Author: Simon

I am the Deputy Director of Research at the Cure Parkinson's Trust. Before that I was working as a Parkinson's research scientist at the University of Cambridge where I conducted both clinical- and lab-based research on Parkinson's. I have worked in the Parkinson's research field for over 15 years - both academically and in biotech ventures. In addition, I am the president of my local Parkinson's UK support branch in North Hertfordshire. All of my views/opinions expressed here are solely my own, and may not reflect the views of my employer or associated parties.

Trying to LIMP-2 the lysosome

~ Simon ~ 6 Comments

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Lysosomes are small bags of enzymes that are used to break down material inside of cells – digesting newly absorbed food or recycling old/used proteins and rubbish. Recently researchers have been discovering increasing evidence that points towards dysfunction in lysosomes as a key influential player in neurodegenerative conditions, like Parkinson’s.

There are several Parkinson’s genetic risk factors associated with lysosomal function (GBA being the obvious one), that can increase one’s risk of developing Parkinson’s.

But there is also data indicating that individuals without any of these risk factors may also have reduced lysosomal activity. And recently researchers have identified one possible explanation.

In today’s post, we will explore what lysosomes are, investigate how they maybe involved with Parkinson’s, review what the new data reports, and discuss how this information might be useful.

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Type of endocytosis. Source: Slidemodel

On a continual basis, cells inside your body are absorbing material from the world around them with the aim of collecting all that they need to survive. They do this predominantly via a process called endocytosis, in which a small part of the cell membrane envelopes around an object (or objects) and it is brought inside the cell.

As the section of cell membrane enters the interior of the cell, it detaches from the membranes and forms what is called an endosomes (sometimes it is also called a vacuole). Once inside, the endosome transported deeper into the interior of the cells where it will bind to another small bag that is full of digestive enzymes that help to break down the contents of the endosome.

This second bag is called a lysosome.

Lysosomes

How lysosomes work. Source: Prezi

Once bound, the lysosome and the endosome/vacuole will fuse together and the enzymes from the lysosome will be unleashed on the material contained in the vacuole. The digestion that follows will break down the material into more manageable components that the cell needs to function and survive.

This enzymatic process works in a very similar fashion to the commercial products that you use for washing your clothes.

Enzymatic degradation. Source: Samvirke

The reagents that you put into the washing machine with your clothes contain a multitude of enzymes, each of which help to break down the dirty, bacteria, flakes of skin, etc that cling to your clothes. Each enzyme breaks down a particular protein, fat or such like. And this situation is very similar to the collection of enzymes in the lysosome. Each enzyme has a particular task and all of them are needed to break down the contents of the endosome.

Interesting, but what does this have to do with Parkinson’s?

Continue reading “Trying to LIMP-2 the lysosome” →

Being ly-mphatic about drainage issues

~ Simon ~ 6 Comments

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The lymphatic network is an important part of our body’s defense system. It is made up of an enormous web of vessels and nodes which help to protect us from infection and disease.

This network transports a colourless fluid (called lymph), which serves two primary functions: 1.) it contains infection-fighting white blood cells that help in immune responses, and 2.) it functions as a ‘drainage system’ – allowing excess fluid from organs to be extracted and shifted to the blood system for excretion.

Recently, researchers reported something interesting about the lymphatic system in people with Parkinson’s: the rate of flow around the brain is slower.

In today’s post, we will discuss what the lymphatic system is, review what the new research found, and look at how this new information could potentially be used to help treat conditions like Parkinson’s.

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Source: Thinkery

So picture this if you will:

The weather reporter would later say that it was “a month of rain in the matter of an hour“, but in the midst of the summertime mêlée I was standing bare foot, ankle deep in my rapidly flooding courtyard, trying to clear the blocked storm drain with a long metal pole.

My tee-shirt and shorts were soaked, and… oh yeah, there was lots of thunder and (more importantly) lightning.

