Further support for GLP-1R agonists

~ Simon ~ 6 Comments

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Glucagon-like peptide 1 receptor (or GLP-1R) agonists are a frontline treatment for diabetes – improving glycaemic control by reducing glucose concentrations in the blood.

In 2008, multiple research groups reported that this class of drugs exhibited neuroprotective properties in models of Parkinson’s. Subsequent clinical trials have provided encouraging data supporting this assertion.

Recently, researchers have found further support for potential beneficial effects in a large epidemiological study.

In today’s post, we will discuss what GLP-1R agonists are, what has previously been done with them in Parkinson’s, and what the new report found.

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In 2012, the Golden Goose Award was awarded to Dr John Eng, an endocrinologist from the Bronx VA Hospital.

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Dr John Eng. Source: Health.USnews

The Award was originally created in 2012 to celebrate researchers whose seemingly odd or obscure federally funded research turned out to have a significant and positive impact on society.

And despite the name, it is a very serious award – past Nobel prize winners (such as Roger Tsien, David H. Hubel, and Torsten N. Wiesel) are among the awardees.

Sounds interesting. What did Dr Eng do?

Continue reading “Further support for GLP-1R agonists” →

A PINK shade of inflammation

~ Simon ~ 5 Comments

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Inflammation is the means by which tissue in our bodies communicate with the immune system to indicate when something is wrong. Tiny messenger proteins are released from stressed or damaged cells to alert neighbouring cells of their situation.

Ailing cells can also release additional components – such as DNA – that can activate immune cells and cause inflamation.

Recently, researchers have identified both messenger proteins and specific types of DNA that are present in the blood of individuals with a genetically-associated sub-type of Parkinson’s. The discovery could provide both novel biomarkers, but also point towards specific biological pathways that could be therapeutically targetted.

In today’s post, we will review this new research.

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Ouch! Source: MedicalExpress

When cells in your body are stressed, damaged, or sick, they begin to release large amounts of tiny messenger proteins which inform the rest of your body that something is wrong.

When enough of these messenger proteins are released, cells of the immune system will become activated, and come looking for the source of the trouble.

This is inflammation.

Source: Youtube

Inflammation is a critical part of the immune system’s response to problems. It is the body’s way of communicating with the immune system and explaining that something is wrong. This also aid in activating the immune system so that it can help deal with the situation.

By releasing the messenger proteins (called cytokines), injured/sick cells kick off a process that results in multiple types of immune cells entering the troubled area of the body and undertaking very specific tasks.

The inflammatory process. Source: Trainingcor

The strength of the immune response depends on the volume of the signal arising from those released messenger proteins.

For a long time, it has been hoped that some of these messenger proteins might be useful as biomarkers for conditions like Parkinson’s. And recently, researchers have published data suggesting that they might have found one cytokine that could be very useful for a specific sub-set of people with Parkinson’s.

What did they find?

Continue reading “A PINK shade of inflammation” →

The world according to GARP

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Transportation of material inside of cells is a critical aspect of normal cellular functioning. Any disruption to this activity can cause significant problems.

An interesting aspect of recent genetic analysis work in Parkinson’s has been the number of genetic risk factors for the condition that are associated with cellular transportation activity.

Recently, researchers have discovered that one particular Parkinson’s-associated protein – LRRK2 – interacts with a cellular transport protein complex called GARP.

In today’s post, we will discuss what LRRK2 and GARP do and why their interaction is important.

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John Irving. Source: Achievement

John Irving is not everyone’s cup of tea, but I quite like his books (A Prayer for Owen Meany being my favourite).

In his fourth book (The World According to Garp), Irving wrote about about the life of T. S. Garp. Born out of wedlock to a feminist leader, Garp grows up to be a struggling writer and freestyle wrestler. But it is his interactions with his wife and his mother’s friends & acquaintances that really make Garp’s unusual life a good read.

