Does Parkinson’s have us by the short and curli?

# # # #

For a some time, issues with the gastrointestinal system has been associated with Parkinson’s. For example, gut-related complaints – such as constipation and irritable bowel syndrome – are believed to be risk factors for developing the condition.

Researchers have recently been exploring the bacteria that inhabit the gastrointestinal system in the hope of identifying species of microbes that could be directly influencing the condition. Exactly how these tiny organisms might be doing that, however, remains a mystery.

Now researchers have focused their attention on a particular type of protein that is being produced by some of those bacteria. It is called curli.

In today’s post, we will discuss what curli is, explore what functions it has, and do a deep dive into some of the data suggesting it could be involved with Parkinson’s.

# # # #


Me. In a skirt. Eating dirt. Not my worst moment. Source: Drqaisrani

It has to be said that our gastrointestinal systems are incredibly robust.

When I think of all the rubbish I put down my throat as a toddler (and then of all the rubbish I put into my gut as an adult) I am bewildered as to how that 30 feet of digestive machinery is still functioning. And yet it does.

Reasonably well, at least. There is that whole ice cream thing, but let’s not dwell on that (Click here to learn more about that).

Something’s missing in my life. Source: Morellisices

Despite all the accolades for its robustness, our guts do represent one of the greatest opportunities for foreign organisms to invade our bodies. It is a very supportive, resource-rich environment for many microbes, and they can easily take up residence without us even knowing.

Source: Huffington Post

And this is an important aspect of our guts, as it is becoming increasingly clear that some of these uninvited guests can have a very negative impact on our bodies.

Recently, there are been a huge amount of attention in Parkinson’s research focused on the gut and the bacteria that live within it for this very reason.

But what is the connection between the gut and Parkinson’s?

Continue reading “Does Parkinson’s have us by the short and curli?”

Ptbp1: “One and done”(?)

# # # #

Recently a lot of media attention has been focused on a new study that reported the replacement of lost dopamine neurons in a mouse model of Parkinson’s, which resulted in the correction the associated behavioural/motor issues.

The researchers involved achieved this amazing feat by simply reducing a single protein in a special type of helper cell in the brain, called astrocytes. By lowering the levels of the protein, they were able to transform the astrocytes into dopamine neurons.

Intriguingly, the study represented independent replication of a previous study that demonstrated a similar result – transformation of astrocytes inside a mouse brain into dopamine neurons by reducing a single protein.

The protein in both studies is called Ptbp1, and in today’s post we will discuss what this protein does, what the new study found, and what the implications of this work could be.

# # # #


Source: Howtogeek

Earlier this year, I stated in my 2020 wish list for Parkinson’s research (Click here to read that post) that one of the big themes I was hoping to see more of was further research on regenerative approaches for the condition.

We have discussed this a few times, but any “curative” treatment for Parkinson’s will require 3 components:

  1. A disease halting mechanism – to slow/stop the progression of the disease
  2. A neuroprotective agent – to protect the remaining cells & provide a nurturing environment for,
  3. Some form of restorative/regenerative therapy – replacing what has been lost

Now the encouraging news is that if you look at the SoPD “The Road Ahead: 2020” post, you will see that there is a great deal of research being conducted on all three of these components at the clinical stage (in addition to vast amounts of work on the preclinical level).

But it is fair to say that the bulk of the clinical research being conducted on restorative therapy for Parkinson’s is centred around the transplantation of stem cell-derived dopamine neurons to replace the cells that have been lost in Parkinson’s (click here to read a recent SoPD post on this topic).

Embryonic stem cells in a petridish. Source: Wikipedia

In my wish list for 2020, I was hoping to see regenerative approaches beyond the well trodden path of cell transplantation (growing cells in culture and then injecting them into the brain).

Dopamine neurons (green) in cell culture. Source: Axolbio

Rather, I was hoping to see more research on new regenerative approaches that target/manipulate endogenous pathways in the brain – forcing changes within the central nervous system itself.

I didn’t have high expectations in this department, but I have to admit that now I have been pleasantly surprised by the number of research reports that have been published thus far this year highlighting novel regenerative approaches. We have discussed several of them here on the SoPD already (Click here and here for examples), and today we are going to review another which was recently published in the prestigious scientific journal Nature.