Source: KalingaTV

Now, I am a rather tall individual (6’8 ~ 2m 7cm on my good days), and looking back now I can appreciate that standing ankle deep in water holding a long metal pole high in the air (to gather enough downward force to unplug the drain) in the middle of a lightning storm was probably not one of my best moments.

Luckily, my neighbour – a plumber and 3-4 fold smarter than me – kindly decided to take pity on his slow-witted nearby resident. He leapt into the situation and resolved it all in the blink of an eye.

Source: Independent

Since that moment I have religiously maintained a clear storm drain, and taken to deriving great pleasure in keeping other drainage systems about the house clear and flowing free.

I’m happy for you, but what does this have to do with Parkinson’s?

Well, very recently researchers have reported that a different kind of drainage issue might be at play in many cases of Parkinson’s.

What on Earth do you mean?!?

Continue reading “Being ly-mphatic about drainage issues” →

Monthly Research Review – January 2021

~ Simon ~ 1 Comment

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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 the previous 4 weeks.

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

Today’s post is a review of Parkinson’s research during the month of January 2021.

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So, what happened during January 2021?

In world news:

January 6th – the platypus genome was published. Reseachers explore how one of mother nature’s oddities became so odd (Click here to read more about this).

January 6th – Using a recently developed gene-editing technique, researchers reported that they could partially correct the accelerated aging disorder of progeria, extending the lifespan of mice with the associated genetic variation (Click here to read more about this).

January 7th – While the world is more focused on the rollout of the company’s COVID vaccine, researchers at BioNTech published a research report in which they had designed an mRNA vaccine that delayed the onset of and reduced the severity of multiple sclerosis-like disease in mice (Click here to read more about this).

January 26 – The number of confirmed COVID-19 cases exceeded 100 million worldwide.

January 28th – A day that some of the absurdity of the stock market was openly revealed. Wall Street institutions cried “it’s not fair if everyone else can manipulate the market”, as the GameStop share price rise messed up their own manipulations (Now we suddenly need regulation?!?). Free markets indeed (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 2021, there were 1,235 research articles added to the Pubmed website with the tag word “Parkinson’s ” attached (10,584 for all of 2020). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 6 pieces of Parkinson’s news

Continue reading “Monthly Research Review – January 2021” →

The age-associated changes of PARKIN

~ Simon ~ 3 Comments

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Tiny variations in a region of DNA referred to as “Parkin” are associated with an increased risk of developing Parkinson’s (particularly young onset forms of the conditions). The Parkin DNA provide the instructions for making a protein that is involved with many functions inside cells.

New research indicates that as we age, Parkin protein becomes less available. In fact, by the time we turn 50 years of age, “Parkin is largely insoluble”, meaning that the majority of the protein is no longer able to do its job.

This shift appears to involve oxidation changes.

In today’s post, we will discuss what Parkin and oxidation are, how Parkin might be affected by oxidation, and how this information might be useful to treating Parkin-associated Parkinson’s.

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Me (I wish) before 27. Source: Pinterest

I don’t know about you, but 27 was my peak.

Before my 27th birthday, I could run around all over the place – acting like an idiot, with all the energy in the world. I was invincible and having lots of fun. And yes, some vices might have been involved – I would drink myself blind on a Friday night, wake up fresh the next day and do it all merrily again.

Me before 27. Source: Thefix

But then, my 27th birthday came along and I woke up the next day tired and feeling… fatigued. Weary even. And definitely with less enthusiasm than I had before I passed out the night before. My father called it a “hang-over” (which up until that time I had naively/idiotically thought I was immune to).

Me, before (left) and after 27 (right). Source: Wanna-joke

But I gradually developed this sinking feeling that it was something else.

Something more sinister.

It was as though something had changed. Something inside of me.

And I distinctly remember a moment of realisation, when I asked “Am I getting old???”

My father saw my concern and gave me sage advice (“It’s like I always say, aging ain’t for sissies“), and with that I changed my ways.

