Mind blowing modulation of mind

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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?

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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

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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

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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:

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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

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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

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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”

Monthly Research Review – August 2021

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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 August 2021.

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

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So, what happened during August 2021?

In world news:

August 6th – SpaceX stacked the Super Heavy Booster 4 and Star Ship 20 (Click here to read more about this)

 

August 9th – The Intergovernmental Panel on Climate Change releases the first part of its Sixth Assessment Report, which concludes that the effects of human-caused climate change are now “widespread, rapid, and intensifying“.

 

August 13th – Gino Strada passed away – and shame on you if you don’t know who he is

 

August 15th – The 50th anniversary of Nixon closing the “gold window” to foreign countries and ‘temporarily‘ abandoning the Bretton Woods Agreement, removing the gold standard and starting a new age of fiat currencies.

 

August 28th – The world’s northernmost island – a small patch of land measuring 60 x 30 metres – was announced by scientists off the coast of Greenland. The name Qeqertaq Avannarleq is proposed, which means “the northernmost island” (original!).

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

In August 2021, there were 765 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (8,101 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 4 pieces of Parkinson’s news

Continue reading “Monthly Research Review – August 2021”

When we talk about “disease modification”

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There is a lot of effort focused on developing therapies that are capable of “disease modification” in Parkinson’s…

…but what do we actually mean by this label?

In today’s post, we will explore the idea in more depth.

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Source: Martech

It is inconceivable, but we live in a world full of words that we don’t really know the meaning of.

For example: Travesty

For the longest time, I thought this word meant a tragedy or something very unfortunate. And I would use it in a sentence like “His death was such a travesty“. But it doesn’t mean tragic at all. Or even unfortunate. Rather, it refers to a mockery or parody; a distorted representation of something.

Another example is the word Peruse

I would use “peruse” in a sentence like “I am going into that bookshop to peruse the shelves“, because I thought that the word meant to skim or browse and that using it might make me sound erudite and sophisticated.

Source: BBC

But it doesn’t mean to skim or browse.

Peruse means to ‘examine or observe in depth“.

Similarly: Nauseous

I have often said “I feel nauseous“, but nauseous describes something that causes a feeling of nausea. It doesn’t refer to the feeling itself (The word nauseated means to be affected with nausea).

And at a recent session of bedtime story reading with my daughter, I noted on p.582 (first page of chapter 36) of the Harry Potter and the Goblet of fire, that Prof McGonagall ‘looked slightly nauseous‘. So I am not alone in making this mistake.

All of this leads me to the topic for today’s discussion: What do we actually mean by the words ‘disease modification’?

It is a label I use almost everyday with my job at Cure Parkinson’s, but it strikes me as one that we (everyone) don’t really fully grasp.

Ok, so what does disease modification mean to you?

Continue reading “When we talk about “disease modification””

RePOOPulating the gut

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The gastrointestinal system is teeming with life – billions and billions of microorganisms that play a critical role in not only your physiological wellbeing, but also your survival.

A lot of research has been conducted on how this biosphere changes as we age.

Recently researchers published a study indicating that transplantation of the gut bacteria from young mice can improve the brain and immune systems of aged mice.

In today’s post, we will explore how the bacteria in our guts affects us, review the new research, and consider the implication for Parkinson’s.

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Source: Youtube

Today’s post starts with goats.

In the late 1950s, the Australian Division of Tropical Pastures began introducing and evaluating tropical plants for use in the beef industry of Northern Australia. Among the most promising was a shrub from central and South America called Leucaena leucocephala (Leucaena).

Leucaena leucocephala. Source: Wikipedia

It looked like a winner – it grew like a weed and the cattle loved it – but there was just one small problem: Leucaena contains a toxic amino acid called “mimosine” which made the animals very sick.

I can imagine that the scientists involved with the introduction of Leucaena must have been thinking “Struth mate, I’m feeling like a fair dinkum, true blue drongo. What have we done?”

But one researcher – named Dr Raymond Jones – made an interesting observation while at a research meeting in Hawaii – goats on the island were eating Leucaena…. without getting sick.

Dr Raymond Jones. Source: Creation

Long story short, Dr Jones & colleagues worked out that a bacteria in the rumen (a special ‘stomach’ where the food is pre-digested by microbes in cattle, sheep and goats) of the animals in Hawaii was able to breakdown mimosine.

Subsequent transplantation of the bacteria (which was named Synergistes jonesii after Dr Jones) allowed goats and cattle in Australia to eat Leucaena, and they all lived happily ever after:

Title: Successful transfer of DHP-degrading bacteria from Hawaiian goats to Australian ruminants to overcome the toxicity of Leucaena.
Authors: Jones RJ, Megarrity RG.
Journal: Aust Vet J. 1986 Aug;63(8):259-62.
PMID: 3790013

This case represents a powerful example of how transplanting gut bacteria can result in positive outcomes.

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

Continue reading “RePOOPulating the gut”

Getting expansive about treg cells

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In cancer research, scientists have devised methods of extracting samples of blood from patients and then growing certain populations of cells in those samples. The isolated subpopulations  of cells can then be manipulated in cell culture, before they are then injected back into the patient.

This is a form of immunotherapy – artificially boosting the immune system to target specific disease-related pathology in the body.

Recently, researchers have been exploring this alternative form of immunotherapy in the context of Parkinson’s… with some interesting results.

In today’s post, we will look at review this new research and consider the implications in terms of future therapies for Parkinson’s.

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Source: lls

Some time back, a friend in oncology (cancer) research said to me that “we are about to cure all blood cancers“. It should be noted that this optimistic friend is a “glass is completely full” type.

How so?” I asked.

CAR T-cell technology is amazing. Really coming into bloom” they responded.

What is CAR T-cell technology?” I asked.

They explained that it is a kind of immunotherapy – a method of boosting the immune system to help us fight disease.

CAR T-cell approaches basically involve removing a sample of blood from a person with cancer, expanding specific populations of those cells in cell culture, genetically manipulating those cells, and then re-introducing them into the body. They also explained that there were lots of different versions of CAR T-cells, with all kinds of potential applications.

Cool” I said, sounding enthusiastic, but only half understanding what they were saying. My friend is an immunologist, and my summary here is a one sentence version of a 30 minute sermon.

But they are correct.

CAR T-cell technology is achieving really impressive results in cancer (Click here and here to read more about this topic).

Interesting. What does this have to do with Parkinson’s?

Continue reading “Getting expansive about treg cells”