CMT-3: A better option than doxy?

# # # #

It has been reported by multiple independent research groups that tetracycline-based antibiotic drugs (such as doxycycline) have exhibited neuroprotective properties in models of Parkinson’s.

Translation of these preclinical findings into the clinic has, however, been difficult. In addition, concerns have been expressed that long-term use of such agents could bring forward the emergence of antibiotic resistance in the bacteria that they are used to control.

Recently, researchers have investigated a different type of tetracycline-based molecule that has reduced antibiotic activity, crosses the blood-brain-barrier, and is pharmacologically safe. It is called chemically modified tetracycline 3 (or CMT-3).

In today’s post, we will look at the research that has been done on tetracycline-based antibiotic drugs, discuss why we should not be testing antibiotics in Parkinson’s, and consider if CMT-3 could be different.

# # # #


image-title1

Sir Alexander Fleming. Source: Biography

Sir Alexander Fleming is credited with discovering the antibiotic properties of penicillin.

But – as he himself notes – the discovery was a purely chance event. An accident, if you like.

After returning from a two week holiday, Sir Fleming noticed that many of his culture dishes were contaminated with fungus, because he had not stored them properly before leaving. One mould in particular caught his attention, however, as it was growing on a culture plate with the bacteria staphylococcus. Upon closer examination, Fleming noticed that the contaminating fungus prevented the growth of staphylococci.

In an article that Fleming subsequently published in the British Journal of Experimental Pathology in 1929, he wrote, “The staphylococcus colonies became transparent and were obviously undergoing lysis … the broth in which the mould had been grown at room temperature for one to two weeks had acquired marked inhibitory, bactericidal and bacteriolytic properties to many of the more common pathogenic bacteria.

photograph_from_1929_paper_by_fleming

Penicillin in a culture dish of staphylococci. Source: NCBI

Fleming isolated the organism responsible for prohibiting the growth of the staphylococcus, and identified it as being from the penicillium genus.

He named it penicillin and the rest is history (Click here to read that history).

Fleming himself appreciated the serendipity of the finding:

When I woke up just after dawn on Sept. 28, 1928, I certainly didn’t plan to revolutionise all medicine by discovering the world’s first antibiotic, or bacteria killer” (Source)

And this gave rise to his famous quote:

“One sometimes finds what one is not looking for” (Source)

While Fleming’s discovery of the antibiotic properties of penicillin was made as he was working on a completely different research problem, the important thing to note is that the discovery was made because the evidence came to a prepared mind.

Louis-Pasteur-Quotes-1

Pasteur knew the importance of a prepared mind. Source: Thequotes

And this is the purpose of all the training in scientific research – not acquiring the keys to some special knowledge, but preparing the investigator to notice the curious deviation.

That’s really interesting, but what does any of this have to do with Parkinson’s?

Continue reading “CMT-3: A better option than doxy?”

ALS: From ice bucket to centaur

# # # #

Amyotrophic lateral sclerosis (or ALS) is the third most common neurodegenerative condition. It is characterised by the loss of motor neurons, which leads to loss of muscle control.

As with Parkinson’s, there is no cure for ALS, and there are only two FDA approved therapies for the condition.

Recently, a biotech company – called Amylyx Pharmaceuticals announced positive Phase II clinical trial results with their experimental combination therapy AMX0035.

In today’s post, we will discuss what ALS is, explore the results of the AMX0035 trial, and consider why this could be an important development for Parkinson’s as well.

# # # #


lou-gehrig

Lou Gehrig. Source: NBC

In 1969, Henry Louis “Lou” Gehrig was voted the greatest first baseman of all time by the Baseball Writers’ Association. During his career, he played 17 seasons with the New York Yankees, having signed with his hometown team in 1923.

For 56 years, he held the record for the most consecutive games played (2,130), and he was only prevented from continuing that streak when he voluntarily took himself out of the team lineup on the 2nd May, 1939, after his ability to play became hampered.

A little more than a month later (at age 36) he retired from the game – his farewell being capped off by his iconic “Luckiest man on the face of the Earth” speech:

And sadly, less than two years later he passed away from the disease that now bears his name: Lou Gehrig’s disease.

Or as it is more commonly known as motor neuron disease.

What exactly is motor neuron disease?