Source: DS

Since that moment, I have been fascinated by the biology of aging, particularly in the context of Parkinson’s (age is the main correlate with neurodegenerative conditions like Parkinson’s and Alzheimer’s). So it was with great interest that I read a manuscript in November last year that had been posted on the openly-available preprint database bioRxiv.

What did the manuscript say?

Continue reading “The age-associated changes of PARKIN” →

2021: Wish list

~ Simon ~ 8 Comments

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

We would rather focus our attention on interesting ideas and trends, discussing what we hope to see happen in the future, and exploring different ways and means by which change could occur. It is done in the hope that someone will pick up the ball and run with it (ideally, they already have the ball!).

In today’s post, we will outline the SoPD wish list for 2021. 

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My parents recently took my young neice and nephew to the Pūkorokoro Miranda Shorebird Centre, just south of Auckland city in New Zealand. There, the kids were introduced to Bar-tailed Godwits – a long-billed, long-legged wading bird.

Bar-tailed godwit. Source: Wikipedia

To look at them, there is nothing very remarkable about Godwits… that is, of course, until you look at how far they migrate each year.

You see, Godwits have a rather busy calendar, with a lot of their time being spent racking up air miles.

These little bird fly from Alaska to New Zealand and back (via either China) every year!

Source: Wingthreads

The round-trip is over 29,000 km (or 18,000 miles), and the journey across the Pacific Ocean from Alaska to New Zealand is the longest non-stop flight of any bird in the world (in fact, it is the longest trip made without pausing for food by any animal – Source).

My nephew is 8 and my neice is 10.

They were rather “meh” about the birds, and somewhat more impressed by the ice cream that they got for the ride home.

Source: Morellisices

I on the otherhand was fascinated with these little birds when my mum was telling me about their day out. So many questions were popping into my head (like the obvious “what possesses them to fly that far?!?” and “how on Earth do they know where they are going in the middle of the Pacific ocean?!?“). But I was equally impressed by how much they could accomplish in the span of a 12 month period (I mean: 30,000 km!!!).

And naturally that got me thinking about the annual “Wish list” post for the SoPD website, which discusses what I am hoping to see from Parkinson’s research over the next 12 months (beyond the obvious curative therapies).

In today’s post, we discuss our wish list for Parkinson’s research in 2021.

Continue reading “2021: Wish list” →

The road ahead: 2021

~ Simon ~ 4 Comments

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At the start of each year, it is a useful practise to layout what is planned over the next 12 months. The events that are scheduled for the year to come, so that we can keep an eye out for them. Obviously, where 2021 will end actually is unpredictable, but an outline of what is scheduled over the next 365 days will hopefully provide us with a useful resource for helping to manage expectations.

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, the genetics and biology of the condition, novel symptomatic therapies, and other aspects of Parkinson’s, my primary focus is generally on the science seeking to slow, stop or reverse the condition.

In this post, I will try to map out some of what is scheduled to occur in 2021 with regards to clinical research focused on disease modification for Parkinson’s. I will also note aspects of ongoing research where I will be hoping to see an update on progress. It will be an extremely (read: ridiculously) long post, but it will hopefully give readers a feel for what the landscape looks like for research focused on disease modification for Parkinson’s.

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Source: Kickstarter

Cartography is the study and practice of mapping things out. It has been used for centuries to provide graphic representations of what stuff looks like to help us to better understand things.

The word cartography comes from the Greek words χάρτης or chartēs (meaning “papyrus, sheet of paper”) and γράφειν or graphein (meaning “to write”).

According to Wikipedia, the fundamental objectives of traditional cartography are to:

  • Set the map’s agenda and select traits of the object to be mapped.
  • Represent the terrain of the mapped object on flat media.
  • Eliminate characteristics of the mapped object that are not relevant to the map’s purpose.
  • Reduce the complexity of the characteristics that will be mapped.
  • Orchestrate the elements of the map to best convey its message to its audience.

