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Monthly Research Review – October 2021

~ Simon ~ 6 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 October 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during October 2021?

In world news:

October 3rd – The International Consortium of Investigative Journalists and assorted media partners publish a set of 11.9 million documents leaked from 14 financial services companies known as the Pandora Papers, revealing offshore financial activities that involve multiple current and former world “leaders”… and nothing happened.

 

October 15th – TV scriptwriters Agustín Martínez, Jorge Díaz and Antonio Mercero shocked guests at the Planeta prize ceremony, when they took to the stage to collect the main €1m prize and reveal that the celebrated crime author, Carmen Mola, does not actually exist.

 

October 16th – The Lucy spacecraft is launched by NASA, the first mission to explore the Trojan asteroids (Click here to learn more about this).

 

October 22nd – The UK Health Security Agency announced the offshoot of COVID19-Delta, known as AY.4.2 (has two mutations in the spike protein) was designated a “variant under investigation”. Preliminary evidence suggests that this subvariant could be 10-15 per cent more transmissible than the original Delta (Click here to read more about this).

(Let’s play a game of “Find the mask”. And yes, I’m picking on West Ham fans)

October 31st – The month started badly for World “leaders”, and it finished much the same way. They began flying into Glasgow for COP26 to talk and… do nothing about rising levels of atmospheric green house gases (What a waste of public morale. Joe really missed a big opportunity, and Boris… was simply Boris)

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

In October 2021, there were 868 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (10,046 for all of 2021 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 2021” →

Mo better for TEVA with Modag?

~ Simon ~ 4 Comments

 

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This week the pharmaceutical company TEVA Pharmaceuticals Industries Ltd has announced a deal with a small German biotech firm called MODAG.

The two companies are forming a strategic collaboration on the exclusive worldwide licensing and development of MODAG’s lead compound anle138b.

Anle138b is a small molecule inhibitor of the believed to be toxic forms of the Parkinson’s-associated protein alpha synuclein.

In today’s post, we will discuss what is known about anle138b and the implications of this new partnership.

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Source: SLE

In 1901, Haim Salomon and his brother-in-law Moshe Levin established a small wholesale drug business, near the Nablus Gate in Jerusalem. They called it “Salomon and Levin”. A few years later, Yitzhak Elstein, another of Haim Salomon’s brothers-in-law, joined the firm and they changed the name of the company to SLE – Salomon Levin and Elstein.

Source: SLE

From these humble beginning, grew a pharmaceutical juggernaut that we know today as TEVA Pharmaceuticals.

TEVA – meaning “Nature” in Hebrew – is now an international producer of pharmaceutical agents, with 40,000 employees working across 65 manufacturing facilities in more than 30 countries. The company has a portfolio of more than 3,500 medicines, and they produce approximately 85 billion tablets and capsules per year (Source).

Does TEVA produce any drugs for Parkinson’s?

Yes, Azilect (rasagiline) – an approved monoamine-oxidase B inhibitor for the treatment of Parkinson’s – was developed by Teva Pharmaceuticals.

In addition, they are actively developing novel therapies. And this week they signed a really interesting deal to collaborate with a small German biotech company called MODAG.

What does MODAG do?

Continue reading “Mo better for TEVA with Modag?” →

ELOVL me tender

~ Simon ~ 2 Comments

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Astrocytes are a non-neuronal cell type in the brain that play an important supportive role – nurturing neurons and helping to maintain homeostasis in the central nervous system.

When neurons get damaged or stressed, however, astrocytes can do a Jekyll & Hyde-like transformation and start releasing a toxic substance that helps to kill neurons. This nasty change in the temperament of astrocytes is believed to play a role in neurodegenerative conditions.

Exactly what the released toxic substance is has long been a mystery.

Until now it seems.

But the nature of the presumed substance is something of a surprise to the research community.

In today’s post, we will review a new research report that points towards saturated lipids as the mediators of astrocyte-induced toxicity and we will consider what this could mean for future therapies for neurodegenerative conditions.

