Tagged: levodopa

Xenon: A bright light for dyskinesias?

A recent study published by French, British and Swiss researchers has grabbed the attention of some readers.

The report suggests that the inert/noble gas, Xenon, has powerful anti-dyskinetic properties in both mouse and primate models of Parkinson’s with L-DOPA-induced dyskinesias.

Dyskinesias are involuntary movements that can develop over time with prolonged used of L-DOPA treatments.

In today’s post, we will discuss what Xenon is, how it may be reducing dyskinesias, and we will consider some of the issues associated with using Xenon.


Dyskinesia. Source: JAMA Neurology

There is a normal course of events following a diagnosis of Parkinson’s.

Yes, I am grossly over-generalising, and no, I’m not talking from personal experience, but just go with me on this for the sake of discussion.

First comes the shock of the actual diagnosis. For many it is devastating news – an event that changes the course of their future. For others, however, the words ‘you have Parkinson’s‘ can provide a strange sense of relief that their current situation has a name and gives them something to focus on.

This initial phase is usually followed by the roller coaster of various emotions (including disbelief, sadness, anger, denial). It depends on each individual.

The emotional rollercoaster. Source: Asklatisha

And then comes the period during which many will try to familiarise themselves with their new situation. They will read books, search online for information, join Facebook groups (Click here for a good one), etc.

That search for information often leads to awareness of some of the realities of the condition.

And one potential reality that causes concern for many people (especially for people with early onset Parkinson’s) is dyskinesias.

What are dyskinesias?

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To B3 or not to B3, that is the question

The results of a recent clinical study for Parkinson’s conducted in Georgia (USA) has grabbed the attention of some readers.

The study involved Niacin (also known as nicotinic acid), which is a naturally occurring organic dietary compound and a form of vitamin B3.

The study was very small, but the researchers noticed something interesting in the blood of the participants: Niacin was apparently switching some of the immune cells from an inflammatory state to an anti-inflammatory state.

In today’s post, we will discuss what Niacin is, how it relates to Parkinson’s, and we will consider some of the issues with having too much niacin in your diet.


Source: Universal

It is one of the most common requests I get:

“Can you give an opinion on this supplement ____ or that vitamin ____ as a treatment for Parkinson’s?”

And I don’t like giving opinions, because (my standard disclosure) “I am not a clinician, just a research scientist. And even if i was a clinician, it would be unethical for me to comment as I am not familiar with each individual’s medical history. The best person to speak to is your personal doctor“.

But I also don’t like giving opinions because of a terrible fear that if I write anything remotely positive about anything remotely supplemental or vitamintal (is that a word?), a small portion of readers will rush off and gorge themselves on anything that sounds remotely similar to that supplement or vitamin.

So you will hopefully understand why I am hesitant to write this post.

But having said that, the recently published results of a small clinical study conducted in Augusta (Georgia, USA) are rather interesting.

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Is there NOP hope for Parkinson’s?

Please do not misread the title of this post!

Compounds targeting the Nociceptin receptor (or NOP) could provide the Parkinson’s community with novel treatment options in the not-too-distant future.

In pre-clinical models of Parkinson’s, compounds designed to block NOP have demonstrated neuroprotective properties, while drugs that stimulate NOP appear to be beneficial in reducing L-dopa induced dyskinesias. 

In today’s post we look at exactly what NOP is and what it does, we will review some of the Parkinson’s-based research that have been conducted so far, and we will look at what is happening in the clinic with regards to NOP-based treatments.


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Source: LUMS

On the surface of every cell in your body, there are lots of small proteins that are called receptors.

They are numerous and ubiquitous.

And they function act like a ‘light switch’ – allowing for certain biological processes to be initiated or inhibited. All a receptor requires to be activated (or blocked) is a chemical messenger – called a ligand – to come along and bind to it.

An example of a receptor on a cell. Source: Droualb

Each type of receptor has a particular structure, which is specific to certain shaped ligands (the chemical messenger I mentioned above). These ligands are floating around in the extracellular space (the world outside of the cell), having been released (or secreted) by other cells.

