Tagged: research

Resveratrol’s neglected siblings

 

We have previously discussed the powerful antioxidant Resveratrol, and reviewed the research suggesting that it could be beneficial in the context of Parkinson’s disease (Click here to read that post).

I have subsequently been asked by several readers to provide a critique of the Parkinson’s-associated research focused on Resveratrol’s twin sister, Pterostilbene (pronounced ‘Terra-still-bean’).

But quite frankly, I can’t.

Why? Because there is NO peer-reviewed scientific research on Pterostilbene in models of Parkinson’s disease.

In today’s post we will look at what Pterostilbene is, what is known about it, and why we should seriously consider doing some research on this compound (and its cousin Piceatannol) in the context of Parkinson’s disease.


Blue berries are the best natural source of Pterostilbene. Source: Pennington

So this is likely to be the shortest post in SoPD history.

Why?

Because there is nothing to talk about.

There is simply no Parkinson’s-related research on the topic of today’s post: Pterostilbene. And that is actually a crying shame, because it is a very interesting compound.

What is Pterostilbene?

Like Resveratrol, Pterostilbene is a stilbenoid.

Stilbenoids are a large class of compounds that share the basic chemical structure of C6-C2-C6:

Resveratrol is a good example of a stilbenoid. Source: Wikipedia

Stilbenoids are phytoalexins (think: plant antibiotics) produced naturally by numerous plants. They are small compounds that become active when the plant is under attack by pathogens, such as bacteria or fungi. Thus, their function is generally considered to part of an anti-microbial/anti-bacterial plant defence system for plants.

The most well-known stilbenoid is resveratrol which grabbed the attention of the research community in a 1997 study when it was found to inhibit tumour growth in particular animal models of cancer:

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Trying to ‘beet’ Parkinson’s in the developing world

Recently I discussed my ‘Plan B’ idea, which involves providing a cheap alternative to expensive drugs for folks living in the developing world with Parkinson’s (Click here for that post).

While doing some research for that particular post, I came across another really interesting bit of science that is being funded by Parkinson’s UK.

It involves Beetroot.

In today’s post we will look at how scientists are attempting turn this red root vegetable into a white root vegetable in an effort to solve Parkinson’s in the developing world.


Pompeii and Mount Vesuvius. Source: NationalGeo

During visits to the ancient Roman city of Pompeii (in Italy), tourists are often drawn by their innocent curiosity to the ‘red light’ district of the city. And while they are there, they are usually amused by the ‘descriptive’ murals that still line the walls of the buildings in that quarter.

So amused in fact that they often miss the beetroots.

Huh? Beetroots?

Yes, beetroots.

I’m not suggesting that anyone spends a great deal of time making a close inspection of the walls, but if you look very carefully, you will often see renditions of beetroots.

They are everywhere. For example:

Two beetroots hanging from the ceiling.

Again: Huh?

The Romans considered beetroot to be quite the aphrodisiac, believing that the juice ‘promoted amorous feelings’. They also ate the red roots for medicinal purposes, consuming it as a laxative or to cure fever.

And this medicinal angle lets me segway nicely into the actual topic of today’s post. You see, in the modern era researcher are hoping to use beetroot for medicinal purposes again. But this time, the beetroot will be used to solve an issue close to my heart: treating people with Parkinson’s in the developing world.

Using beetroot to treat Parkinson’s?

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A clever new Trk for Rasagiline

The protein Alpha Synuclein has long been considered the bad-boy of Parkinson’s disease research. Possibly one of the main villains in the whole scheme of things. 

New research suggests that it may be interfering with a neuroprotective pathway, leaving the affected cell more vulnerable to stress/toxins. But that same research has highlighted a novel beneficial feature of an old class of drugs: MAO-B inhibitors.

In today’s post we will outline the new research, discuss the results, and look at whether this new Trk warrants a re-think of MAO-B inhibitors.


The great Harry Houdini. Source: Wikipedia

I’m not sure about you, but I enjoy a good magic trick.

That exhilarating moment when you are left wondering just one thing: How do they do that?

(Seriously, at 4:40 a baguette comes out of thin air – how did he do that?)

Widely believed to have been one of the greatest magicians of all time (Source), Harry Houdini is still to this day revered among those who practise the ‘dark arts’.