A young Robin Williams played Garp in the 1982 film adaptation of the book:

But what does this have to do with Parkinson’s?

Well, recently in the field of Parkinson’s research, the interactions of different kind of GARP have made for good reading.

What do you mean?

Continue reading “The world according to GARP” →

The 2020 Linked Clinical Trials meeting

~ Simon ~ 11 Comments

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Each year in September, The Cure Parkinson’s Trust and Van Andel Institute hold the international Linked Clinical Trials (iLCT) meeting.

This is a drug-repurposing initiative focused on disease modification in Parkinson’s. For two days the iLCT committee discuss and debate the virtues of 20+ molecules to decide which should be prioritised for clinical evaluation. 

Due to the current COVID-19 situation, the 2020 iLCT meeting was held virtually.

In today’s post, we will discuss what the iLCT program is and provide an overview of what happened at the 2020 meeting.

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The top line results of the PD-STAT clinical trial evaluating the cholesterol-reducing drug simvastatin in Parkinson’s were recently announced (Click here to read more about this). Preclinical data had suggested that this agent displayed neuroprotective properties in models of Parkinson’s, and given its long history of clinical use and agreeable safety profile, simvastatin seemed like an ideal candidate for repurposing to Parkinson’s.

A large Phase II clinical trial was set up and conducted across nation-wide network of 23 hospitals in the UK. It recruited over 230 brave individuals to be treated with the drug for 2 years and undergo regular clinical assessments.

The results of the study found that the treatment has had no impact on slowing the progression of Parkinson’s (Click here to read more about this).

That’s disappointing. What happens next?

Disappointing as the result is, the findings of the study provide us with a definitive answer, allowing us to move forward with testing other drugs of interest.

Simvastatin was a drug that was prioritised by the international Linked Clinical Trials programme, and while this agent might not have shown any beneficial efforts in Parkinson’s the good news is that there are lots of other drugs that have been prioritised by the international Linked Clinical Trials programme and they are now being clinically tested.

What is the international Linked Clinical Trials programme?

Continue reading “The 2020 Linked Clinical Trials meeting” →

Monthly Research Review – September 2020

~ Simon ~ 2 Comments

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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 September 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
  • Other news
  • Upcoming conferences/lectures
  • Review articles/videos

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So, what happened during September 2020?

In world news:

September 2nd – Researchers found a way of floating toy boats under a levitating liquid (Click here to read more about this and click here to read a press summary)

September 3rd – The skeletons of 200 mammoths and 30 other animals are unearthed at a construction site for the Mexico City Santa Lucía Airport. It is the largest find of mammoth bones to date, surpassing the Mammoth Site in the U.S. which had 61 skeletons (Click here to read more about this).

September 14th – The Royal Astronomical Society announces the detection of phosphine in Venus’ atmosphere, which is suggested to be a strong predictor for the presence of microbial life (Click here to read more about this).

September 19th – A 1634 edition of The Two Noble Kinsmen, the last play by English playwright William Shakespeare, is discovered at the Royal Scots College’s library in Salamanca, Spain. It is believed to be one of the oldest copies of any of his works.

September 25th – Researchers report the development of rectangular, magnetically controlled robots (300 micrometers long) that can coax nerve cells to grow new connections (Click here to read more about this and click here to read a press summary)

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

In September 2020, there were 1,021 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (7,969 for all of 2020 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 – September 2020” →

Problems with PARKIN in PARIS

~ Simon ~ 1 Comment

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PARKIN is a protein that is associated with a young-onset form of Parkinson’s. Individuals carrying tiny genetic variants in the region of DNA producing this protein have a higher risk of developing Parkinson’s before the age of 40 than non-carriers.

The PARKIN protein is believed to play an important role in the disposal of old/damaged mitochondria (the power stations of cells). But recent research points towards another protein – that interacts with PARKIN – which may also be implicated in the health and well being of mitochondria.