This is what all the news papers have been talking about?

Indeed. There has been a lot of media attention focused on this research report.

So what does the new study report?

Continue reading “Ptbp1: “One and done”(?)”

Monthy research review – June 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 June 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
  • Review articles/videos

# # # #


So, what happened during June 2020?

In world news:

June 2nd – Researchers reported that animal DNA extracted from parchments helped them piece together the Dead sea scrolls – a fascinating story (Click here to read the resesarch report and Click here to read a summary of the research).

June 6th – US Black Lives Matter protests entered their 12th consecutive day, and countries around the world held their own protests.

June 16th – Researchers report that there may be as many as six billion Earth-like planets in our galaxy (Click here to read more about this).

20th June – The Siberian town of Verkhoyansk broke the record for the highest temperature ever recorded within the Arctic Circle – it hit 38 degrees Celsius (that is 100.4F). The average daily high for the town in June is 19.9 degrees Celsius. Surrounding cities recorded similar temperatures (Click here to read more about this).

June 29th – Scientist reported that an asteroid impact (and not volcanoes) made the Earth uninhabitable for dinosaurs

 

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

In June 2020, there were 743 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5,308 for all of 2018 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 “Monthy research review – June 2020”

The hunt for a vaccine

# # # #

This week, the biotech firm AFFiRiS published the long awaited results of their Phase 1 clinical trial evaluating a vaccine for Parkinson’s. The vaccine – called PD01A – targets a protein that clumps/aggregates together in certain neurons in the brains of people with Parkinson’s.

The multi-year study suggests that the treatment is safe and tolerated. In addition, it causes the immune system to generate antibodies that target the aggregated form of alpha synuclein.

And while it must be remembered that this is a small, open-label study, there are some intriguing statements made in the report.

In today’s post, we will discuss what PD01A is, review the results of the clinical study, and explore what happens next.

# # # #


Source: NHI

As the world awaits the development of a vaccine that will combat COVID-19, the neurodegenerative research community has quietly been watching a biotech company in Austria that has been developing a vaccine of a different sort: A vaccine for Parkinson’s.

The company is called AFFiRiS:

Source: Twitter

And this week they published the results of their Phase 1 safety/tolerability clinical trial of their immunotherapy treatment (PD01A) that they are testing in people with recently diagnosed Parkinson’s.

What is immunotherapy?

Continue reading “The hunt for a vaccine”

Dexamethasone for Parkinsons? Not so elementary my dear Watson

# # # #

Artificial intelligence (AI) is being applied by scientists to all aspects of Parkinson’s research. From drug discovery to protein folding, the power of these supercomputers is being utilized and it is starting to bear interesting pieces of fruit.

Recently a group of scientists in Toronto (Canada) have reported a study using AI to identify clinically available drugs that may reduce the risk of developing Parkinson’s (or slow it onset).

Specifically, using IBM’s Watson super computer, they screened through a medical records database (the Ontario Drug Benefit), and identified several classes of drugs that reduced the risk of developing PD.

In today’s post, we will review the results of the recent report and consider the implications.

# # # #


Dexamethasone. Source: Sky

This week we received fantastic news from the coordinators of the UK RECOVERY Trial that they have identified an agent that appears to have a significant impact on improving survival for individuals affected by COVID19 infections.

The RECOVERY (Randomised Evaluation of COVid-19 thERapY) trial – launched across 175 NHS hospitals in the UK in March – is one of the world’s largest randomized, controlled trials for coronavirus treatments (Click here to read more about this details of the trial). The study currently has more than 11,000 patients enrolled and it is evaluating 6 agents for their ability to combat the COVID-19 virus, SARS-CoV-2.

This week the researchers conducting the study announced that the corticosteroid dexamethasone – a medicine that reduces inflammation by mimicking anti-inflammatory hormones produced by the body – was able to reduced the risk of dying in infected individuals (on receiving oxygen therapy but were not on ventilators) by 20%. The agent had no effect on people with less severe cases of COVID-19.

Source: Bloomberg

It is a remarkable achievement – involving 2,100 patients who received the drug at a low-to-moderate dose of 6 milligrams per day for 10 days and were compared against approximately 4,000 patients who received standard care for the coronavirus infection (UPDATE 22/6/2020: a manuscript of the result is now avaiable – click here to read it).