Born Erik Weisz in Budapest (in 1874), Houdini arrived in the US in 1878. Fascinated with magic, in 1894, he launched his career as a professional magician and drew attention for his daring feats of escape. He renamed himself “Harry Houdini” – the first name being derived from his childhood nickname, “Ehrie,” and the last name paying homage to the great French magician Jean Eugène Robert-Houdin. In 1899, Houdini’s act caught the eye of Martin Beck, an entertainment manager, and from there the rest is history. Constantly upping the ante, his feats became bolder and more death defying.

And the crowds loved him.

From stage, he moved on to film – ultimately starting his own production company, Houdini Picture Corporation. In addition, he was a passionate debunker of psychics and mediums, his training in magic helping him to expose frauds (which turned him against his former friend Sir Arthur Conan Doyle, who believed deeply in spiritualism).

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

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NIX-ing the PARKIN and PINK1 problem

In American slang, to ‘nix‘ something is to ‘put an end to it’.

Curiously, a protein called NIX may be about to help us put an end to Parkinson’s disease, at least in people with specific genetic mutations.

In today’s post we will look at what NIX is, outline a new discovery about it, and discuss what this new information will mean for people living with Parkinson’s disease.


Sydney harbour. Source: uk.Sydney

Before we start, I would like the reader to appreciate that I am putting trans-Tasman rivalry side here to acknowledge some really interesting research that is being conducted in Australia at the moment.

And this is really interesting.

I have previously spoken a lot about mitochondria and Parkinson’s on this website. For the uninitiated, mitochondria are the power house of each cell. They help to keep the lights on. Without them, the party is over and the cell dies.

Mitochondria

Mitochondria and their location in the cell. Source: NCBI

You may remember from high school biology class that mitochondria are tiny bean-shaped objects within the cell. They convert nutrients from food into Adenosine Triphosphate (or ATP). ATP is the fuel which cells run on. Given their critical role in energy supply, mitochondria are plentiful (some cells have thousands) and highly organised within the cell, being moved around to wherever they are needed.

Like you and I and all other things in life, however, mitochondria have a use-by date.

As mitochondria get old and worn out (or damaged) with time, the cell will recycle them via a process called mitophagy (a blending of the words mitochondria and autophagy – the waste disposal system of each cell).

What does this have to do with Parkinson’s disease?

Well, about 10% of Parkinson’s cases are associated with particular genetic variations that render people vulnerable to developing the condition. Some of these mutations are in sections of DNA (called genes) that provide the instructions for proteins that are involved in the process of mitophagy. Two genes, in particular, are the focus of a lot of Parkinson’s-related research – they are called PARKIN and PINK1.

What do PARKIN and PINK1 do?

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We need a clinical trial of broccoli. Seriously!

In a recent post, I discussed research looking at foods that can influence the progression of Parkinson’s (see that post here). I am regularly asked about the topic of food and will endeavour to highlight more research along this line in future post.

In accordance with that statement, today we are going to discuss Cruciferous vegetables, and why we need a clinical trial of broccoli.

I’m not kidding.

There is growing research that a key component of broccoli and other cruciferous vegetables – called Glucoraphanin – could have beneficial effects on Parkinson’s disease. In today’s post, we will discuss what Glucoraphanin is, look at the research that has been conducted and consider why a clinical trial of broccoli would be a good thing for Parkinson’s disease.


 

Cruciferous vegetables. Source: Diagnosisdiet

Like most kids, when I was young I hated broccoli.

Man, I hated it. With such a passion!

Usually they were boiled or steamed to the point at which they have little or no nutritional value, and they largely became mush upon contact with my fork.

The stuff of my childhood nightmares. Source: Modernpaleo

As I have matured (my wife might debate that statement), my opinion has changed and I have come to appreciate broccoli. Our relationship has definitely improved.

In fact, I have developed a deep appreciation for all cruciferous vegetables.

And yeah, I know what you are going to ask:

What are cruciferous vegetables?

Cruciferous vegetables are vegetables of the Brassicaceae family (also called Cruciferae). They are a family of flowering plants commonly known as the mustards, the crucifers, or simply the cabbage family. They include cauliflower, cabbage, garden cress, bok choy, broccoli, brussels sprouts and similar green leaf vegetables.

Cruciferous vegetables. Source: Thetherapyshare

So what have Cruciferous vegetables got to do with Parkinson’s?

Well, it’s not the vegetables as such that are important. Rather, it is a particular chemical that this family of plants share – called Glucoraphanin – that is key.

What is Glucoraphanin?