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One of my favourite scientists to listen to is Ben Barres.

It is wonderful to go back and watch some of his old videos. Not just because you learn so much from him, but also for the passion that he always had when discussing general science, his research, and other things he believed in.

For example, watch the first 10-15 minutes of this video:

The presentation above was made on January 9th 2017, and despite knowing that he had less than a year to live, you can hear the energy and excitement in his voice for the  material he is presenting. He desperately wanted to share the information and to learn what others might think about it.

He was truly an amazing individual.

Even more so, because almost 4 years after he died, Ben is still publishing spectacular research.

Wait. What?

Continue reading “ELOVL me tender” →

Repurposing bumetanide for Alzheimer’s

~ Simon ~ 5 Comments

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Bumetanide (Bumex) is a diuretic drug (a medication that removes water, by increasing the production of urine). It is used to treat swelling caused by heart failure or liver or kidney disease. It is a widely used drug that has been well characterised in clinical use.

Recently researchers conducted a screening study to identify clinically available agents that might be useful in the treatment of the cognitive decline associated with a genetic risk factor for Alzheimer’s: APOE4 

The top drug identified in their study was bumetanide.

In today’s post we will discuss what APOE4 is, we will review the results of the new study, and we will look at why these findings could be interesting for Parkinson’s.

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Source: Pharmacysafety

Many years ago, I was at a patient-research interaction event and a world-leading genetics researcher was asked by someone in the audience if they had had their DNA sequenced.

They said ‘no‘.

The person asking the question frowned and asked ‘why not? You have all the technology and knowledge – don’t you want to know more about yourself?‘

The researcher replied “No. Having your DNA sequenced should not be taken lightly. You might learn stuff about yourself that you don’t want to know”

They used the example of possibly being an APOE4 carrier (who have a higher risk of cognitive decline during aging). The geneticist declared that they would rather not know that kind of information for fear of the impact that it could have on their life.

The questioner respected the honest answer and the conversation that followed was really interesting. More recently, however, as we have learned more about APOE4 and new drugs are being targeted at this risk factor, I have often wondered if their decision would still stand. Are we approaching an age when we might want to know if we are APOE4 carriers?

Hang on a moment. What is this APOE4 thing?

Continue reading “Repurposing bumetanide for Alzheimer’s” →

Mind blowing modulation of mind

~ Simon ~ 2 Comments

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Neuromodulation of specific circuits in the brain represents a means of adjusting deficits in neural performance and significantly improving quality of life.

Deep brain stimulation has been widely applied to the treatment of Parkinson’s since Alim Benabid first discovered that electrical stimulation of the basal ganglia improves the symptoms of the condition in the late 1980s.

Now researchers are attempting to refine the approach further with new technology (such as optogenetics) and more specific targeting – stimulating only particular types of neurons – with impressive results and potentially immediate implications for treatment.

In today’s post, we will discuss what optogenetics is, review some new preclinical results, and explore those potentially immediate implications for the treatment of Parkinson’s.

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Vienna. Source: Worldofcruising

In 2016, I was lucky enough to be at the “Dopamine” research conference in Vienna (Austria).

It is a wonderful city, the late summer weather was perfect, and an amazing collection of brilliant researchers had gathered to focus on all things dopamine-related for four days. The conference highlighted all the exciting new research being done on this chemical.

Source: Medium

There was – of course – a lots of research being presented on Parkinson’s disease as well, given that dopamine plays such a fundamental role in the condition.

And I was sitting in the lecture presentations, listening to all these new results being discussed, thinking how fantastic it all was, when a researcher from Carnegie Mellon University stood up and (without exaggeration) completely – blew – my – mind!

Basically sums my reaction. Source: Canacopegdl

Seriously. I was left speechless by the results presented.

Wow, what were the results???

Continue reading “Mind blowing modulation of mind” →

Omega+omega=a mega result?