At the start of each year, the SoPD publishes a horizon scanning post where we take a cartography-like approach towards laying out the landscape of clinical research focused on disease modification for Parkinson’s for the next 12 months.

Source: Rand

We try to “set the agenda” and “select traits” to look out for in 2021. We also try to “represent the terrain” and “reduce the complexity of the characteristics” (well,… at least we will try to!) in a manner that will “best convey” to the reader what the next 12 months may look like.

All of this is in an effort in better managing expectations about some of the research results that are coming down the pipe.

Continue reading “The road ahead: 2021” →

2020: Year in Review

~ Simon ~ 4 Comments

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In this end-of-year post, we review the Parkinson’s research that caught our attention at SoPD HQ in 2020.

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 2020.

And in the next SoPD post, we will conduct our annual horizon scan and consider what 2021 may have in store for us.

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Source: PhysicsWorld

More than any other year, 2020 saw the best and worst of us.

It was a ridiculous 365 days (you couldn’t make up half the stuff that happened – e.g. “bleach”), and also one of the most humbling periods of our lives. In many ways we came together and stepped up to face challenges (e.g. the COVID-19 vaccine efforts), and yet at that same time if you listen to any of the 24-hour idiotic noise we have never been so divided. Some of people showed tremendous courage (e.g. the front line medics), and others of us were found to be wanting and learnt how little (if any) fortitude we truly have.

It was a dreadful year, but at the same time one that has been strangely fascinating to experience.

And despite the setbacks brought on by the COVID-19 situation, there has been remarkable progress in the arena of Parkinson’s research and in today’s post we will do both a short and long review of 2020, according to research-related events/publications that we here at the SoPD thought were of note.

THE SHORT REVIEW: A top five

If we had to select a top 5 Parkinson’s research-related events/highlights of 2020, they would be:

Continue reading “2020: Year in Review” →

Monthly Research Review – December 2020

~ Simon ~ Leave a comment

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 December 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
  • Conferences/lectures
  • Other news
  • Review articles/videos

So, what happened during December 2020?

In world news:

December 2nd – The United Kingdom approved the Pfizer/BioNTech BNT162b2 vaccine for COVID-19.

December 8th – Nepal and China officially agree on Mount Everest’s actual height, which is 8,848.86m (0.86m higher than previously officially calculated).

December 9th – The SpaceX Starship prototype SN8 made a first test flight – reaching an altitude of 41,000 feet (12,500 metres) – at the company’s rocket facility in Boca Chica, Texas. The flight was a pretty spectacular feat of engineering (the landing not so much).

December 23rd – Scientists from The Wistar Institute (Philadelphia) reported a new class of compounds that uniquely combine direct antibiotic killing of pan drug-resistant bacterial pathogens with a simultaneous rapid immune response for combating antimicrobial resistance (Click here to read more about this and click here to read the press summary).

December 24th – The UK Government announced that the UK ‘decided not to stay in Erasmus‘ under the Christmas eve Brexit deal. The Erasmus exchange programme, which the UK joined in 1987, has allowed approximately 17,000 young UK citizens each year to study and work at universities across Europe, but more importantly has encouraged 32,000 EU students to come to the UK (approximately 200,000 students across the EU take part each year). In January, Boris Johnson assured MPs there was “no threat to the Erasmus scheme”. A replacement UK scheme named after computing pioneer Alan Turing will be set up (backed by £100 million in its first year), but the new scheme is not expected to fund students coming to the UK, which suggests UK universities will miss out on a source of income (>£200m a year – Click here and here to read more about this. (an absolute disaster for small UK universities).

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

In December 2020, there were 773 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (10,584 for all of 2020). 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 “Monthly Research Review – December 2020” →

PARP-kinson’s goes chlorogenic

~ Simon ~ 2 Comments

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For a long time it was been reported that coffee may be able to reduce the risk of developing Parkinson’s, but the mechansim by which this association could be occurring has remained elusive.