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Plan B: Itchy velvet beans – Mucuna pruriens

Mucuna-Pruriens-Mood-and-Hormone-Velvet-Bean

The motor features of Parkinson’s disease can be managed with treatments that replace the chemical dopamine in the brain. 

While there are many medically approved dopamine replacement drugs available for people affected by Parkinson’s disease, there also are more natural sources.

In today’s post we will look at the science and discuss the research supporting one of the most potent natural source for dopamine replacement treatment: Mucuna pruriens


Plan.B-oneway

Source: Yourtimeladies

When asked by colleagues and friends what is my ‘plan B’ (that is, if the career in academia does not play out – which is highly probable I might add – Click here to read more about the disastrous state of biomedical research careers), I answer that I have often considered throwing it all in and setting up a not-for-profit, non-governmental organisation to grow plantations of a tropical legume in strategic places around the world, which would provide the third-world with a cheap source of levodopa – the main treatment in the fight against Parkinson’s disease.

Mucuna_pruriens_08

Plan B: A legume plantation. Source: Tropicalforages

The response to my answer is generally one of silent wonder – that is: me silently wondering if they think I’m crazy, and them silently wondering what on earth I’m talking about.

As romantic as the concept sounds, there is an element of truth to my Plan B idea.

I have read many news stories and journal articles about the lack of treatment options for those people with Parkinson’s disease living in the developing world.

South-Africa-hospital

Hospital facilities in the rural Africa. Source: ParkinsonsLife

Some of the research articles on this topic provide a terribly stark image of the contrast between people suffering from Parkinson’s disease in the developing world versus the modernised world. A fantastic example of this research is the work being done by the dedicated researchers at the Parkinson Institute in Milan (Italy), who have been conducting the “Parkinson’s disease in Africa collaboration project”.

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The researchers at the Parkinson Institute in Milan. Source: Parkinson Institute 

The project is an assessment of the socio-demographic, epidemiological, clinical features and genetic causes of Parkinson’s disease in people attending the neurology out-patients clinic of the Korle Bu Teaching and Comboni hospitals. Their work has resulted in several really interesting research reports, such as this one:

Ghana
Title: The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa.
Authors: Cilia R, Akpalu A, Sarfo FS, Cham M, Amboni M, Cereda E, Fabbri M, Adjei P, Akassi J, Bonetti A, Pezzoli G.
Journal: Brain. 2014 Oct;137(Pt 10):2731-42.
PMID: 25034897          (This article is OPEN ACCESS if you would like to read it)

In this study, the researchers collected data in Ghana between December 2008 and November 2012, and each subject was followed-up for at least 6 months after the initiation of Levodopa therapy. In total, 91 Ghanaians were diagnosed with Parkinson’s disease (58 males, average age at onset 60 ± 11 years), and they were compared to 2282 Italian people with Parkinson’s disease who were recruited during the same period. In long-term follow up, 32 Ghanaians with Parkinson’s disease were assessed (with an average follow period of 2.6 years).

There are some interesting details in the results of the study, such as:

  • Although Levodopa therapy was generally delayed – due to availability and affordability – in Ghana (average disease duration before Levodopa treatment was 4.2 years in Ghana versus just 2.4 years in Italy), the actual disease duration – as determined by the occurrence of motor fluctuations and the onset of dyskinesias – was similar in the two populations.

Ghana2

Source: PMC

  • The motor fluctuations were similar in the two populations, with a slightly lower risk of dyskinesias in Ghanaians.
  • Levodopa daily doses were higher in Italians, but this difference was no longer significant after adjusting for body weight.
  • Ghanaian Parkinson’s sufferers who developed dyskinesias were younger at onset than those who did not.

Reading these sorts of research reports, I am often left baffled by the modern business world’s approach to medicine. I am also left wondering how an individual’s experience of Parkinson’s disease in some of these developing nations would be improved if a cheap alternative to the dopamine replacement therapies was available.

Are any cheap alternatives available?

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AAV-PHP.B: The future is apparently now

In addition to looking at current Parkinson’s disease research on this website, I like to look at where technological advances are taking us with regards to future therapies.

In July of this year, I wrote about a new class of engineered viruses that could potentially allow us to treat conditions like Parkinson’s disease using a non-invasive, gene therapy approach (Click here to read that post). At the time I considered this technology way off at some point in the distant future. Blue sky research. “Let’s wait and see” – sort of thing.

So imagine my surprise when an Italian research group last weekend published a new research report in which they used this futurist technology to correct a mouse model of Parkinson’s disease. Suddenly the distant future is feeling not so ‘distant’.