Continue reading “ALS: From ice bucket to centaur”

Yo DJ, stop mis-splicing

# # # #

RNA – the usable copy of a section of DNA – has regions called introns that need to be removed before the RNA can be used for the production of protein. The process of removing introns is called splicing.

Recently researchers have noticed that a genetic mutation in a Parkinson’s-associated gene – called DJ-1 – affects the splicing of the associated RNA and this has serious consequences on the activity of the DJ-1 protein.

Interestingly, they were able to pharmacologically rescue the effect, and noticed that DJ-1 might not be the only Parkinson’s-associated gene affected by this splicing error.

In today’s post, we will discuss what splicing is, review the new research, and discuss the wider implications for the Parkinson’s community.

# # # #


Source: Wikibooks

Today’s post starts off with a definition:

Splice/splʌɪs/; verb;
Meaning: “to combine, interweave”.
Origin: 16th century: probably from Middle Dutchsplissen,
Similar:  braid, plait, entwine, intertwine, interlace, knit
Additional/alternative meanings:
1.  (From the arts) When two pieces of recorded music – with a similar key and tempo – are combined:

2.  (From biology) The process that removes the intervening, non-coding sequences of genes (introns) from pre-mRNA and joins the protein-coding sequences (exons) together in order to enable translation of mRNA into a protein:

Ok, so the first alternative definition about music I understood and the video was helpful, but can you explain the second definition in more detail please?

Continue reading “Yo DJ, stop mis-splicing”

Administrative post: Approaching 500

# # # #

A week or so ago, I was poking around in the cluttered back room of this website when I found something that truly stunned me: The SoPD website had 468 posts (This post is #470)

For a moment I was speechess. And as I looked at the number, a mix of horror and awe passed over me. If I had to have a guess, I would have said there were perhaps 300 or so posts on the website, but definitely not 500. That’s a ridiculous number!

Having given it some thought, a round number like 500 deserves something special.

Today’s post is a request to readers for ideas on how to mark the occasion.

# # # #


Beau Miles. Source: Youtube

The guy in the image above is Beau MilesUniversity lecturer, filmaker, adventurer, “poly-jobist”.

When I need a break and I want something off beat, Beau’s Youtube channel is my usual first port of call. If you have never heard of him, I would recommend starting off gently with his Run the line video and then diving head first into the madness that is A mile an hour.

Beau is one of those “exploring the human experience” types and he films himself doing it. He’s a great story teller and his quirky adventures are always good viewing – like the time Steinbeck inspired him to eat his own body weigh in canned beans. Just beans. It took him 40 days (Click here for that video).

Source: Hedonistica

What does this have to do with Parkinson’s?

Continue reading “Administrative post: Approaching 500”

Ending Par(aquat)-kinson’s

# # # #

Today’s post is an open letter to Jacinda Ardern – Prime minister of New Zealand.

# # # #

Dear Jacinda (if I may),

Firstly, let me thank you for your actions during your first term as Prime Minister of New Zealand. The empathy and compassion you expressed in the face of tragic events like Christchurch and White Island have been exemplary, and the stewardship that you have demonstrated on COVID-19 has been a template for the rest of the world to follow. Even though I have lived away from NZ for almost 20 years now, the example you present makes one proud to be a kiwi. And congratulations on winning another term in the recent elections – Godspeed.

The reason for my letter today is to bring your attention to a matter that should be addressed by your Government: a complete ban on the continued use of the non-selective chemical herbicide, paraquat.

Continue reading “Ending Par(aquat)-kinson’s”

T-cells: First responders

# # # #

The cause of the cell loss and pathology associated with Parkinson’s is still unknown. While the later stages of the condition have been well investigated based on various pathological marker (ie Braak staging), the early manifestations of the condition are still a mystery.

Cells of the immune system are early responders to any signs of trouble in our bodies, and recently researchers have been looking at a specific class of immune cells (called T cells) in postmortem sections of brains from people who passed away with Parkinson’s.

Curiously, in their analysis the researchers found that the bulk of activity of T cells occurs before any cell loss or pathology appears.

In today’s post, we will discuss what T cells are, review the new research, and explore what this could mean for potential therapies for Parkinson’s.

# # # #


Your hematopoietic system. Source: Wikipedia

The process of hematopoiesis (or blood formation) is absolutely fascinating.

Seriously.

