Tagged: Parkinsons

Monitoring Parkinson’s: Let’s just sleep on it

Regular readers will be aware that here at the SoPD, we are on a mission to change the way we clinically test drugs (Click here for the most recent rant on this topic). 

We have a lot of interesting drugs waiting in the pipeline to be clinically tested and an eager (read: desperate) population of individuals affected by Parkinson’s, but we are missing one critical part of the equation: better tools of assessment.

How can we determine whether a drug is actually working or not? And how can we better monitor people over time on said drug?

Our current methods assessing individuals with Parkinson’s rely heavily on clinical rating scales and brain imaging. These are basic tools at best, conducted episodically (annually in general, or once every 2-6 months during a clinical trial), and provide little in the way of useful objective data (on an individual basis).

In today’s post, we will look at a single aspect of Parkinson’s – sleep – and try to nut-out a better/more informative method of assessing it over time.


The Bluesky project. Source: Mirror

Last week tech industry giants Pfizer and IBM made an big announcement.

It was news that I have been quietly waiting to hear for some time.

It related to their “BlueSky Project” – a collaboration between the two companies to provide better methods of assessment/monitoring of Parkinson’s.

 

The two companies announced that they are now ready to start accepting the first participants for a new clinical trial.

And it is a really intriguing study for one simple reason:

The entire trial will take place inside one house.

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DUBstop: Oxford-style

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This week multiple research groups at the University of Oxford and Boston-based FORMA Therapeutics announced a collaboration to identify, validate and develop deubiquitinating enzyme (DUB) inhibitors for the treatment of neurodegenerative conditions, like Parkinson’s.

But what exactly are DUB inhibitors? And how do they work?

In today’s post, we will answer these questions, look at what the new collaboration involves, and look at what else is happening with DUB inhibitors for Parkinson’s.


dubstep_color_and_white_by_dtfproductions-d3admfb

Source: Blog4dubstep

Dubstep is a genre of electronic dance music that originated in South London in the late 1990s. Only recently -in the 2010s – has the culture really become more mainstream. And while I have a hard time appreciating the heavy bass music (man, I am becoming a grumpy old man before my time), it is amazing to watch some of the dancers who robotically embody this form of music:

The guy on the right is named Marquese Scott. Sometimes he simply defies the laws of physics.

The title of today’s post is a play on words, because rather than doing ‘Dubstep’ we are going to be discussing how to ‘DUB-stop’.

Researchers in Oxford have recently signed an agreement with a US company to focus resources and attention on a new approach for tackling neurodegenerative conditions, including Parkinson’s.

What they are proposing is a complicated biological dance.

Their idea: to stop deubiquitinating (DUB) enzymes.

What are deubiquitinating enzymes?

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Planet Researcher to Planet Patient

Planet

This is Mariëtte Robijn:

photo

She’s really ‘leuk’ (Dutch for nice).

Diagnosed at 46 with Parkinson’s, Mariëtte keeps a great blog that touches on many areas of life, including boxing. But it also provides her with a medium to discuss how she lives with Parkinson’s (you should follow her if you don’t already).

In a recent post on her blog – called “Planet Patient vs Planet Researcher” – Mariëtte asks ‘are we really so very different, we patients and researchers?

Her answer is ‘Yes!‘ and she listed 10 areas where the differences are apparent.

Mariëtte’s points are made from an educated point of view – she is a very dedicated Parkinson’s research advocate.

Reading through her post, however, I saw it as a nice opportunity to provide the view of things from the other world (Planet Researcher). So, with her permission, I have copied her 10 points here and I have tried to provide a Planet Researcher view of her thoughts (below in red). And I should add that I do not speak for everyone on Planet Researcher – my views are simply that: mine.

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Monthly Research Review – April 2018

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 April 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and a new feature: Review articles/videos). 


So, what happened during April 2018?

In world news:

  • April 4–15th – The 2018 Commonwealth Games were held in Gold Coast, Queensland, Australia (New Zealand came 5th in the medals tally… not bragging, just saying).

Source: Vimeo

  • April 27th – Kim Jong-un crosses into South Korea to meet with President Moon Jae-in, becoming the first North Korean leader to cross the Demilitarised Zone since its creation in 1953. In initial small steps towards reconciliation, South Korea said it would remove loudspeakers that blare propaganda across the border, while North Korea said it would shift its clocks to align with its southern neighbour.

BFFs? Source: QZ

Source: Plus

  • And finally the city of Trier in Germany is already struggling to keep up with demand for ‘0-euro’ notes, bearing the face of its most famous son and communism’s creator Karl Marx. Sold for 3 euros each, the notes are part of celebrations for his 200th birthday (5th May 1818).

You get what you pay for. Source: DDR

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

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Could heart failure medication be good for Parkinson’s?

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

Recently, researchers in France have been exploring its use in Parkinson’s, and their results are really interesting.

‘Interesting’ because they not only point towards a clinically available drug that could (potentially) be repurposed for the treatments of Parkinson’s, but they also help to explain how our brains control movement.

In today’s post we will review the new results, discuss what they suggest about our ability to move, and we will look at efforts to take this drug to the clinic for Parkinson’s.