Now researchers from South Korea have discovered a biological pathway that could help to explain the protective association.

It involves a protein called PARP and a chemical called chlorogenic acid.

In today’s post, we will explore the research suggesting a link between coffee and a lower risk of Parkinson’s, discuss what PARP and chlorogenic acid are, and review the new research that may bring all four topics together.

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kaldi-adapted-from-uker

Kaldi the goat herder. Source: CoffeeCrossroads

Legend has it that in 800AD, a young Ethiopian goat herder named Kaldi noticed that his animals were “dancing”.

They had been eating some berries from a tree that Kaldi did not recognise, but being a plucky young fellow – and being fascinated by the merry behaviour of his four-legged friends – Kaldi naturally decided to self-experiment by eating some of the berries for himself.

The result?

He became “the happiest herder in happy Arabia” (Source).

This amusing encounter was apparently how humans discovered coffee. It is most likely a fiction as the earliest credible accounts of coffee-consumption emerge from the 15th century in the Sufi shrines of Yemen, but since then coffee has gone on to become one of the most popular drinks in the world.

coffee-cup-images-5

Fancy a cuppa? Source: Science-All

Interesting, but what does coffee have to do with Parkinson’s?

Continue reading “PARP-kinson’s goes chlorogenic” →

Prevail lands on a Lilly pad

~ Simon ~ 4 Comments

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2020 has been a dreadful year for most of the world – burdened by the outbreak and consequences of COVID-19. Despite this, there has been a steady stream of biotech acquisitions related to Parkinson’s which have helped to keep morale high in the PD research community.

In October alone, we saw the Portuguese pharmaceutical company Bial purchase GBA-associated Parkinson’s biotech firm Lysosomal Therapeutics (Click here to read more about this) and the acquisition of the inflammasome-focused biotech firm Inflazome was being bought by Roche (Click here to read more about this).

Today brought news of yet another pharmaceutical company – this time Eli Lilly – purchasing a Parkinson’s-focused biotech company (Prevail Therapeutics).

In today’s post, we will explore what Prevail Therapeutics does, why Eli Lilly might be so interested in this company, and why it could be an encouraging move for individuals with a sub-type of Parkinson’s.

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Colonel Eli Lilly. Source: SS

The civil war veteran, Colonel Eli Lilly started his pharmaceutical career in a drug store in Greencastle (Indiana) in 1869.

Several years later (in 1873) he shifted into the manufacturing of pharmaceuticals (in association with John F Johnston). Two years after that, Lily disolved their partnership, sold his assets, and used the proceeds to set up “Eli Lilly and Co” in Indianapolis.

Source: Wikimedia

He started the company in a rented building on the 10th May, 1876. He was 38 years old, with working capital of $1400 and just three employees. The first medicine that he produced was quinine – a drug used to treat malaria.

Since that humble start, the company (now more commonly known as just “Lilly”) has grown to become one of the 20 largest pharmaceutical companies in the world (Source), with offices in 18 countries and products sold in 125 countries (Source).

Lilly was the first company to mass-produce the polio vaccine and it was also one of the first pharmaceutical companies to produce human insulin using recombinant DNA. Lilly is currently the largest manufacturer of psychiatric medications, including Prozac (Source).

Today, the company employs approximately 38,000 people worldwide, and operates through two key business divisions:

  • Human Pharmaceutical Products, which involves the production and sale of prescription medications in the fields of endocrinology, oncology, cardiovascular health, and neuroscience
  • Animal Health Products, comprising the development and sale of treatments for domestic and farm animals

This is all very interesting, but what does any of it have to do with Parkinson’s?

This week the biotech world was alerted to the news that Eli Lilly was purchasing a biotech company that is focused on developing a novel treatment for a subtype of Parkinson’s.

That company is called Prevail Therapeutics.

What does Prevail Therapeutics do?

Continue reading “Prevail lands on a Lilly pad” →