That other protein is called PARIS.

In today’s post, we will discuss what PARKIN does, explore how PARIS could be involved, and reflect on what this could mean for future therapies targeting PARKIN-associated Parkinson’s.

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paris

No label required. A magnificent city. Source: HathawaysofHaworth

Paris is not my favourite city (Hanoi takes that spot), but it is probably in the top 10.

Like London and New York, La Ville Lumière is an incredible place to be fortunate enough to visit.

If you ever find yourself in Paris, bored of all the art, culture, food, etc, and you feel like something more scientific, make your way up the Seine river to the 5th arrondissement, and try to find the Muséum national d’histoire naturelle. Once you get there, ask for the “Galerie de Paléontologie et d’Anatomie comparée” (Paleontology and comparative Anatomy Gallery):

This is the realm of Georges Cuvier – the French paleontologist who researched fossils and in 1796 laid out the first ideas for extinction theory. It is a hall of scientific wonder.

As I say, it is worth a visit if ever you are bored in Paris. But be warned that parking is an issue at the Jardin des plantes where the gallery is located.

In fact, parking is an issue everywhere in Paris.

It seems like Parking and Paris do not mix.

I’m sorry, but what does this have to do with Parkinson’s?

Continue reading “Problems with PARKIN in PARIS” →

$161 million over three years

~ Simon ~ 7 Comments

 

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The Aligning Science Across Parkinson’s (or ASAP) initiative is a major new source of funding for Parkinson’s research. And I mean MAJOR!

It is a global basic research initiative focused on fostering collaboration and resources to better understand the underlying causes of Parkinson’s. A return to basics in order to get a better grip on the biology of the disease.

Recently, the initiative announced their first round of grant awardees – handing out US$161 million for 3 year projects. This is one of the largest single rounds of research funding for Parkinson’s research ever!

In today’s post, we will look at what ASAP is, what the awarded projects will be investigating, and what this means for Parkinson’s research.

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NIH Parkinson’s research funding. Source: NIH

In 2016, the US National Institutes of Health (NIH – the world’s largest funder of medical research) allocated $161 million to Parkinson’s research.

It was a small fraction of the $30+ billion spent by the NIH on medical research that year, but it was still a much needed amount of money invested into research on this neurodegenerative condition.

This week, a major new Parkinson’s research program – called Aligning Science Across Parkinson’s (or ASAP – click here to read a previous SoPD post on this initiative) – announced the rewarding of $161 million in research funding to 21 projects involving 96 research leaders from 60 institutions across 11 countries (and 31 of the research leaders are female). Importantly, all of them are seeking to “accelerate targeted basic research and move us toward more meaningful advancements for Parkinson’s” (Click here to read the annoucement).

Think about that for a second:

ASAP has basically just allocated the same amount of funding to Parkinson’s research as the entire US Government did in 2016.

Wow!

Continue reading “$161 million over three years” →

The PASADENA study announcement (part 2)

~ Simon ~ 8 Comments

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In April of this year it was announced that the closely watched Phase II PASADENA clinical trial had not to met its primary objective. This was a large clinical evaluation of an immunotherapy approach (called prasinezumab) for disease modification in Parkinson’s. 

At the time of the announcement, it was indicated that the researchers who conducted the study had seen “signals of efficacy” in the data.

This week the results of the study were presented at an international conference and it was reported that prasinezumab “significantly reduced decline in motor function by 35% (pooled dose levels) vs. placebo after one year of treatment“.

In today’s post, we will discuss what the PASADENA study was, review the results that have been released, and discuss what might happen next.