In today’s post we will review and discuss the results, and look at what happens next.


Technological progress – looking inside the brain. Source: Digitial Trends

I have said several times in the past that the pace of Parkinson’s disease research at the moment is overwhelming.

So much is happening so quickly that it is quite simply difficult to keep up. Not just here on the blog, but also with regards to the ever increasing number of research articles in the “need to read” pile on my desk. It’s mad. It’s crazy. Just as I manage to digest something new from one area of research, two or three other publications pop up in different areas.

But it is the shear speed with which things are moving now in the field of Parkinson’s research that is really mind boggling!

Source: Pinterest

Take for example the case of Squalamine.

In February of this year, researchers published an article outlining how a drug derived from the spiny dogfish could completely suppress the toxic effect of the Parkinson’s associated protein Alpha Synuclein (Click here to read that post).

The humble dogfish. Source: Discovery

And then in May (JUST 3 MONTHS LATER!!!), a biotech company called Enterin Inc. announced that they had just enrolled their first patient in the RASMET study: a Phase 1/2a randomised, controlled, multi-center clinical study evaluating a synthetic version of squalamine (called MSI-1436) in people with Parkinson’s disease. The study will enrol 50 patients over a 9-to-12-month period (Click here for the press release).

Source: Onemednews

Wow! That is fast.

Yeah, I thought so too, but then this last weekend a group in Italy published new research that completely changed my ideas on the meaning of the word ‘fast’. Regular readers will recall that in July I discussed amazing new technology that may one day allow us to inject a virus into a person’s arm and then that virus will make it’s way up to the brain and only infect the cells that we want to have a treatment delivered to. This represents non-invasive (as no surgery is required), gene therapy (correcting a medical condition with the delivery of DNA rather than medication). This new study used the same virus we discussed in July.

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O’mice an’ men – gang aft agley

This week a group of scientists have published an article which indicates differences between mice and human beings, calling into question the use of these mice in Parkinson’s disease research.

The results could explain way mice do not get Parkinson’s disease, and they may also partly explain why humans do.

In today’s post we will outline the new research, discuss the results, and look at whether Levodopa treatment may (or may not) be a problem.


The humble lab mouse. Source: PBS

Much of our understanding of modern biology is derived from the “lower organisms”.

From yeast to snails (there is a post coming shortly on a snail model of Parkinson’s disease – I kid you not) and from flies to mice, a great deal of what we know about basic biology comes from experimentation on these creatures. So much in fact that many of our current ideas about neurodegenerative diseases result from modelling those conditions in these creatures.

Now say what you like about the ethics and morality of this approach, these organisms have been useful until now. And I say ‘until now’ because an interesting research report was released this week which may call into question much of the knowledge we have from the modelling of Parkinson’s disease is these creatures.

You see, here’s the thing: Flies don’t naturally develop Parkinson’s disease.

Nor do mice. Or snails.

Or yeast for that matter.

So we are forcing a very un-natural state upon the biology of these creatures and then studying the response/effect. Which could be giving us strange results that don’t necessarily apply to human beings. And this may explain our long history of failed clinical trials.

We work with the best tools we have, but it those tools are flawed…

What did the new research report find?

This is the study:


Title: Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease
Authors: Burbulla LF, Song P, Mazzulli JR, Zampese E, Wong YC, Jeon S, Santos DP, Blanz J, Obermaier CD, Strojny C, Savas JN, Kiskinis E, Zhuang X, Krüger R, Surmeier DJ, Krainc D
Journal: Science, 07 Sept 2017 – Early online publication
PMID: 28882997

The researchers who conducted this study began by growing dopamine neurons – a type of cell badly affected by Parkinson’s disease – from induced pluripotent stem (IPS) cells.

What are induced pluripotent stem cells?

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QUATS going on?!?

BE WARNED: THIS POST MIGHT UPSET SOME READERS

A recently published research report has caused a bit of a fuss in the media, and I have been contacted by a lot of concerned readers regarding this particular study.

It deals with some chemicals – which can be found in everyday products – that may be having a negative effect on biological processes that are related to Parkinson’s disease – specifically, the normal functioning of the mitochondria (the power stations of each cell).

In today’s post we will discuss the new research, what the chemicals do, and whether the Parkinson’s community should be concerned.


Source: Sacramentodentistry

Toothpaste.