Yeah, it’s brilliant. But what does this have to do with Parkinson’s?

Well, very recently dexamethasone has been identified as potentially having an effect on another medical condition.

Care to take a wild guess as to which condition that might be?

Continue reading “Dexamethasone for Parkinsons? Not so elementary my dear Watson”

Oligodendrocytes?!?

# # # #

Oligodendrocytes are a supportive cell in the brain. They produces a protective coating – called myelin – which insulates the primary projecting branch of neuronal (called axons) and aids in the rapid transmission of signals in the brain.

Medical conditions associated with these cells include the inflammatory condition of multiple sclerosis. It is fair to say that oligodendrocytes have been largely neglected in the context of Parkinson’s research.

But that might be about to rapidly change.

In today’s post, we will discuss what oligodendrocytes do, and explore new research that may point towards a role for oligodendrocytes in Parkinson’s.

# # # #


Source: Youtube

The name “oligodendrocyte” comes from the Greek.

‘Oligos’ (ολιγος) meaning small or little; ‘dendros’ (δενδρος) meaning tree or bush; and ‘kytos(κύτος) meaning ‘cavity’ or ‘cell’.

The name was given to cells in the brain with small branches by the Spanish neuroscientist Dr Pío del Río Hortega (1882–1945):

Pío del Río Hortega. Source: RTVE

Del Río Hortega developed a staining method that allowed him to differentiate what the great Ramón y Cajal referred to as the “third element” of cells in the brain. Initially calling them “interfascicular cells”, Del Río Hortega later changed the name to oligodendroglia.

Title: La glía de escasas radiaciones (oligodendroglía).
Author: Del Río-Hortega P.
Journal: Bol. Real Soc. Esp. Hist. Nat.(1921). 21, 63–92.
PMID: N/A

(For those who would like to read more about Pio del Río-Hortega – click here for an excellent review)

Cool. But what do oligodendrocytes do?

Continue reading “Oligodendrocytes?!?”

Disney’s “Attack of the synucleozid from Jupiter”

 

Alpha synuclein is widely viewed as one of the bad guys in Parkinson’s. The clustering and aggregation of this protein is one of the main pathological hallmarks of the condition.

Researchers led by scientists at the Scripps Research institute in Florida have developed a new drug-like compound that selectively prevents the production of alpha synuclein protein.

They have called their new compound “synucleozid“.

In today’s post, we will look at what alpha synuclein is, what synucleozid does, and how this approach could potentially help in treating Parkinson’s.

 


 

 

In a recent SoPD post, we discussed research focused on levodopa-induced dyskinesias which was led by scientists from the Scripps Research Institute (Click here to read that post). The Scripps is the largest private, not-for-profit medical research facility in the United States and among the largest in the world.

It is headquartered in La Jolla, California, but interesting fact: It has a sister facility in Jupiter, Florida.

Scripps Research in Jupiter. Source: Weitz

Officially opened on February 26th 2009, the establishment of the Scripps Florida campus was made possible by a one-time US$310 million federal economic development fund. The institute now survives on research grants, gifts, and contracts. In the future, some of the funding may also come from royalties generated by intelluctual property based on medical discoveries made at the facilities.

And some of those medical discoveries may involve novel ways to treat Parkinson’s.

Really? Such as?

Recently a research team led by Professor Matthew Disney published a report that takes an interesting approach towards trying to tackle Parkinson’s.

Professor Matthew Disney. Source: Scripps

What does it involve?

It involves reducing levels of the Parkinson’s associated protein alpha synuclein.

What is alpha synuclein?

Continue reading “Disney’s “Attack of the synucleozid from Jupiter””

Monthly Research Review – May 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 May 2020.

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

  • Basic biology
  • Disease mechanism
  • Clinical research
  • New clinical trials (Oooh, new section for 2019!)
  • Clinical trial news
  • Other news
  • Review articles/videos

 


So, what happened during May 2020?

In world news:

May 11th – In two studies published in Nature, and Nature Ecology and Evolution, scientists describe hominin remains and artefacts excavated from the Bacho Kiro Cave (in Bulgaria) that indicate early humans were present in Europe around 46,000 years ago – suggesting the species shared the continent with Neanderthals for longer than previously thought.

