Tagged: levodopa

Oleh Hornykiewicz (1926-2020)

# # # #

This week it was announced that Oleh Hornykiewicz had passed away.

I appreciate that most readers will not know who he is, but understand that his contribution to Parkinson’s research was important.

Not only was he instrumental in the discovery that dopamine is significantly reduced in the Parkinsonian brain, but he also demonstrated that levodopa treatment can help restore function.

In today’s post, we remember Oleh Hornykiewicz.

# # # #


It was sad to hear of the passing away of Oleh Hornykiewicz this week.

Most readers will have little clue as to who he was, but he played a very important role in the development of the Parkinson’s treatment we know of as levodopa therapy.

Very early in the 20th century, a chemical called dopamine was discovered, but no one really knew anything about it until a young Swedish research named Arvid Carlsson started to play with it.

Win 1113

Prof Arvid Carlsson. Source: Alchetron

In 1957, Carlsson discovered that when he injected a drug called reserpine into the brains of rabbits, the animals exhibited limited ability to move. He found that reserpine depleted levels of dopamine in the brains of the rabbits. He also discovered that by injecting the dopamine precursor – levodopa (more on this below) – into those same animals, he was able to rescue their motor ability. Importantly, he found that the precursor (called 5-hydroxytryptophan) to another chemical called serotonin, it was not capable of reversing the reduction in motor ability, indicating that the effect was specific to levodopa and dopamine.

He published this amazing result in the prestigeous scientific journal ‘Nature’:

avid

Title: 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists.
Authors: Carlsson A, Lindqvist M, Magnusson T.
Journal: Nature. 1957 Nov 30;180(4596):1200. No abstract available.
PMID: 13483658       (the article on the Nature website – access required)

This was a fantastic discovery.

But what to do with it?

And that is where an Austrian researcher named Oleh Hornykiewicz becomes part of the story.

Continue reading

Getting a GRP on dyskinesias

# # # #

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.

This week researchers reported that a single protein – called RasGRP1 – plays a central role in the development of dykinesias, raising hope that agents targeting this protein could identified and provide better quality of life of sufferers.

In today’s post, we will discuss what dyskinesias are and review the new research.

# # # #


 

 

Few people outside of the biomedical sciences may have heard of the Scripps Research Institute, but it is the largest private, not-for-profit medical research facility in the United States and among the largest in the world. It is headquartered in La Jolla, California but it has a sister facility in Jupiter, Florida.

Nice spot to do research. Source: Scripps

Collectively, “The Scripps” has 250 laboratories, which employs over 2,400 scientists, technicians, graduate students, and administrative staff.

It was founded in 1924 by journalist/philanthropist Ellen Browning Scripps.

Ellen Browning Scripps. Source: Lajollalight

The Scripps covers a wide variety of area in biomedical research, but this week a group of researcher led by scientists at the Florida Scripps institute published an interesting report on Parkinson’s:

Title: RasGRP1 is a causal factor in the development of l-DOPA–induced dyskinesia in Parkinson’s disease
Authors: Eshraghi M, Ramírez-Jarquín1 UM, Shahani1 N, Nuzzo T, De Rosa A, Swarnkar S, Galli N, Rivera O, Tsaprailis G, Scharager-Tapia C, Crynen G, Li Q, Thiolat ML, Bezard E, Usiello A, Subramaniam S
Journal: Science Advances, May 2020, 6, 18, eaaz7001
PMID: 32426479                 (This report is OPEN ACCESS if you would like to read it)

In this study, the researchers were interested in proteins that could be playing a major role in the development of dyskinesias.

What are dyskinesias?

Continue reading

Direct dopamine delivery

     

In the Parkinsonian brain, there is a severe reduction in a substance called dopamine. Reduced levels of this chemical are associated with the appearance of the motor features of Parkinson’s.

Dopamine replacement therapies has been the front line therapy for the condition for the last 50 years. But long-term use of drugs like L-dopa are associated with the rise of motor complications, like dyskinesias.

