The inflammasome field is heating up

 

When a cell is sick or damaged it will send out signals alerting the immune system that something is wrong. If enough of these molecules are released, they will initate an “immune response” and this process is called inflammation.

There is evidence in neurodegenerative conditions (like Parkinson’s and Alzheimer’s) that the inflammation process is involved, and inhibitors of particular aspects of inflammation are being developed as potential therapies for these conditions.

Of particular interest are drugs targeting the NLRP3 inflammasome.

In today’s post, we will discuss what the NLRP3 inflammasome is, look at new research identifying a novel NLRP3 inflammasome inhibitor, and provide an overview/update of where things are in the clinical testing of NLRP3 inflammasome inhibitors for Parkinson’s.

 

Source: Science

One of the hottest areas of Parkinson’s research world is ‘inflammation’ (cheesy pun intended).

What is inflammation?

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

When enough of these messenger proteins are released that the immune system becomes activated, it can cause inflammation.

Inflammation is a critical part of the immune system’s response to trouble. It is the body’s way of communicating to the immune system that something is wrong and activating it 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. And there are processes that can amplify the immune response.

One of those processes is called inflammasomes.

What are inflammasomes?

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The Tau of LRRK2

 

Dense spherical clusters of a protein – called Lewy bodies – are one of the classical hallmarks of the Parkinsonian brain. They are a common pathological feature, but curiously they are not present in all cases of Parkinson’s.

For example, some individuals with certain forms of Parkinson’s associated with specific genetic mutations do not exhibit any Lewy bodies. Variations in a region of DNA called LRRK2 will increase one’s risk of developing Parkinson’s, but many of those who go on to develop LRRK2-associated Parkinson’s will have a complete absence of Lewy bodies in their brains. These cases have represented an enigma for the Parkinson’s research community and have been difficult to reconcile.

Recently, however, researchers from the University of Pennsylvania have reported a different kind of protein clustering in these LRRK2-associated cases with “no Lewy bodies”. The accumulating protein is called Tau.

In today’s post, we will look at what Tau is, review what the new research report found, and discuss what this discovery could potentially mean for the future treatment of Parkinson’s.

 

Neuropathologists conducting a gross examination of a brain. Source: NBC

At present, a definitive diagnosis of Parkinson’s can only be made at the postmortem stage with an examination of the brain.

Until that moment, all cases of Parkinson’s are ‘suspected’. When a neuropathologist makes an examination of the brain of a person who passed away with the clinical features of Parkinson’s, there are two characteristic hallmarks that they will be looking for in order to provide a final diagnosis of the condition:

1.  The loss of specific populations of cells in the brain, such as the dopamine producing neurons in a region called the substantia nigra, which lies in an area called the midbrain (at the base of the brain/top of the brain stem). As the name suggests, the substantia nigra region is visible due to the production of a ‘substance dark’ molecule called neuromelanin in the dopamine neurons. And as you can see in the image below, the Parkinsonian brain has less dark pigmented cells in the substantia nigra region of the midbrain.

The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinsonian brain (right). Source:Memorangapp

2.  Dense, circular clusters (or aggregates) of protein within cells, which are called Lewy bodies.

shutterstock_227273575A cartoon of a neuron, with the Lewy body indicated within the cell body. Source: Alzheimer’s news

A Lewy body is referred to as a cellular inclusion, as they are almost always found inside the cell body. They generally measure between 5–25 microns in diameter (5 microns is 0.005 mm) and thus they are tiny. But when compared to the neuron within which they reside they are rather large (neurons usually measures 40-100 microns in diameter).

A photo of a Lewy body inside of a neuron. Source: Neuropathology-web

Do all Parkinson’s brains have Lewy bodies?

Funnily enough, no.

And this is where the wheels fall off the wagon in our understanding (and ‘definitive’ definition) of Parkinson’s.

What do you mean?

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Monthly Research Review – November 2019

 

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 November 2019.

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
  • Review articles/videos

 

So, what happened during November 2019?