It is something that most of us take completely for granted in the modern world. A product that sits in our bathroom, by the sink or on a shelf, and 2-3 times per day we stick some of it in our mouth and brush it around a bit. Given the well ingrained habit of repetitively ingesting of the stuff, we have little trouble with the idea of switching brands or trying new variations (“Oooh look, this one will make your teeth whiter. Let’s try it”).

I mean, come on – it’s just toothpaste. It’s safe, right?

It probably won’t surprise many of you to learn that the composition of toothpaste has changed quite a bit over the years, but what might amaze you is just how many years are involved with that statement: 

Egyptian toothbrush. Source: Nathanpaarth

The Egyptians recognised the importance of looking after one’s teeth at a very early stage. Apparently they had a lot of trouble with their teeth because their bread had grit in it which wore away their enamel. As far back as 5000BC, they had a form of toothpaste that they used to clean their teeth. It was a mix of powdered ashes of ox hooves, myrrh, powdered and burnt eggshells, and pumice (Source: Wikipedia). The Greeks, followed by the Romans, improved on the recipes (by adding abrasive ingredients such as crushed bones and oyster shells – delightful, huh?), but it wasn’t until after World War I that the modern day pre-mixed toothpastes became popular.

The cavity fighting chemical, Fluoride, was first added to toothpastes in the 1890s, and in 1908 Newell Sill Jenkins (an American dentist) invented the first toothpaste that contained disinfectants. It was called Kolynos (from the Greek words Kolyo nosos (κωλύω νόσος), meaning “disease prevention”). 

Source: Flickr

Following the advent of Kolynos, most toothpaste companies added antiseptic and disinfectant agents to improve the quality and effectiveness of their product. Being offered a tooth cleaning product with magical antibiotic properties seemed to reassure consumers that they were buying something that might actually work. And this led to more and more chemicals being added to toothpaste. Such additions included chemical like triclosan, cetylpyridinium chloride and benzalkonium chloride.

These chemicals are safe though…right?

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Hey DJ, I-so-sit-rate!

The title of this post probably reads like the mad, drug-fuelled scream of a drunk Saturday night party animal, but the elements of it may be VERY important for a particular kind of Parkinson’s disease.

Mutations in a gene called DJ-1 can cause an early onset form of Parkinson’s disease. The protein of DJ-1 plays an important role in how cells handle oxidative stress – or the increase in damaging free radicals (explained below).

This week researchers announced that they have found an interesting new therapeutic target for people with DJ-1 associated Parkinson’s disease: A chemical called Isocitrate.

In this post, we will discuss what DJ-1 is involved with Parkinson’s disease, how isocitrate helps the situation, and what the results of new research mean for future therapeutic strategies.


original-26772-1364707371-8

Source: Listchallenge

In 2017, we are not only observing the 200 year anniversary of the first description of Parkinson’s disease (by one Mr James Parkinson), but also the 20th anniversary of the discovery of the first genetic variation associated with the condition (Click here to read more about that). Our understanding of the genetics of Parkinson’s disease since 1997, has revolutionised the way we look at Parkinson’s disease and opened new doors that have aided us in our understanding.

During the last 20 years, we have identified numerous sections of DNA (these regions are called genes) where small errors in the genetic coding (mutations or variants) can result in an increased risk of developing Parkinson’s disease. As the graph below indicates, mutations in some of these genes are very rare, but infer a very high risk, while others are quite common but have a low risk of Parkinson’s disease.

The genetics of PD. Source: Journal of Parkinson’s disease

Some of the genetic mutation need to be provided by both the parents for Parkinson’s to develop (an ‘autosomal recessive‘ mutation – the yellow circles in the graph above); while in other cases the genetic variant needs only to be provided by one of the parents (an ‘autosomal dominant’ mutation – the blue circles). Many of the genetic mutations are very common and simply considered a region of increased risk (green circles).

Importantly, all of these genes provide the instructions for making a protein – which are the functional parts in a cell. And each of these proteins have specific roles in biological processes. These functions tell us a little bit about how Parkinson’s disease may be working. Each of them is a piece of the jigsaw puzzle that we are trying to finish. As you can see in the image below, many of the genes mentioned in the graph above give rise to proteins that are involved in different parts of the process of autophagy – or the waste disposal system of the cell. You may notice that some proteins, like SCNA (otherwise known as alpha synuclein), are involved in multiple steps in this process.

The process of autophagy. Source: Nature

In today’s post we are going to look at new research regarding just one of these genes/proteins. It is called DJ-1, also known as Parkinson disease protein 7 (or PARK7).

What is DJ-1?

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