A tête-à-tête about TET2

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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”

Monthy research review – August 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 August 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 August 2020?

In world news:

August 4th – Two explosions caused by unsafely stored ammonium nitrate killed over 220 people, injure thousands, and severely damage the port in Beirut, Lebanon.

August 16th – In Death Valley (California), the appropriately named Furnace Creek (population of 24) logged a day time high temperature of 130° Fahrenheit (54.4° Celsius).

Augst 20th – The US FDA holds on Emergency Use Authorization for convalescent plasma the treatment of COVID–19, with health regulators stating the “importance of robust data through randomized control trials” and “that a pandemic does not change that”. Apparently the emerging data on the treatment was “too weak”

August 23rd – The US FDA issued “Emergency Use Authorization for convalescent plasma as potential promising COVID–19 treatment, Another Achievement in Administration’s Fight Against Pandemic” (Source). What a difference 3 days and no data makes….

August 24th – A 33 year old man in Hong Kong became the first confirmed case of coronavirus reinfection (additional cases have been confirmed). Humans appear to have a short immunity to COVID-19 (2-3 months, similar to influenza).

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

In August 2020, there were 890 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6,948 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 “Monthy research review – August 2020”

Can sigma-1 get it done?

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An Australian charity seeking to find disease modifying therapies for Parkinson’s – The Shake It Up Australia Foundation – has announced a commitment to partially fund a clinical trial with a biotech firm called Anavex Life Sciences.

The trial will focus on a drug called ANAVEX2-73 (also known as ‘blarcamesine’). This experimental treatment is a Sigma-1 receptor agonist

In today’s post, we will discuss what the Sigma-1 receptor does, we will review some of the Parkinson’s research that has been conducted on this protein, and we will discuss what we know about the potential trial.

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A man on a mission. Source: Goulburnpost

The gentleman in the photo above is named Clyde Campbell.

True blue Aussie, innovative robotics engineer, keen sportsman, and all round nice guy.

Clyde also has Parkinson’s, which was diagnosed in 2009 after he noticed a tremor in his left hand while holding notes at a business meeting. After dealing with the initial shock of this life changing event, he turned his attention to doing something about it.

Clyde simply could not sit still and not do anything about his situation, so he grabbed the bull by the horns and decided to shake things up.In 2011, Clyde (and his brother Greg) founded a charity called the Shake It Up Australia Foundation:

Since its founding, the foundation has supported 38 Parkinson’s research projects across 12 institutes, with over AUS$11.5 million in funding. In addition, the organisation is a key partner in the Australian Parkinson’s Mission (Click here to read a previous SoPD post on this project).

To learn more about Clyde, watch this video where he shares his story:

This week the Shake It Up Australia Foundation made a big announcement.

What did they say?

Continue reading “Can sigma-1 get it done?”

The ibuprofen post

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Ibuprofen is a nonsteroidal anti-inflammatory drug that is used for treating pain, fever, and inflammation.

Previous preclinical research has demonstrated that ibruproen has the ability to reduce the loss of neurons in models of Parkinson’s, and epidemiological data suggests that it may lower the risk of actually developing the condition.

Recently published research points towards a specific sub-set of individuals vulnerable to Parkinson’s that ibuprofen may be particularly useful for: LRRK2-genetic variant carriers.

In today’s post, we will discuss the origins of ibruprofen, review some of the previous research indicating neuroprotective properties, and do a deep dive into the new LRRK2 data.

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Source: BBC

This story starts in 1953.

And it begins with two chemists – Stewart Adams and John Nicholson (Stewart is the chap in the banner photo at the top of this post holding the container of pills) – who were both working for Boots, a health/beauty retailer and pharmacy chain in the UK.

Source: Boots

Stewart and John were on a mission: To produce a new drug for rheumatoid arthritis.

You see, in 1953 there were only two drugs available for treating inflammatory pain: a corticosteroid drug and high dose aspirin. And neither of them was ideal. The chemists started their quest by looking for the activity of variations of aspirin, hoping to find a powerful alternative.

Adams (left) & Nicholson (middle). Source: Boots

Their search was not easy – it took 16 years and they screened over 20,000 molecules – but output of that effort was a drug called ibuprofen (sold under ‘Brufen’).

Legend has it that Adams initially tested the drug on himself as treatment for a particularly bad hangover (Source).

Ibuprofen was launched on the 3rd February 1969 as a treatment for rheumatoid arthritis in the United Kingdom, and it was introduced in the United States in 1974. It went on to become one of the most prescribed drugs in history and it is still widely used. In fact in 2015, Boots UK sold an average of one pack of ibuprofen every 2.92 seconds and, across all UK retailers, the sales figures for the medicine reached over £150 million.

