin parents, and her two younger brothers are healthy. Her condition was diagnosed in her teens and it had then progressed very slowly afterwards. Her response to L-dopa was very positive, but L-dopa-induced dyskinesia were frequent. In family 2-4, affected individuals (born to unrelated parents) exhibited very similar clinical features to the subject in family 1. The age of onset was between 18 to 27 years of age.

Using previous research and various techniques the investigators were able to isolate genetic variations that were shared between the 5 affected individuals. They ultimately narrowed down their search to a section of DNA containing 2,960 base pairs, which encoded a protein of 465 amino acids.

They decided to call that protein PARKIN.

PARKIN Protein. Source: Wikipedia

How much of Parkinson’s is genetic?

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Inhibiting LRRK2: The Denali Phase I results

Denali

This week Denali Therapeutics released the results of a phase I clinical trial of their primary product, called DNL-201.

DNL-201 is a LRRK2 inhibitor that the company is attempting to take to the clinic for Parkinson’s disease. 

In today’s post we will look at what LRRK2 is, how an inhibitor might help in Parkinson’s, and what the results of the trial actually mean.


Wonder_Lake_and_Denali

Denali. Source: Wikipedia

Denali (Koyukon for “the high one”; also known as Mount McKinley) in Alaska is the highest mountain peak in North America, with a summit elevation of 20,310 feet (6,190 m) above sea level. The first verified ascent to Denali’s summit occurred on June 7, 1913, by four climbers Hudson Stuck, Harry Karstens, Walter Harper, and Robert Tatum.

Tatum (left), Karstens (middle), and Harper (right). Source: Gutenberg

Robert Tatum later commented, “The view from the top of Mount McKinley is like looking out the windows of Heaven!”

More recently another adventurous group associated with ‘Denali’ have been trying to scale lofty heights, but of a completely different sort from the mountaineering kind.

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A virtual reality for Parkinson’s: Keapstone

 

parkinsons_virtual_biotech_graphic

 

In 2017, Parkinson’s UK – the largest charitable funder of Parkinson’s disease research in Europe – took a bold step forward in their efforts to find novel therapies.

In addition to funding a wide range of small and large academic research projects and supporting clinical trials, they have also decided to set up ‘virtual biotech’ companies – providing focused efforts to develop new drugs for Parkinson’s, targeting very specific therapeutic areas.

In today’s post we will look at the science behind their first virtual biotech company: Keapstone.


Virtual_Reality_Oculus_Rift

A virtual world of bioscience. Source: Cast-Pharma

I have previously discussed the fantastic Parkinson’s-related research being conducted at Sheffield University (Click here to read that post). Particularly at the Sheffield Institute for Translational Neuroscience (SITraN) which was opened in 2010 by Her Majesty The Queen. It is the first European Institute purpose-built and dedicated to basic and clinical research into Motor Neuron Disease as well as other neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease.

The research being conducted at the SITraN has given rise to multiple lines of research following up interesting drug candidates which are gradually being taken to the clinic for various conditions, including Parkinson’s.

It’s all very impressive.

And apparently I’m not the only one who thought it was impressive.

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