And this process represents one of the main methods by which cells communicate with each other.

By binding to a receptor, the ligand can either activate the receptor or alternatively block it. The activator ligands are called agonists, while the blockers are antagonists.

Agonists_and_antagonists

Agonist vs antagonist. Source: Psychonautwiki

Many of the drugs we currently have available in the clinic function in this manner.

For example, with Parkinson’s medications, some people will be taking Pramipexole (‘Mirapex’ and ‘Sifrol’) or Apomorphine (‘Apokyn’) to treat their symptoms. These drugs are Dopamine agonists because they bind to the dopamine receptors, and help with dopamine-mediated functions (dopamine being one of the chemicals that is severely in the Parkinsonian brain). As you can see in the image below the blue dopamine agonists can bypass the dopamine production process (which is reduced in Parkinson’s) and bind directly to the dopamine receptors on the cells that are the intended targets of dopamine.

Source: Bocsci

There are also dopamine antagonists (such as Olanzapine or ‘Zyprexa’) which blocks dopamine receptors. These drugs are not very helpful to Parkinson’s, but dopamine antagonist are commonly prescribed for people with schizophrenia.

Are there other receptors of interest in Parkinson’s?

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The anti-depressing research of antidepressants

Antidepressants are an important class of drugs in modern medicine, providing people with relief from the crippling effects of depression.

Recently, research has suggested that some of these drugs may also provide benefits to people suffering from Parkinson’s disease. But by saying this we are not talking about the depression that can sometimes be associated with this condition.

This new research suggests anti-depressants are actual providing neuroprotective benefits.

In today’s post we will discuss depression and its treatment, outline the recent research, and look at whether antidepressants could be useful for people with Parkinson’s disease.


Source: NatureWorldNews

It is estimated that 30 to 40% of people with Parkinson’s disease will suffer from some form of depression during the course of the condition, with 17% demonstrating major depression and 22% having minor depression (Click here to read more on this).

This is a very important issue for the Parkinson’s community.

Depression in Parkinson’s disease is associated with a variety of poor outcomes not only for the individuals, but also for their families/carers. These outcomes can include greater disability, less ability to care for oneself, faster disease progression, reduced cognitive performance, reduced adherence to treatment, worsening quality of life, and increased mortality. All of which causes higher levels of caregiver distress for those supporting the affected individual (Click here to read more about the impact of depression in early Parkinson’s).

What is depression?

Wikipedia defines depression as a “state of low mood and aversion to activity that can affect a person’s thoughts, behaviour, feelings, and sense of well-being” (Source). It is a common mental state that causes people to experience loss of interest or pleasure, feelings of guilt or low self-worth, disturbed sleep or appetite, low energy, and poor concentration.

Importantly, depression can vary significantly in severity, from simply causing a sense of melancholy to confining people to their beds.

Source: Prevention

What causes depression?

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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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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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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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Voyager Therapeutics: phase Ib clinical trial results

 

This week a biotech company called Voyager Therapeutics announced the results of their ongoing phase Ib clinical trial. The trial is investigating a gene therapy approach for people with severe Parkinson’s disease.

Gene therapy is a technique that involves inserting new DNA into a cell using a virus. The DNA can help the cell to produce beneficial proteins that go on help to alleviate the motor features of Parkinson’s disease.

In today’s post we will discuss gene therapy, review the new results and consider what they mean for the Parkinson’s community.


Source: Joshworth

On 25th August 2012, the Voyager 1 space craft became the first human-made object to exit our solar system.

After 35 years and 11 billion miles of travel, this explorer has finally left the heliosphere (which encompasses our solar system) and it has crossed into the a region of space called the heliosheath – the boundary area that separates our solar system from interstellar space. Next stop on the journey of Voyager 1 will be the Oort cloud, which it will reach in approximately 300 years and it will take the tiny craft about 30,000 years to pass through it.

