Monthly Research Review – February 2021

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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 February 2021.

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

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So, what happened during February 2021?

In world news:

February 4th – More injections than infections – more people have now been vaccinated against Covid-19 than infected worldwide (Source).

February 15th – Ngozi Okonjo-Iweala elected as the seventh Director-General of the World Trade Organisation – a first for women and a first for Africa (Source).

 

February 17th – Researchers reported a high-performance polyethylene plastic made from renewable oils that is chemically recyclable (Source).

February 18th – Nasa’s Perseverance (“Percy”) rover was safely delivered to the surface of Mars (Source).

24 February – Ghana becomes the first country to receive vaccines through the COVAX vaccine-sharing initiative.

 

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

In February 2021, there were 1,228 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (2,463 for all of 2021 so far). 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 – February 2021”

Our approach to failure

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Recently the results of two large clinical trials in Parkinson’s were announced. Both indicated that the therapies involved had not demonstrated any impact on the progression of Parkinson’s. This disappointing news resulted in the usual headlines (“Epic failure” & “Clinical trial tanks”) from news outlets whose editors have obviously never lost anyone they cared about.

In addition, there has also been a useful chorus of “I told you so” and “We’re going the wrong way” coming from the back seat of the car, despite the fact that we haven’t seen any actual trial data yet, or the fact that they can’t propose any viable alternative approaches.

What is missing in all of this noise, however, is a better approach to failure. Not only an open and honest postmortem of what worked and didn’t work in the studies, but also better, more respectful ways of communicating results.

In today’s post, we will discuss our approach to failure.

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PART 1. POSTMORTEM

The book I gift the most is Sherwin Nuland’s “How we die”.

As a rule, I am selective as to who I gift this to, never for Christmas or birthdays, and I always remind the receiver of the gift that “you should not judge a book by its cover”.

This book is so precious.

A poetic set of reflections from a medical doctor who has sent his entire career watching ‘life’s final chapter’. There is science, wisdom and beauty on every single page. Nuland has such a wonderful way with words, and I find myself constantly going back to this book and finding something new.

Sherwin Nuland (1930 – 2014). Source: Theparisreview

My favourite part of the entire book is chapter 11.

Throughout the first half of the book, Nuland pushes the argument for returning some dignity to our last days of life. Rather than prolonging suffering in a futile effort to extend life a few short months, he implores the reader to let nature simply take its course.

But all of this changes in chapter 11, where he describes the moment his brother Harvey called him on the phone and told him he had been diagnosed with terminal cancer.

Source: Lawtech

In an instant everything changed. The context had shifted, and instead of “let nature simply take its course”, Nuland recalls how his thinking immediately became “we have to do whatever it takes to keep my brother alive”. (And I’m not ruining the book by sharing this spoiler – there is so much more in this book. It should be required reading for first year medical students).

My second most gifted book is “Black box thinking: The Surprising Truth About Success by Matthew Syed.

Matthew Syed. Source: Amazon

It investigates how we approach failure, and the first chapter describes everything that is wrong with how we currently conduct clinical trials.

What does it say?

Continue reading “Our approach to failure”

The basket case

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One of the more interesting pieces of clinical trial news in 2020 was the publication of the results of a “basket study” for neurological conditions. This was a trial that involved a drug being tested on a selection of neurodegenerative conditions, rather than just one condition.

Between December 2013 to May 2017, researchers recruited a total of 29 individuals with Alzheimer’s, 14 with progressive supranuclear palsy (PSP) and 30 with corticobasal syndrome. These participants were intravenously injected with the same drug (TPI-287 – a microtubule stabilizer) once every 3 weeks for 9 weeks (with an optional 6-week open-label extension).

Although the findings of the study did not support further development of TPI-287 for tauopathies, the overall structure of the study represents an interesting example of how researchers are taking different approaches to investigating neurodegenerative conditions.

In today’s post, we will discuss novel clinical trial designs (“baskets and umbrella”) and other examples of research efforts to better understand neurodegeneration as a whole.

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Source: HuffPost

It was when my daughter turned 3 years old that the psychological warfare really started.

And I remember the moment of realisation very clearly: It began with her desire for a pet dog.

Up until that point in time, she had limited experience with dogs and her negotiation strategies centred solely around crying. I think she loved “the idea” of a dog, but she was generally quite timid around them. Regardless, she gradually began applying pressure (read: lots of crying) on us to get a dog.

And said pressure began to build rapidly (read: frequent episodes of lots of crying).

Source: Focus

Now my wife is definitely not a dog person (“wet, filthy, smelly things“). I on the other hand quite like dogs, but I was utterly, utterly, utterly opposed to getting one because I know full well who will be lumped with the mid-winter late night “walkies” two years down the line: me!

The pressure from our daughter continued to increase, however, until we finally had to sit down with her and explain that we were not going to be getting a dog. On the surface, it looked like she handled this news very well (that is to say: she did not cry). She simply accepted the situation, got up and left the room, saying “Ok”.

My wife and I looked at each other and thought “problem solved”.

The next morning, however, this picture was waiting for us on the kitchen table:

I kid you not.

That’s my daughter and her pet dog (“Linguine“) on the right, and I’m the big, cross-eyed, bad guy on the left.

Since that time the psychological manoeuvring has only become more sophisticated (the teenage years are still a few years away, but I am already absolutely terrified!).

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

Continue reading “The basket case”

Trying to LIMP-2 the lysosome

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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

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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”

The age-associated changes of PARKIN

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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

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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”

PARP-kinson’s goes chlorogenic

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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

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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”

TGF-beta: The Parkinson’s superfamily?

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A lot of Parkinson’s research has focused on a neurotrophic factor called glial cell-derived neurotrophic factor (or GDNF).

But GDNF only represents a small fraction of a much larger class of neurotrophic factors, called the Transforming growth factor-β (TGF-β) superfamily.

Recently, researchers have been investigating some of the other TGF-β family members in preclinical models of Parkinson’s and they have been making some interesting discoveries.

In today’s post, we will discuss what is meant by neurotrophic factor, explore who else is in the TGF-β superfamily, and look at two recent reports highlighting family members in the context of Parkinson’s.

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Different types of cells in the brain. Source: Dreamstime

Glial cells are the support cells in the brain. While neurons are considered to be the ‘work horses’ of neurological function – passing messages and storing memories – glial cells are in the background making sure that neurons are protected and well nurtured.

There are different types of glial cells, including astrocytes, oligodendrocytes and microglia. And each type has a specific function, for example microglia are the brain’s resident immune cells checking up on the health of the neurons while oligodendrocytes provide the neurons with a protective covering (called myelin sheath) which also helps to speed up the signalling of neurons.

A human astrocyte. Source: Wikipedia

Astrocytes provide nutrients and neurotrophic factors to neurons and make sure the environment surrounding the neurons is balanced and supportive. Glial cells are absolutely critical to the normal functioning of the brain.

What are neurotrophic factors?

Continue reading “TGF-beta: The Parkinson’s superfamily?”