In world news:

November 4th – Researchers reported that the spacecraft Voyager 2 has reached interstellar space, following Voyager 1’s historic passage six years ago.

November 7th – New Zealand wrote into law zero carbon immission the same day as Collins Dictionary announced that ‘Climate strike’ was the 2019 word of the year (Click here and here to read more about this).

November 18th – A new study suggests that Humpback whales in the South Atlantic have recovered from near-extinction. Counts show the population off Brazil has climbed from about 450 in the 1950s to 25,000 today (Click here to read more about this).

November 23rd – Max the dog put his owners car in reverse and…

 

November 27th – Researchers created strains of Escherichia coli bacteria that consume carbon dioxide for energy instead of organic compounds (Click here and here to read more about this).

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

In November 2019, there were 738 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (7538 for all of 2019 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 6 pieces of Parkinson’s news

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Making a strong case for GCase

Novel therapies are increasing being developed to focus on specific subtypes of Parkinson’s. The hope is that if they work on one type of Parkinson’s, then maybe they will also work on others.

Many of these new experimental treatments are focused on specific genetic subtypes of the condition, which involve having a specific genetic variation that increases one’s risk of developing Parkinson’s.

Increasing amounts of data, however, are accumulating that some of the biological pathways affected by these genetic variations, are also dysfunctional in people with sporadic (or idiopathic) Parkinson’s – where a genetic variation can not explain the abnormality.

In today’s post, we will review some new research that reports reductions in a specific Parkinson’s-associated biological pathway, and discuss what it could mean for future treatment of the Parkinson’s.

Source: Medium

I was recently at a conference on Parkinson’s research where a prominent scientist reminded the audience that just because a person with Parkinson’s carries certain genetic risk factor (an error in a region of their DNA that increases their risk of developing Parkinson’s), does not mean that their Parkinson’s is attributable that genetic variation. Indeed, lots of people in the general population carry Parkinson’s associated genetic risk factors, but never go on to develop the condition.

And this is a really important idea for the Parkinson’s community to understand: Most of the genetics of Parkinson’s deals with ‘association’, not with ‘causation’.

But that begs the question ‘if we do not know that these errors in our DNA are causing Parkinson’s, then why should we be trying to develop therapies based on their biology?’

It is a fair question (it is also a very deep and probing question to start a post off with!).

The genetics of Parkinson’s has been extremely instructive in providing us with insights into the potential underlying biology of the condition. We have learnt a great deal about what many of the biological processess thatare associated with these genetic risk factors, and (yes) various experimental therapies have been developed to target them.

These novel treatments are clinically tested in the hope that they will have beneficial effects not just on individuals carrying certain genetic risk factors, but also on the wider Parkinson’s community.

And recently, there has been increasing evidence supporting this possibility. Some of the biological pathways associated with these genetic mutations appear to also be abnormal in people with Parkinson’s who do not carry the genetic variation.

What do you mean?

Continue reading →

AMP-PD is here

 

Today the US National Institute of Health (NIH) announced the opening of the data portal for the Accelerating Medicines Partnership for Parkinson’s disease (or AMP-PD) initiative.

This research program is a MASSIVE collaborative effort between the NIH, multiple biopharmaceutical/life sciences companies, and non-profit organisations.

It involves a pooling together of “well characterized cohorts with existing biosamples and clinical data”, and making this data available for researchers in order to identify and validate diagnostic, prognostic, and progression biomarkers.

In today’s post, we will look at what the AMP-PD initiative is, and consider how it could help to accelerate the development of novel therapies for Parkinson’s.

 

The US National Institute of Health Clinical Research Center, Bethesda, Maryland. Source: Wikipedia

In the late 1870s, the US ongress allocated funding for the investigation of the causes of specific epidemics (such as cholera and yellow fever). An urgent need was recognised and the US congress acted.

In doing so, however, it not only created the National Board of Health, but it also made medical research an official government initiative.

The National Board of Health was re-designated several times and in 1930 the US National Institutes of Health (or NIH) was born.