Where is Voyager 1? Source: Tampabay

Where is Voyager actually going? Well, eventually it will pass within 1 light year of a star called AC +79 3888 (also known as Gliese 445), which lies 17.6 light-years from Earth. It will achieve this goal on a Tuesday afternoon in 40,000 years time.

Gliese 445 (circled). Source: Wikipedia

Remarkably, the Gliese 445 star itself is actually coming towards us. Rather rapidly as well. It is approaching with a current velocity of 119 km/sec – nearly 7 times as fast as Voyager 1 is travelling towards it (the current speed of the craft is 38,000 mph (61,000 km/h).

Interesting, but what does any of that have to do with Parkinson’s disease?

Well closer to home, another ‘Voyager’ is also ‘going boldly where no man has gone before’ (sort of).

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Self monitoring: there’s something in your eye

Self tracking/monitoring has become a popular habit for the general population with the introduction of products like Fitbit and Apple watch.

It is particularly useful for groups like the Parkinson’s community though, who are tired of having just one hour per year of assessments with their neurologist.

In today’s post, we will look at some new tracking/monitoring technologies that are being developed that could have important implications for not only how we assess Parkinson’s disease, but also for how we treat it.



Homo deus. Source: RealClearLife

I have recently finished reading ‘Homo Deus‘ by Yuval Noah Harari – the excellent follow-up to his previous book ‘Sapiens‘ (which is an absolute MUST READ!). The more recent book provides an utterly fascinating explanation of how we have come to be where we will be in the future (if that makes any sense).

In the final few chapters, Harari discusses many of the technologies that are currently under development which will change the world we live in (with a lot of interesting and cautionary sections on artificial intelligence – the machines that will know vastly more about us than we know about ourselves).

Of particular interest in this part of the book was a section on the Google-Novartis smart lens.

What is the Google-Novartis smart lens?

In 2014, a company called Alcon, which is a wholly owned subsidiary of Novartis formed a collaboration with the Google offshoot Verily Life Sciences that would focus on developing smart lens.

The initial project is rather ambitious: develop and take to the clinic a glucose-sensing contact lens for people with diabetes. The idea has been particularly championed by Google founder Sergey Brin (a prominent figure within the Parkinson’s community with his significant contributions to Parkinson’s research each year).

People with diabetes have to keep pricking their finger over the course of a day in order to check the levels of insulin in their blood. A less laborious approach would be welcomed by the diabetic world (an estimated 415 million people living with diabetes in the world).

This is what the lens may eventually look like:

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Helicobacter pylori: Unwanted passengers?

helicobacter-pylori


Whether we like it or not, we house a great deal of microbes.

Many of these tiny creatures aid us in our daily living by conducting important functions. Some of these microbes, however, may not be helping us, getting a free ride, and potentially causing trouble.

In today’s post we will review recent research regarding one particular family of bacteria, Helicobacter pylori, and what they might be doing in relations to Parkinson’s disease.


yong

Source: ScienceFriday

In his magnificent book, I contain multitudes, science writer/journalist Ed Yong writes that we – every single one of us – release approximately 37 million bacteria per hour. By talking, breathing, touching, or simply being present in the world, we are losing and also picking up the little passengers everywhere we go.

Reminds me of that Pascal Mercier book “Night Train to Lisbon” – We leave something of ourselves behind when we leave a place,… I’m not sure if this is what he was referring to though.

Yong also points out that: 80% of the bacteria on your right thumb are different to the bacteria on your left thumb.

It’s a fascinating book (and no, I am not receiving any royalties for saying that).

12-microbes.w710.h473.2x

Microbes. Source: NYmag

We have discussed microbes several times on this blog, particularly in the context of the gut and its connection to Parkinson’s disease (Click here, here and here to read some of those posts). Today we are going to re-visit one particular type of microbe that we have also discussed in a previous postHelicobacter pylori.

helicobacter-pylori-1

Helicobacter pylori. Source: Helico

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