May 18th – A Maryland restaurant preparing to reopen amid the ongoing COVID-19 pandemic unveiled its fleet of wheeled bumper tables designed to enforce social distancing:

 

May 27th – South Korean schools reopened as the country began easing COVID-19-associated lockdown restrictions.

May 29th – South Korea re-closed 200 schools as new cases of COVID-19 spike to 79, the highest daily figure in two months.

May 30th – The age of commercial human spaceflight officially began

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

In May 2020, there were 782 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4565 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 6 pieces of Parkinson’s news

Continue reading “Monthly Research Review – May 2020”

Oleh Hornykiewicz (1926-2020)

# # # #

This week it was announced that Oleh Hornykiewicz had passed away.

I appreciate that most readers will not know who he is, but understand that his contribution to Parkinson’s research was important.

Not only was he instrumental in the discovery that dopamine is significantly reduced in the Parkinsonian brain, but he also demonstrated that levodopa treatment can help restore function.

In today’s post, we remember Oleh Hornykiewicz.

# # # #


It was sad to hear of the passing away of Oleh Hornykiewicz this week.

Most readers will have little clue as to who he was, but he played a very important role in the development of the Parkinson’s treatment we know of as levodopa therapy.

Very early in the 20th century, a chemical called dopamine was discovered, but no one really knew anything about it until a young Swedish research named Arvid Carlsson started to play with it.

Win 1113

Prof Arvid Carlsson. Source: Alchetron

In 1957, Carlsson discovered that when he injected a drug called reserpine into the brains of rabbits, the animals exhibited limited ability to move. He found that reserpine depleted levels of dopamine in the brains of the rabbits. He also discovered that by injecting the dopamine precursor – levodopa (more on this below) – into those same animals, he was able to rescue their motor ability. Importantly, he found that the precursor (called 5-hydroxytryptophan) to another chemical called serotonin, it was not capable of reversing the reduction in motor ability, indicating that the effect was specific to levodopa and dopamine.

He published this amazing result in the prestigeous scientific journal ‘Nature’:

avid

Title: 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists.
Authors: Carlsson A, Lindqvist M, Magnusson T.
Journal: Nature. 1957 Nov 30;180(4596):1200. No abstract available.
PMID: 13483658       (the article on the Nature website – access required)

This was a fantastic discovery.

But what to do with it?

And that is where an Austrian researcher named Oleh Hornykiewicz becomes part of the story.

Continue reading “Oleh Hornykiewicz (1926-2020)”

PDCORE

# # # #

Assessing the progression of Parkinson’s is a very difficult task, but accurately doing so is critical to our ability to evaluate the disease modifying potential of new therapies.

The clinical measures currently used in clinical trials have been developed using large longitudinal studies that assessed individuals over long periods of time. But the utility of these tools have been called into question as we try to measure subtle changes in progression.

Using post-hoc (after the fact) analysis of recent clinical trial data, however, researchers have recently proposed a new method of assessment that they call “The Parkinson’s Disease Comprehensive Response” (or PDCORE).

In today’s post, we will discuss what PDCORE is and how it was identified.

# # # #


Joe Brown. Source: theBMC

I am not a climber (in fact, despite being rather tall, I am not very good at heights).

I certainly do not understand the mentality of people that need to climb mountains just to reach the top, particularly if they are simply following the same route as every other person climbing the same peak. And images of traffic jams in the “death zone” (above 8,000 meters) of Everest completely befuddle me.

Waiting for bragging rights?!? Source: NYTimes

So on the 15th April of this year when I heard about the passing of a climber named Joe Brown, I thought nothing of it… until that is, I read his story.

And more importantly his philosophy.

You see, Joe was deeply passionate about climbing and was considered one of the best by many. But for Joe it was never about getting to the top of the mountain, it was always about finding a new route up a mountain or a new way of doing something that compelled him.

Joe Brown. Source: Economist

This is a mentality I can appreciate.

It is also an idea that the Parkinson’s research community needs to embrace. If we are simply doing things because they are the way we have always done things, something is wrong.

Like Joe Brown, we need to be exploring new routes.

Which is why in today’s post we will be discussing PDCORE.

What is PDCORE?

Continue reading “PDCORE”