The NIH has gone on to become one of the largest funders of medical research in the world. And some of the numbers are really staggering (Source):

  • The NIH invests nearly $39.2 billion annually in medical research
  • More than 80% of the NIH’s funding is awarded to over 50,000 competitive grants.
  • These grants fund 300,000 researchers at more than 2,500 universities/research institutions in every US state and around the world.
  • About 10% of the NIH’s budget supports projects conducted by nearly 6,000 scientists in its own laboratories

It is an institution that can seriously change the landscape for medical research. And recently it has been trying to do this via AMP programmes.

What are AMP programmes?

Continue reading →

Distinctly human: Kangaroos

 

It is often said that only humans develop Parkinson’s. It is a distinctly human condiiton, and this is true (at the time of publishing this post).

But there are interesting Parkinson’s-related observations in the animal world that could tell us something about this ‘very human’ condition. We have previously highlighted reports of this nature (Click here for an example).

Recently Australian researchers have reported the accumulation of the Parkinson’s-associated protein alpha synuclein in the brains of kangaroos, after they ate a particular type of grass (phalaris pastures plants) which is toxic for them.

In today’s (short) post, we will discuss what the report found, look at what the plants contains, and consider what this could mean for our understanding of Parkinson’s.

 

Source: SanDiegoZoo

The first interesting fact about kangaroos in today’s post: They are predominantly left handed

What?!?!?

Researchers published a study in 2015 reporting that while most four legged marsupials show no preference between their limbs, kangaroos are very left handedness (Click here to read the report)

Source: Cell

This finding is interesting as it could tell use much about our own handedness preference (Click here to read more about this).

Ok, interesting. But what on Earth does this have to do with Parkinson’s?

Ah, well that’s where we come to the second interesting fact about kangaroos in today’s post:

Continue reading →

There’s gold in them tha brains

 

It feels as though novel potential therapies for Parkinson’s are being proposed with an ever increasing frequency. And just when I think there must be few other ways of attacking the condition, a new method is proposed. Recently a biotech firm called Clene Nanomedicine presented data on one such new approach.

The experimental treatment is called CNM-Au8 and it involves gold. Yes, that gold.

And the treatment is already being tested in a clinical trial for Parkinson’s.

In today’s post, we will look at what CNM-Au8 is and what it does, we’ll discuss what data has been presented, and then we’ll outline what the clinical trial involves.

 

Source: SFN

Although I did not attend the Society for Neuroscience 2019 annual meeting in Chicago in October, I have still had a look at some of the 816 abstracts which had the keyword “Parkinson’s” attached to them (my Saturday night entertainment – sad I know!).

Those abstracts can be found online (Click here to search those abstracts).

One in particular abstract caught my attention:

This poster was presented by research scientists from a biotech company that I had never heard of called Clene Nanomedicine:

And the data presented focused on a novel therapy that I had never heard of which is now being targetted at Parkinson’s.

The new treatment is called CNM-Au8.

What is CNM-Au8?

Continue reading →

Shining a light on Parkinson’s

 

NOTE: The information in today’s post should not be considered an endorsement of PhotoPharmics or the treatment they are proposing. The author of this blog has had no communication with the company. The information in this post is provided because the author has been asked by readers to discuss it.

In October 2018, at the annual International Movement Disorders Society meeting in Hong Kong, a small biotech firm called “PhotoPharmic” presented a poster entitled “Double-blind controlled trial of Spectramax™ light therapy for the treatment of Parkinson’s disease patients on stable dopaminergic therapy.”

In the poster provided the results of a study in which 45 participants with Parkinson’s were blindly treated with light therapy for 1 hour each evening over the course of 6 months. At the end of the study, the investigators found clinically meaningful improvements in the MDS-UPSDRS rating scale, as well as significant improvements in non-motor measures.

In today’s post, we will discuss what light therapy is, what this study found, and look at what PhotoPharmic plan to do next.

 

The Tasmanian “light bucket” for Parkinson’s. Source: ABC

It might come as a bit of a surprise to some readers, but one of my favourite stories of 2019 from the world of Parkinson’s research originates from Tasmania.