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At 7am (just prior to the opening of the Swiss Stock Exchange) on Wednesday 22nd April 2020, the pharmaceutical company Roche published its sales results for the 1st Quarter. The financial report looked good, particularly considering the current COVID-19 economic climate, but there was one sentence on page 133 of the results (highlighted below) that grabbed a lot of attention:

From page 133. Source: Roche

For those of you (like myself) who struggle with fine print, the sentence reads:

“Study did not meet its primary objective, but showed signals of efficacy“

This was how the Parkinson’s community found out about the top line result of the closely followed Phase II PASADENA study evaluating the immunotherapy treatment prasinezumab in individuals recently diagnosed with Parkinson’s.

Many within the Parkinson’s community were basically:

Yet another negative clinical trial result.

But then, later that same day, the biotech firm Prothena – which developed prasinezumab and is partnered with Roche in the clinical testing – kindly provided a press release.

And in that document, the company repeated that prasinezumab “showed signals of efficacy” , but importantly: “These signals were observed on multiple prespecified secondary and exploratory clinical endpoints“.

And then the Parkinson’s community was like:

This week we found out more about those “signals of efficacy” and the results of the PASADENA study, and they look interesting.

What do the results show?

Continue reading “The PASADENA study announcement (part 2)” →

CPTX: Gluing the brain back together

~ Simon ~ 1 Comment

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Current clinical efforts at restorative medicine for neurodegeneration are still largely focused on stem cell and neurotrophic factor-based methods. Novel techniques are being preclinically proposed however, and some of them employ some radically different approaches.

An international group of researchers have recently published a report describing a means of repairing the damaged central nervous system that involves ‘gluing’ neurons together via an artificial protein.

They called this new method CPTX.

In today’s post, we will explore what this artificial protein does, what was reported in the new study, and consider how this could potentially be used for Parkinson’s.

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Source: Howtogeek

Earlier in the year I wrote a post called the 2020 wish list, where I discussed some hopes for Parkinson’s research this year. Despite everything that 2020 (annus horribilis) has thrown at us, there have been significant developments regarding Parkinson’s research and some of those wishes.

One of those hopes was the announcement of new and innovative methods for restorative techniques for Parkinson’s. At present, all of the restorative approaches in clinical trial for Parkinson’s are focused on stem cell transplantation (Click here to read a recent SoPD post describing an example of this), and it would be good to broaden the range of approaches being tested.

As a result of this particular wish, a theme here on the SoPD this year has been to write posts highlighting new restorative research as it has been published (Click here, here and here to read some examples).

In today’s post, we are going to continue that theme with an extremely radical bit of research that utterly boggled my mind.

Me after reading this report. Source: 1zoom

Be warned, this is very futuristic, blue sky, “way out there on the horizon”-kind of stuff.

But when I read this report in August, I was left stunned… and rather excited by the potential possibilities.

Sounds interesting, what was the research report about?

Continue reading “CPTX: Gluing the brain back together” →

A tête-à-tête about TET2

~ Simon ~ 3 Comments

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Epigenetics is the study of how non-genetic factors affect genetics. It explores the influence of lifestyle or environmental factors on the activity surrounding our DNA.

Recently researchers have been investigating epigenetics within the context of Parkinson’s, and they have discovered a “master switch” that could represent an important target for future therapeutic treatments for the condition.

The research focuses on a protein called TET2.

In today’s post, we will discuss what epigenetics means, review the new research, and consider what the implications of these new findings could be.

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Not the same. Source: AutismBlog.

Identifical twin studies have been extremely useful to our understanding of conditions like Parkinson’s (Click here to read a previous SoPD post on twins research in Parkinson’s)

But the funny thing about identical twins is that in 100% of cases they aren’t identical.

Yeah sure, they initially share exactly the same DNA, but the further they get away from that magically moment of conception, the less alike they are.

Same DNA, subtle differences. Source: National Geographic

And we’re not talking about personality or likes/dislikes here.

As biological organisms twins diverge significantly after conception and as the age through life. But if they share the same DNA – the same genetic blueprint – how are these difference possible?

The answer to this question may lie in epigenetics.

What is epigenetics?

Continue reading “A tête-à-tête about TET2” →