This is all very interesting, but what does it have to do with Parkinson’s?

Continue reading “The ibuprofen post”

Billion dollar bets: Denali+Biogen

 

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This week the biotech firm Denali Therapeutics made two major announcements regarding the development of their LRRK2 inhibitor program for Parkinson’s.

First, the company revealed that they have signed an agreement with the pharmaceutical company Biogen to co-develop and co-commercialise small molecule inhibitors of LRRK2 for Parkinson’s.

Second, Denali also announced that they have a green light from the US FDA to start the next phase of clinical testing of their LRRK2 inhibitor DNL151.

In today’s post, we will discuss what is meant by LRRK2 inhibitor, what the details of the announcements are, and what all of this means for the Parkinson’s community.

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Denali. Source: Wikipedia

Peaking at 20,310 feet (or 6,190 m) above sea level, Denali (Koyukon for “the high one”; also known as Mount McKinley) is the highest mountain in North America. The first verified ascent of this Alaskan mountain occurred on June 7, 1913, when four climbers (Hudson Stuck, Harry Karstens, Walter Harper, and Robert Tatum) conquered it.

Tatum (left), Karstens (middle), and Harper (right). Source: Gutenberg

Robert Tatum later commented, “The view from the top of Mount McKinley is like looking out the windows of Heaven!

More recently another adventurous group associated with ‘Denali’ have been trying to scale lofty heights, but of a completely different sort to the mountaineering kind.

Founded in 2013 by a group of former Genentech executives, San Francisco-based Denali Therapeutics is a biotech company which is focused on developing novel therapies for people suffering from neurodegenerative diseases. Although they have product development programs for other condition (such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease), Parkinson’s is definitely their primary indication of interest.

And this week, the company made two major announcements with regards to their Parkinson’s research program.

The first announcement was that Denali have signed an agreement with the pharmaceutical company Biogen to co-develop and co-commercialise small molecule inhibitors of LRRK2 for Parkinson’s (Click here to read the press release).

What is LRRK2?

Continue reading “Billion dollar bets: Denali+Biogen”

Monthy research review – July 2020

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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 July 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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What happened in July 2020?

In world news:

July 1st – With the introduction of the new national security law, academics in Hong Kong expressed concern about being able to recruit talented researchers and to import critical high tech equipment (due to international sanctions – click here to read more about this).

July 16th – Six year old Bridger Walker gained social media fame after saving his sister from being attacked by a charging dog. Bridger was bitten several times on the head and face, requiring 90 stitches. Celebrities praised his brave actions:

 

July 17th – Capt Sir Tom Moore was knighted – what a legend! (Click here to read more about this).

July 25th – A record high temperature of 21.7°C (71.1°F) is recorded on the Arctic archipelago of Svalbard, according to the Norwegian Meteorological Institute.

July 31st – Researchers reported that human sperm do not swim the way we thought they did (rather rolling and lopsided tail flicks keep the cells moving in a straight line – 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 July 2020, there were 753 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6058 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 – July 2020”

Smarter than the average björn

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Certain life-style and environmental factors may render individuals more vulnerable to Parkinson’s, and a better understanding of them could aid in effects to reduce the incidence of the condition.

Some of these risk factors (such as smoking and drinking coffee – PLEASE DO NOT START SMOKING!) can reduce the risk of developing Parkinson’s, while others such as exposure to pesticides can increase the chances of PD.

Recently, researcher in Sweden have made a rather curious association: High IQ is associated with Parkinson’s

In today’s post, we will discuss the results of this new study and we will speculate a little with regards to what they could mean for Parkinson’s.

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Lund. Source: Copenhagen-travel

When I was younger and less beautiful, I spent half a decade of my life enjoying the charms of a small Swedish city called Lund.

I was there to do a PhD (the chance of a life time for a simple country boy from the back-waters of third world New Zealand), but I absolutely fell in love with the place (a quiet, cobble-stoned, academic town) and the local customs.

Source: Beaps

Life in Sweden was really good. They had a fantastic quality of life, but more importantly they encouraged a very strong sense of social consciousness, inclusion, and justice.

But there was one aspect of ‘svenska livet’ that surprised me.

Despite a strong military history, Sweden chose to adopt a policy of neutrality in 1815 and it has not taken part in any armed warfare since that time (with the exception of peacekeeping). And yet, the country has maintained mandatory military service (in Swedish: värnplikt) for men since 1901 (the practice was paused between 2010 and 2017, but has subsequently been restarted on a reduced level).

Interesting, but what does mandatory military service have to do with Parkinson’s?

Continue reading “Smarter than the average björn”

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

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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

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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”(?)

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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”(?)”