It is a tale that involves a group of Australian Parkinson’s advocates who somehow cottened on to a seemingly inconceivable idea (treating oneself with a homemade light bucket). But their project was embraced by the local Tasmanian community which is helping out with the research, for example the Dorset community men’s shed is helping to make the light buckets.

The Dorset community men’s shed helps to make the buckets. Source: ABC

And whatsmore they have inspired an Australia-wide “proof-of-concept” clinical trial on the topic.

The trial is being conducted by The University of Sydney School of Medicine and Parkinson’s South Australia. There is also a website where you can follow the various activities surrounding the trial – Click here to see the website.

Designing the helmet for the Sydney clinical trials. Source: ABC

And there is already published research coming out of the clinical study:

Title: “Buckets”: Early Observations on the Use of Red and Infrared Light Helmets in Parkinson’s Disease Patients.
Authors: Hamilton CL, El Khoury H, Hamilton D, Nicklason F, Mitrofanis J.
Journal: Photobiomodul Photomed Laser Surg. 2019 Oct;37(10):615-622.
PMID: 31536464

Now to be clear, I do fully not understand the biology behind the idea, and it would be easy for me to make fun of this whole situation. But I really do love this story. The ivory towers of industry and academic research may scoff at such a story, but I hope that this study will lead to something new and wonderful (the way Joy Milne’s “smell of Parkinson’s” has opened new areas of research – click here to read a previous SoPD post about that).

The light bucket “photobiomodulation” clinical trial for Parkinson’s is a great story about the DIY attitude, community sharing/helping, curiosity & some serious left field thinking ( to read a prominent newspaper story about this).

Photobiomodulation? Are you serious? How on Earth can LIGHT help with Parkinson’s?

Continue reading →

The Neuraly trial

 

 

 

This week a new clinical trial was registered which caught our attention here at the SoPD HQ. It is being sponsored by a small biotech called Neuraly and involves a drug called NLY01.

NLY01 is a GLP-1R agonist – that is a molecule that binds to the Glucagon-like peptide-1 receptor and activates it. Other GLP-1R agonists include Exenatide (also called Bydureon) which is also also about to start a Phase III clinical trial in Parkinson’s (Click here to read a previous SoPD post about this).

There is a lot of activity in the Parkinson’s research world on GLP-1R agonists at the moment.

In today’s post, we will discuss what a GLP-1R agonist is, what we know about NLY01, and what the new clinical trial involves.

 

 

Every week there are new clinical studies being announced for Parkinson’s.

Many of them are registered on the Clinicaltrials.gov website. Here at the SoPD, we try to keep track of new trials being registered (the SoPD Twitter account highlights the more interesting trials).

This week one particular newly registered clinical trial stood out. It involves a small biotech company Neuraly (which is owned by parent company D&D PharmaTech).

And the drug being tested in the Neuraly clinical trial is a GLP-1R agonist.

What is a GLP-1R agonist?

Continue reading →

Improving the SoPD blog – any thoughts?

 

Here at the SoPD, we are always seeking feedback from readers to provide better content and more relevant information.

Today’s post is a request for feedback – an exercise in self improvement.

 

Source: Medium

If I have any philosphy in life it is wabi-sabi (侘寂).

In traditional Japanese aesthetics, wabi sabi is a world view centered on appreciating the beauty of impermanence, imperfection, and incompleteness.

Autumn – very wabi sabi. Source: Shelburnemuseum

That said, I see no problem with trying to improve things. And following that line of thought, today’s post is a request for help to make the SoPD less imperfect and less incomplete.

It is very easy in science to get very exciting about the details and fail to see the big picture (a ‘not seeing the forest for the trees’ scenario). Most researchers fall down the rabbit hole of their area of interest and become obsessed with the minutiae. This situation on a science blog, however, can make one blind to what the reader may actually be looking for. Similarly, I have certain ideas about how this blog is developing and where it could be going which may not be the best way to serve the Parkinson’s community.

So in this post, we will review where things on the SoPD currently stand, before then inviting your feedback.

The state of the blog:

Continue reading →