You start off with a single, multi-potential hematopoietic stem cell. This is called a hemocytoblast (it’s the big cell in middle of the image below):

A hemocytoblast. Source: Pinterest

Given enough time, this single cell will give rise to an entire blood system, made up of many of different types of cells with very specific functions that are required for us to live normal lives.

It is a remarkable achievement of biology.

Understand that at any moment in time your blood system will contain 20-30 trillion cells (in the average human body). And as the image near the top of the post suggests, there are quite a few branches of potential cell types that these blood stem cells can generate.

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

Continue reading “T-cells: First responders”

Monthly research review – October 2020

# # # #

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 October 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 October 2020?

In world news:

October 7th – Emmanuelle Charpentier and Jennifer Doudna won the 2020 Nobel Prize for Chemistry “for the development of a method for genome editing” (aka CRISPR technology – Click here to read more about this).

October 12th – One of the winners of the 2020 Nobel Prize in economics, Paul Milgrom found out that he had won when his neighbour came knocking on his door at 2am (Click here to read more about this):

 

15th October – the John Snow Memorandum was announced in the medical journal The Lancet, providing a current evidence-based consensus on COVID-19 and partly in response to the many assumptions made in the Great Barrington declaration”.

18th October – Birdwatchers flocked to a salt marsh in the East of England to see a rufous bush chat – a bird that has not been seen in Britain for 40 years (Click here to read more about this).

29th October – NASA’s “Origins, Spectral Interpretation, Resource Identification, Security, Regolith Explorer” (OSIRIS-REx) mission successfully landed for a few seconds on an asteroid and collected a rock for return to Earth – all more than 205 million miles (330 million km) from Earth (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 October 2020, there were 957 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (8926 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 – October 2020”

Is there something in the air?

# # # #

Air pollution is an international problem in the post-industrial world. Poor air quality has been associated with an increasing number of medical conditions.

For a long time there has been indications that neurodegenerative conditions – such as Parkinson’s and Alzheimer’s – could also be associated with air pollution.

Recently, several research reports have been published providing compelling evidence further supporting the association and raising new questions. 

In today’s post, we will review some of that research and discuss what could be done next (SPOILER ALERT: the solution involves needing cleaner air).

# # # #


Vast. Source: Unequal

I have been extremely fortunate in my life to have travelled to a few of the major cities of the world, but none have had as much impact on me upon arrival as Mexico city.

The pilot had announced over the loud speaker that we were approaching the outskirts of the city, and I looked out of my window to catch a first glimpse of the central American metapolis. Block after block of dwellings passed beneath us, and I thought “great, we’ll be landing soon“.

Mexico City: Really vast. Source: lsecities

Three minutes later, block after block of dwellings were still passing beneath us.

It was the first really vast city that I had ever visited.

Covering approximately 1,500 square kilometers (580 sq miles) of an old volcanic crater, the city is huge. By comparison, New York city covers only 1/2 the area (approximately 780 square kilometers or 300 sq miles – Source).

Home to over 8 million people, Mexico city was an amazing place to explore.

Palacio de Bellas Artes. Source: Turkishairlines

The art, the culture, the history, and the food – lots to see and experience!

Bosque de Chapultepec. Source: Jetsetter

But like all big cities, Mexico city has its share of problems. In addtion to sinking more than 10 metres over the past century (Click here to read more about this), Mexico City also has a terrible air population problem.

And this latter issue has recently been implicated in some Parkinson’s related research.

What do you mean?

Continue reading “Is there something in the air?”

When Inflazome becomes Roche

# # # #

Over the past two decades, pharmaceutical companies have shifted from maintaining large in-house drug development platforms to a model that involves acquiring small biotech firms with interesting agents once those companies reach a certain point in their maturation.

This week a biotech firm called Inflazome was bought by the big pharma Roche.

Inflazome has been developing a novel NLRP3 inhibitor, which targets inflammasome activation and the company has had Parkinson’s in it’s sights as far as indications of interest.

In today’s post, we will discuss what the inflammasome is, how NLRP3 inhibitors work, and what will be happening next.

# # # #


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?

Continue reading “When Inflazome becomes Roche”

Further support for GLP-1R agonists

# # # #

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.

# # # #


static1.squarespace

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

rudw9esurtnukjwruf7q

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 TsienDavid 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”