Tagged: disease

Is there NOP hope for Parkinson’s?

Please do not misread the title of this post!

Compounds targeting the Nociceptin receptor (or NOP) could provide the Parkinson’s community with novel treatment options in the not-too-distant future.

In pre-clinical models of Parkinson’s, compounds designed to block NOP have demonstrated neuroprotective properties, while drugs that stimulate NOP appear to be beneficial in reducing L-dopa induced dyskinesias. 

In today’s post we look at exactly what NOP is and what it does, we will review some of the Parkinson’s-based research that have been conducted so far, and we will look at what is happening in the clinic with regards to NOP-based treatments.


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Source: LUMS

On the surface of every cell in your body, there are lots of small proteins that are called receptors.

They are numerous and ubiquitous.

And they function act like a ‘light switch’ – allowing for certain biological processes to be initiated or inhibited. All a receptor requires to be activated (or blocked) is a chemical messenger – called a ligand – to come along and bind to it.

An example of a receptor on a cell. Source: Droualb

Each type of receptor has a particular structure, which is specific to certain shaped ligands (the chemical messenger I mentioned above). These ligands are floating around in the extracellular space (the world outside of the cell), having been released (or secreted) by other cells.

And this process represents one of the main methods by which cells communicate with each other.

By binding to a receptor, the ligand can either activate the receptor or alternatively block it. The activator ligands are called agonists, while the blockers are antagonists.

Agonists_and_antagonists

Agonist vs antagonist. Source: Psychonautwiki

Many of the drugs we currently have available in the clinic function in this manner.

For example, with Parkinson’s medications, some people will be taking Pramipexole (‘Mirapex’ and ‘Sifrol’) or Apomorphine (‘Apokyn’) to treat their symptoms. These drugs are Dopamine agonists because they bind to the dopamine receptors, and help with dopamine-mediated functions (dopamine being one of the chemicals that is severely in the Parkinsonian brain). As you can see in the image below the blue dopamine agonists can bypass the dopamine production process (which is reduced in Parkinson’s) and bind directly to the dopamine receptors on the cells that are the intended targets of dopamine.

Source: Bocsci

There are also dopamine antagonists (such as Olanzapine or ‘Zyprexa’) which blocks dopamine receptors. These drugs are not very helpful to Parkinson’s, but dopamine antagonist are commonly prescribed for people with schizophrenia.

Are there other receptors of interest in Parkinson’s?

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Making. It. Personal.

This is one of those post (read: rants) where I want to put an idea out into the ether for someone to chew on. It starts with a very simple question:

Why is ‘the drug’ the focus of a clinical trial?

If our goal is to find beneficial therapies for people with Parkinson’s, then the way we currently clinically test drugs is utterly nonsensical.

And if we do not change our “we’ve always done it this way” mindset, then we are simply going to repeat the mistakes of the past. Others are changing, so why aren’t we?

In today’s post, we will consider one possible alternative approach.


I hope you know who Grace Hopper is – if not, click here. Source: Mentalfloss

Why is ‘the drug‘ the focus of a clinical trial?

The way we clinically test drugs makes absolutely no sense when you actually stop and think about it.

Other medical disciplines (such as oncology) have woken up to this fact, and it is time for the field of Parkinson’s research to do this same.

Let me explain:

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Something is interesting in the state of Denmark

 

 

Gaucher disease is a genetic disorder caused by the reduced activity of an enzyme, glucocerebrosidase. This enzyme is produced by a region of DNA (or a gene) called GBA – the same GBA gene associated with a particular form of Parkinson’s.

Recently, a Danish company has been testing a new drug that could benefit people with Gaucher disease.

It is only natural to ask the question: Could this drug also benefit GBA-associated Parkinson’s?

In today’s post, we will discuss what Gaucher disease is, how this experimental drug works, and why it would be interesting to test it in Parkinson’s.


Will Shakespeare. Source: Ppolskieradio

The title of this post is a play on words from one of the many famous lines of William Shakespeare’s play, Hamlet.

The original line – delivered by Marcellus (a Danish army sentinel) after the ghost of the dead king appears – reads: If the authorities knew about the problems and chose not to prevent them, then clearly something is rotten in the state of Denmark.

(Act 1, Scene 4)

The title of this post, however, is: Something is interesting in the state of Denmark

This slight change was made because certain Danish authorities know about the problem and they are trying to prevent it. The ‘authorities’ in this situation are some research scientists at a biotech company in Denmark, called Orphazyme.

And the problem is Parkinson’s?

No, the problem is Gaucher disease.

Huh? What is Gaucher disease?

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“What’s the evolutionary advantage of Parkinson’s?”

Each year King’s College London holds the Edmond J. Safra Memorial Lecture. It is a public event – exploring cutting-edge research on Parkinson’s – held in honour of the late philanthropist and financier, Mr Edmond J Safra, .

I was lucky enough to attend this year’s event (entitled A vision of tomorrow: How can technology improve diagnosis and treatment for Parkinson’s patients?). It highlighted the fantastic research being carried out by Professor Marios Politis and his team.

During the Q&A session of the event though, a question was asked from the audience regarding what the evolutionary advantage of Parkinson’s might be. The question drew a polite chuckle from the audience.

But the question wasn’t actually as silly as some might think.

In today’s post we look at some evidence suggesting an evolutionary advantage involving Parkinson’s.


King’s College London Chapel. Source: Schoolapply

Despite the impressive name, King’s College London is not one of the grand old universities of England.

Named after its patron King George IV (1762-1830), the university was only founded in 1829 (compare this with 1096 for Oxford and 1209 for Cambridge; even silly little universities like Harvard date back further – 1636). The university is spread over five separate campuses, geographically spread across London. But if you ever get the chance to visit the main Strand campus, ask for the chapel and take a moment to have a look – it is very impressive (the image above really doesn’t do it justice).