~ Simon ~ 13 Comments

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Today’s post involves a product from a company. The SoPD has not had any contact with the company or associated parties. This post should not be considered as an endorsement or an advertisement of the product. Recently published results from a clinical trial were interesting enough to stimulate this discussion.

Omega-3 and omega-6 represent two families of fatty acids that have important biological functions in our bodies. A careful balance of them is required in our diets in order for us to function normally.

A recent report from a small clinical trial indicates that daily supplementation with a formulation that includes these molecules could have beneficial effects in Parkinson’s motor symptoms.

In today’s post, we will discuss what omega-3 and omega-6 fatty acids are, we will review the new report outlining the study results, and discuss why these results could be interesting.

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Source: Foodandwine

Back when I was young and less beautiful, I had a formidable appetite.

Seriously. My consumption rate was the stuff of legend. There were local all-you-can-eat restaurants that would refuse to serve me, for fear that I would liquidate them.

But I am man enough to admit that I was nothing compared to my friend Jason’s younger brother “Peter”.

One day the three of us went down to the local MacDonald’s during one of their promotions (something like 50 cents per Big Mac) and we challenged ourselves to see who could eat the most. Jason sensibly stopped after finishing 3 burgers, while I had to finally throw in the towel on my 6th burger (to be honest I was struggling from burger #4).

Source: Thrillist

Jason and I had to ask Peter to stop on burger #9.

I kid you not.

Think about that for a second: NINE Big Macs!

We were watching in bloated horror as this skinny teenage kid was just sitting there – with a milk shake in one hand – throwing back these burgers like they were nothing. Even now it is grotesque to reminisce about, and I really wonder if we didn’t do serious damage to our livers that day.

That is disgusting. What does it have to do with Parkinson’s?

Well, we all do silly things when we are young and invincible. At that age it seems like you can eat whatever you want and there are no consequences. But of course as we get older, we need to start carefully considering what you are putting into your body.

And recently the results of a clinical study were published that indicate that what we consume could also influence the course of Parkinson’s.

What do you mean?

Continue reading “Omega+omega=a mega result?” →

Making a (G)case for quetiapine

~ Simon ~ 8 Comments

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Drug repurposing (repositioning, reprofiling or re-tasking) is a strategy of identifying novel uses for clinically approved (or experimental) drugs that fall outside the scope of the original medical indication.

Many drug repurposing efforts have started with screening experiments, looking for drugs with certain properties.

Recently, researchers conducted a drug repurposing screening experiment for molecules that enhance a Parkinson’s protein (called GCase) and they found an interesting result: the antipsychotic medication quetiapine.

In today’s post, we will explain what GCase does, review what the new study found, and consider what could happen next.

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At the recent “Rallying to the Challenge” meeting (which was conducting in parallel with the Van Andel Institute‘s “Grand Challenges in Parkinson’s Disease“), I was asked by Cure Parkinson’s to present on why the biology surrounding genetic risk factors – like variation in the GBA and LRRK2 genes – are important targets for potential therapeutic intervention in Parkinson’s (my presentation starts at 2 hours & 10 minutes into the video above).

Specifically, I was asked to discuss why they are important targets not just for individuals carrying the genetic variations in these genes, but for the wider Parkinson’s community in general. And it is a good question.

How could inhibitors of LRRK2 or enhancers of GCase activity possibly be useful to individuals with idiopathic (spontaneous or not associated with a genetic risk factor) Parkinson’s?

My answer was rather simple.

What was it?

Continue reading “Making a (G)case for quetiapine” →

Monthly Research Review – September 2021

~ Simon ~ 3 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 September 2021.

The post is divided into 10 parts based on the type of research:

# # # #

So, what happened during September 2021?

In world news:

7th September – El Salvador becomes the first country in the world to accept Bitcoin as an official currency.

16th September – Inspiration4 launched by SpaceX becomes the first all-civilian spaceflight, carrying a four-person crew on a three-day orbit of the Earth.

21st September – A 10-foot wide house in Boston (known as “Skinny House”) sold for US$1.25 Million:

23rd September – Scientists report the discovery of human footprints in the state of New Mexico that are understood to be 23,000 years old, around the time of the last Ice Age – putting humans in North American significantly earlier than previously believed.