In the an effort to correct this, researchers in France have recently developed a method of continuously and directly delivering dopamine to the brain. They have now published the results of a study evaluating the safety and feasibility of this approach in a primate model of Parkinson’s.

In today’s post, we will discuss what dopamine is, review the results of this new research, and explore what might happen next for this new potential treatment method.

 


Prof David Devos. Source: Youtube

This is Dr David Devos.

He is Professor of medical pharmacology at University of Lille (France), world-renowned Parkinson’s researchers, a passionate advocate for the Parkinson’s community, and on top of all that he’s a really (and I mean REALLY) nice guy as well.

Recently, his research group (in collaboration with other scientists) published a report presenting a novel way of treating Parkinson’s, that he is now hoping to take to the clinic.

Here is the report:

Title: Intraventricular dopamine infusion alleviates motor symptoms in a primate model of Parkinson’s disease.
Authors: Moreau C, Rolland AS, Pioli E, Li Q, Odou P, Barthelemy C, Lannoy D, Demailly A, Carta N, Deramecourt V, Auger F, Kuchcinski G, Laloux C, Defebvre L, Bordet R, Duce J, Devedjian JC, Bezard E, Fisichella M, David D.
Journal: Neurobiol Dis. 2020 Mar 20:104846.
PMID: 32205254                    (This report is OPEN ACCESS if you would like to read it)

In this study, the researchers wanted to explore how to directly deliver a chemical called dopamine to the brain.

What is dopamine?

Continue reading

I’m worried about my IMM-AGE

 

Researchers have recently described a new method to quantify a person’s “immune age” – a measure that could act as a key determinant of future health, as well as response to disease and treatment.

This novel test appears to provide a more reliable predictor for the status of one’s immune system than any other previous method.

And it could be useful in other ways.

In today’s post, we will discuss this new method of determining “immune age”, explore examples of how similar analysis has been used for other conditions, and consider what it could mean for Parkinson’s.

 


Source: Emaze

Do you remember Andre Agassi?

I know he’s still around, but when I was young and less beautiful, I was a big fan. Not only of his on court achievements, but also of his charismatic off-court image.

And it certainly paid off well for him:

One of the things that Agassi taught us was that “image is everything”.

Before Agassi, tennis was a conservative sport of white shirts & shorts (McEnroe was basically as radical as things got). It was bland, conservative, and – yes, I’ll say it – boring.

Agassi not only brought colour but charisma to the game. It was shocking and disgraceful to some, but to young, naive fools like me, it was a captivating breath of much needed fresh air.

Source: Hesaidandshesaid

Despite the early infatuation with the stylings of Mr Agassi, I have to admit that I have never remotely been concerned about own image. My dimensions mean that I wear what fits as opposed to what I like, and as a result the finished product is better behind a keyboard rather than speaking to a crowd.

But as I have gotten older, I have become concerned about a different kind of IMM-AGE (not a typo).

Let me explain: Recently some researchers in Israel and at Stanford University in the US published a rather remarkable research report which if replicated could have important implications for how we approach medical care.

What did they report?

Continue reading

When disco-needs-ya, can gene therapy help ya?

 

With the recent announcement that the STEADY-PD III/Isradipine clinical trial did not reach its primary end point (that of slowing the progression of Parkinson’s), the winds of change have shifted with calls for a focus on biomarkers and better treatments, rather than disease modification.

Recently, researchers at Michigan State University have reported a novel experimental gene thearpy method for dealing with one of the most debilitating aspects of Parkinson’s – dyskinesias.

Ironically, their approach involves the same calcium channels that Isradipine blocks.

In today’s post, we will look at what dyskinesias are, what gene therapy is, and how this new approach could be useful for people currently burdened by these involutary movements.

 


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 (this is based on listening to a lot of people), 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 lives. 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 young/early onset Parkinson’s) is dyskinesias.

What are dyskinesias?

Continue reading

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?

Continue reading

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.

Continue reading

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.


4237_20160422175355

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?

Continue reading

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?

Continue reading

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?

Continue reading