As I mentioned in the intro, each year King’s College London holds the Edmond J. Safra Memorial Lecture. It is an event that is open to the public and it involves a discussion regarding innovative new research on Parkinson’s. The evening is held in honour of the late Mr Edmond J Safra.

Edmond J. Safra. Source: Edmondjsafrafoundation

This year, Professor Marios Politis and members of his research group were presenting lectures on “How can technology improve diagnosis and treatment for Parkinson’s”. The lectures were very interesting, but the reason I am writing about it here is because during the question and answer session at the end of the lectures, the following question was asked:

“What’s the evolutionary advantage of Parkinson’s?”

Given the debilitating features of the condition, the audience was naturally amused by the question. And there was most likely several people present who would have thought the idea of any evolutionary advantage to Parkinson’s a ridiculous concept.

But it’s not.

And there is actually research to suggest that something evolutionary could be happening with Parkinson’s.

?!?!? What do you mean?

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The dilemma of success

Late last year, I wrote a post for Parkinson’s UK‘s excellent blog on Medium.

My piece was called the Dilemma of Success, and it explored a hypothetical situation that we may very well face in the not-so-distant future.

Optimistic as I am about the future of Parkinson’s research, I think this is a very serious issue – one which the Parkinson’s community needs to discuss and start planning for. I am re-posting it here today as I am keen for some thoughts/discussion on this matter.

 
BP

Lord Robert Baden-Powell. Source: Utahscouts

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

“When did Noah build the ark?”

My fellow scouts and I looked at each other. Some of us were wondering if the guy had completely lost the plot and somehow thought that it was Sunday morning and he was doing the sermon. Others seriously looked like they were trying to calculate an exact date.

He waited a moment for one of us to offer up some idiotic attempt at an answer, before he solemnly said:

“Before the rain”

It’s one of those childhood moments that didn’t make sense at the time, but comes back to haunt you whenever you can foresee certain troubles coming over the hill towards you.


The dilemma of success

It will be nice to have this problem, but it will still be a problem.
And we need to plan for it

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Happy birthday: Silverstein Foundation

Over the last 12 months, the Silverstein Foundation has quickly established itself as a major focused force in the fight against Parkinson’s.

And when I say ‘focused’, I mean ‘focused’ –  the foundation is “actively pursues and invests in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in glucocerebrosidase (GBA) mutation carriers”.

But the output of this effort may well have major benefits for the entire Parkinson’s community.

In today’s post, we will discuss what GBA is, how it functions inside cells, its association with Parkinson’s, and what all of this GBA focused research being funded by the Silverstein Foundation could mean for the Parkinson’s community.


Jonathan Silverstein. Source: Forbes

This is Jonathan Silverstein.

He’s a dude.

He is also a General Partner and a Co-Head of Global Private Equity at OrbiMed – the world’s largest fully dedicated healthcare fund manager. During his time at OrbiMed, the company has invested in healthcare companies that have been involved with over 60 FDA approved products.

In February 2017, he was diagnosed with Parkinson’s disease at just 49 years of age.

Rather than simply accepting this diagnosis, however, Mr Silverstein decided to apply the skills that he has built over a long and successful career in funding biotech technology, and in March 2017, he and his wife, Natalie, set up the Silverstein Foundation.

They raised $6 million from donors and then provided another $10 million of their own money to fund the endeavour, which has funded a dozen research projects and started a new company called Prevail Therapeutics (we’ll come back to this shortly).

Source: Businesswire

The foundation has just one mission: “to actively pursue and invest in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in GBA mutation carriers”

And it seeks to address this by achieving three goals:

  1. to find a way to halt the progression of Parkinson’s with GBA.
  2. to identify regenerative approaches to replace the damaged/lost cells
  3. to find preventative measures

What is ‘GBA’?

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One black sheep per week

Each time a cell divides, the DNA inside the resulting pair of cells has changed slightly. These small alterations – known as genetic mutations – provide a method by which an organism can randomly determine traits that may be beneficial.

New research indicates that in certain parts of the brain, post-mitotic (non-dividing) cells are taking on as many as one mutation per week across the span of our lives. This results in thousands of genetic variations accumulating in each cell by the time we eventually pass away in old age.

In today’s post we will review new research and consider what this gradual build up of genetic mutations could mean for our understanding of neurodegenerative conditions, like Parkinson’s.


Source: Pexels

Coming from the back waters of third world New Zealand, you will understand that sheep hold a very special place in my heart.

I grew up a simple country lad, and each year I had a pet lamb that I would raise and train to do silly tricks in the hope of impressing the judges at the annual agricultural/farm day at school. In addition to instilling me with a crazy fanaticism for the sport (read: religion) of rugby, my parents figured that having a pet lamb each year would teach me a sense of responsibility and a sort of discipline.

I’m not really sure how this practice has influenced my later life, but I certainly do have very fond memories of those early years (the first lamb was named ‘Woolly’, the 2nd lamb was named ‘Woolly2’, the third lamb was actually a goat – bad lambing season – which I named ‘Billy the kid’, the 4th lamb was named ‘MacGyver’,…).

Lots of happy memories.

Source: Countryliving

But as I grew into the teenage years, there was one thing that really bothered me with regards to my pet lambs.

It was that whole negative stigma associated with the ‘black sheep’.

Why, I would wonder, was it the ‘black sheep of the family’ that was the bad kid? And why was the one black sheep in every flock considered the worst of the bunch?

Source: theodysseyonline

Why was this association applied to sheep?

Why not dogs? Or cows? Why do we pick on sheep?

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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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