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

~ Simon ~ 4 Comments

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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.

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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?” →

The Stanford Parkinson’s Disease Plasma Study

~ Simon ~ 3 Comments

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Researchers in California have been conducting a different kind of Parkinson’s clinical trial. Rather than testing a drug or a special diet/exercise regime, they have been giving participants in their study a regular infusion of plasma.

If you remove all of the cells from blood, the yellowish liquid that remains is called plasma. In medicine, plasma is usually used to boost a patient’s blood volume to help reduce shock. But recently researchers have been experimenting with giving older individuals infusions of plasma collected from young individuals to see if this has any beneficial effects.

A group of researchers at Stanford University have been leading a study examining the safety of infusions of plasma (collected from young people) in a cohort of individuals with Parkinson’s. This week they published the results of their study.

In today’s post, we will discuss what plasma is made of, why young plasma may help in neurodegenerative conditions, and review the results of the new study.

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Source: KhanAcademy

There are three chief components of blood:

  • Red blood cells
  • White blood cells
  • Plasma

Red blood cells carry oxygen to distant parts of the body and they also remove carbon dioxide. And by volume, the red blood cells constitute about 45% of whole blood. White blood cells are the immune cells, fighting off infections etc. And they – this may surprise you – make up only 0.7% of whole blood.

That might sound like a tiny fraction, but understand that within a single drop of blood (50 ul) there are approximately 5 million red blood cells, and 5,000 to 25,000 white blood cells.

Apologies to the squeamish. Source: Science

And in total the human body contains about 4.5 litres (or 1.2 gallons) of blood. That’s a whole lot of drops. Plenty of white blood cells to help keep us healthy.

And what about plasma?

Plasma is the stuff that all of the red and white blood cells sit in. It has a yellowish tinge to it, and it makes up the other 54.3% of whole blood.

It contains 92% water and 8% ‘other stuff’.

Apologies for the very technical term (‘other stuff’), but there is a great deal of interesting stuff in that ‘other stuff’.

What do you mean ‘interesting’?

Continue reading “The Stanford Parkinson’s Disease Plasma Study” →

Ptbp1: “One and done”(?)

~ Simon ~ 5 Comments

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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.

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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

~ 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 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

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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 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 “Monthy research review – June 2020” →

GBA: Wider regulation = wider implications

~ Simon ~ 9 Comments

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Tiny variations our DNA can have a significant impact on our lives.

For the last 20 years, Parkinson’s researchers have been collecting data highlighting ‘genetic risk factors’ that are associated with increasing one’s risk of developing the condition.

More recently, however, these same scientists have started shifting their attention to the factors that modulate these genetic risk factors – and some of those influences are also genetic.

In today’s post, we will look at new research exploring genetic variations that influence the effect of the Parkinson’s-associated GBA genetic variants, and discuss why this research has huge implications not only on how we conduct clinical trials, but also on how we will treat Parkinson’s in the future.

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Prof Craig Venter. Source: ScienceMag

In June 2000, when the results of the first human genome sequencing were announced during a ceremony at the White House, the DNA sequencing pioneer Prof Craig Venter observed that “The concept of race has no genetic or scientific basis“.

He was suggesting that due to genetic variations among human individuals and populations, the term ‘race’ cannot be biologically defined. There was simply no evidence that the broad groups we commonly refer to as “races” have any distinct or unifying genetic identities (Click here for interesting additional reading on this).

Source: Phillymag

Prof Venter’s words were a powerful statement regarding the incredible variability within our genetic make up.

And that variability is even more remarkable considering that we are all 99.9 percent genetically identical.

So how do we explain the variability then?

Continue reading “GBA: Wider regulation = wider implications” →

The hunt for a vaccine

~ Simon ~ 4 Comments

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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.

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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

~ Simon ~ Leave a comment

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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.

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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” →

GTCA

~ Simon ~ 6 Comments

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Today’s post is ‘blue sky’ stuff (meaning that it is not going to be in the clinical any time soon), but it is utterly fascinating (almost sci fi) research.

Scientists at Stanford University have developed a method by which they can reprogram cells to use synthetic materials (provided by the scientists themselves) to build functional artificial structures.

And to add to the sci fi nature of it, they have called this approach “GTCA” (“genetically targeted chemical assembly”).

In today’s post, we discuss what GTCA is, what they found in their study, and where this wondrous discovery could go next.

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Prof Karl Deisseroth. Source: Ozy

This is Karl Deisseroth.

Looks like the mad scientist type, right? Well, remember his name because this guy is fast heading for a Nobel prize.

Possibly two.

He is the D. H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University. And he is one of the leading researchers in a field that he basically started. That field is called optogenetics (Click here to read a previous SoPD post about this topic).

Optogenetics. Source: Harvard

He also developed (along with Kwanghun Chung) a better way of visualising the brain called CLARITY.

CLARITY is a technique that transforms intact tissue (like the brain) to make it completely transparent. With a clear brain – and some additional biological techniques – an exceptionally detailed map of neuronal pathways can be generated.

For an example, watch this video:

Prof Deisseroth and colleagues are also seeking to pioneer additional areas of neuroscience, and in today’s post we will be exploring a new research report that could have important implications for Parkinson’s.

How so?

Here on the SoPD we often discuss research focused on the slowing or stopping of Parkinson’s, but often overlooked are efforts to restore and rejuvenate. Replace the lost cells and circuits that have been lost to degeneration.

At the start of this year (in the 2020 wish list post), I said that I was hoping to see “a focus on rejuvenation”.

And it is fair to say that Prof Deisseroth and colleagues appear to be trying to deliver on that particular wish.

Interesting. What have Prof Deisseroth and his team done?

Continue reading “GTCA” →

Oligodendrocytes?!?

~ Simon ~ 3 Comments

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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.

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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”

~ Simon ~ 1 Comment

 

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”” →