27th September – UK traffic was at its lowest for a Monday since England’s pandemic restrictions were lifted in mid-July, according to the data from the Office for National Statistics. Why? Because we do not have enough truck drivers to deliver the petrol. Nothing to do with BREXIT, the Government insisted, but the English were too busy making fun of themselves as they dealt with the crisis:

I particularly liked the way the BBC sent their journalist “Phil McCann” to report on the situation. I also rather liked:

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

In September 2021, there were 1,077 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (9,178for all of 2021 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 4 pieces of Parkinson’s news

Continue reading “Monthly Research Review – September 2021” →

When sonic hedgehog goes dyskinetic

~ Simon ~ 4 Comments

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Dyskinesias are involuntary muscle movements associated with long-term use of levodopa therapy (use of levodopa is not a certainty for developing dyskinesias, but there is an association). A better understanding of the underlying biology of dyskinesias is required in order to alleviate this condition for those affected by it.

Recently researchers have reported that an imbalance between dopamine levels (associated with levodopa treatment) and a protein called sonic hedgehog could be partly underlying the development of dyskinesias.

In today’s post, we will explore what sonic hedgehog does in the body, provide an overview of dyskinesias, review the new research, and discuss the implications of the research.

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The humble fly (Drosophila). Source: Ecolab

No one should ever be allowed to say that fly geneticists don’t have a sense of humour.

When it comes to the naming of genes, these guys are the best!

A gene is a section of DNA that provides the instructions for making a particular protein, and each gene has been given a name. Some names are just boring – such as leucine-rich repeat kinase 2 (or LRRK2) – while other names are rather amusing. Especially the fly genes.

For example, there is one fly gene called “indy”, which stands for I‘m Not Dead Yet. Flies with genetic variation in this gene have longer than average lifespans (Click here to read more about this):

Source: Sciencemag

Another amusingly named gene is “Cheap Date”. Flies with a genetic mutation in this gene are very susceptible to alcohol (Click here to read more about this):

Source: Lordsofthedrinks

There is also “Ken and Barbie” – genetic variations in this gene result in a lack of external genitalia (Click here to read more about this).

The fly research community have a lot of really great names for genes: “lunatic fringe”, “headcase” and “mothers against decapentaplegia (MAD)”. 

But one of the most popular gene names in all of biology is a gene called “Sonic Hedgehog”

What is Sonic Hedghog?

Continue reading “When sonic hedgehog goes dyskinetic” →

Because I’m all about that base

~ Simon ~ 2 Comments

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You may not realise it, but the DNA in your cells is under constant attack.

All kinds of stressors (like the damaging effects of oxidative stress resulting from cellular processes) are constantly bombarding this precision molecule that contains the genetic blueprint for making and maintaining you.

Luckily, millions of years of evolution has led to a complex and comprehensive DNA repair system that never takes holidays…. but might become a little slower as we age.

Recently researchers have reported that certain aspects of this DNA repair system could be playing a role in Parkinson’s. In today’s post, we will review some new research in this area and consider the implications of the findings. 

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My daughter is entering the pre-teen years, and I am struggling with all the horrors that that age brings.

Having survived the ‘Terrible Twos’ and the ‘Three-nager’ phase, I have absolutely adored innocence and magic of years 4 to 8. They were delightful. The ninth year, however, has brought with it the ominous arrival of (for lack of a better word) sass.

It has also involved a departure from the childhood songs (think Disney’s Lion King, Frozen, or Moana hits), and the introduction of more modern music, like her current favourite Meghan Trainor’s All about that Bass (see video above).

The next decade $£%#!& terrifies me.

But Meghan’s song provides an appropriate background for the subject matter of today’s post: Base excision repair

(Yeah, I know that’s a strange segway, but I’m tired and lacking imagination tonight)

What is Base excision repair?

Continue reading “Because I’m all about that base” →