Source: Timemail

Heart failure (sometimes referred to as congestive heart failure) occurs when the heart is unable to pump sufficiently enough to maintain the required blood flow to meet the body’s needs. The most common causes of heart failure include coronary artery disease, high blood pressure, atrial fibrillation,valvular heart disease, and lifestyle issues (such as excess alcohol use). Overall around 2% of adults have heart failure; in those over the age of 65, this percentage increases to 6–10%. In 2015, it was estimated to affected approximately 40 million people worldwide (Source).

Common symptoms include:

  • shortness of breath
  • excessive tiredness
  • leg swelling.

A common treatment option for heart failure are diuretics.

What are diuretics?

Diuretics (sometimes called water pills) are medications that have been designed to increase the amount of water and salt expelled from the body as urine.

There are three types of diuretic medications. They are:

  • Thiazide
  • Loop
  • Potassium-sparing

Thiazide diuretics are the most commonly prescribed, generally for the treatment of high blood pressure. This class of drugs not only decreases the level of fluids in your body, they also cause your blood vessels to relax. Potassium-sparing diuretics reduce fluid levels in your body without – as the label suggests – causing you to lose potassium. The other types of diuretics can cause you to lose potassium, which can result in other health complications such as arrhythmia.

And then there are loop diuretics, which also decrease the level of fluid in the body.

But some loop diuretics have additional properties. And today we are going to have a look at one of them in the context of Parkinson’s.

It is called Bumetanide.

Why is Bumetanide interesting for Parkinson’s?

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Diabetes and Parkinson’s

A reader recently asked for an explanation of some recent research regarding diabetes and Parkinson’s.

You see, a significant proportion of the Parkinson’s community have glucose intolerance issues and some live with the added burden of diabetes. That said, the vast majority of diabetics do not develop PD. Likewise, the vast majority of people with Parkinson’s do not have a diagnosis of diabetes.

There does appear to be a curious relationship between Parkinson’s and diabetes, with some recent research suggests that this association can be detrimental to the course of the condition. 

In today’s post we will look at what what diabetes is, consider the associations with Parkinson’s, and we will discuss the new research findings.


Foreman and Ali. Source: Voanews

1974 was an amazing year.

On October 30th, the much-hyped heavyweight title match – the ‘Rumble in the Jungle’ – between George Foreman and Muhammad Ali took place in Kinshasa, Zaire (Democratic Republic of the Congo).

Stephen King. Source: VanityFair

A 26-year-old author named Stephen King published his debut novel, “Carrie” (April 5, with a first print-run of just 30,000 copies).

Lucy. Source: Youtube

The fossil remains of a 3.2 million years old hominid skeleton was discovered in Ethiopia (November 24th). It was named ‘Lucy’ – after the song “Lucy in the Sky with Diamonds” by The Beatles which was played repeatedly in the expedition camp the evening after the team’s first day of work on the site (Source).

And Richard Nixon becomes the first US president to resign from office (August 9th).

President Richard Nixon. Source: Fee

In addition to all of this, in December of 1974, a small study was published in the Journal of Chronic Diseases.

It dealt with Parkinson’s and it presented a rather startling set of findings:

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The aggregating antics of (some) anaesthetics

This is one of those posts that I am reluctant to write because there is the very real possibility of it being taken out of context and causing someone to panic. But several readers have asked me to address a new piece of research that was published this week which has them concerned.

Anaesthetics are very useful agents in medicine, but they have long been known to have biological effects beyond simply numbing/sedating individuals. Some of those effects are beneficial, while others….mmm, not so beneficial. And the new research published this week leans towards the latter: Certain anaesthetics apparently induce mutant protein aggregation in neurons and cause stress responses in those brain cells.

In today’s post, we will discuss what anaesthetics are, how (we think) they work, and what the results of this new research actually mean.


William Morton’s first public demonstration. Source: Pinterest

On Friday 16th October 1846, history was made.

On that date, an American dentist named William T. G. Morton (1819-1868) made the first public demonstration of the use of inhaled ether as a surgical anaesthetic.

William Morton. Source: Wikipedia

At this demonstration Dr. John Collins Warren painlessly removed a tumor from the neck of a Mr. Edward Gilbert Abbott. After finishing the operation and Abbott had regained consciousness, Warren asked Abbott how he felt.

John Collins Warren. Source: General-anaesthesia

Abbott replied, “Feels as if my neck’s been scratched.”

Warren then turned to the medical audience and said:

“Gentlemen, this is no Humbug”

This was an obvious shot at an unsuccessful demonstration of nitrous oxide as a anaesthesia the year before (by Horace Wells in the same theatre), which ended with the audience shouting “Humbug!” after they heard the patient groaning with pain during the procedure.

The important thing to appreciate here is the magnitude of Morton’s achievement within in the history of medicine.

Before 16th October 1846, surgical procedures were not very pleasant affairs.

After 16th October 1846,… well, to be honest, they are still not very pleasant affairs, but at least the patient can skip most of the painful parts of an operation.

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

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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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Objective measures: Getting smart about pills

There has been a lot of discussion on this site (and elsewhere on the web) regarding the need for more objective systems of measuring Parkinson’s – particularly in the setting of clinical trials.

Yes, subjective reports of patient experience are important, but they can easily be biased by ‘placebo responses’.

Thus, measures that are beyond the clinical trial participants conscious control – and focused on biological outcomes – are needed. 

In today’s post, we will consider one possible approach: Smart pills. We will discuss what they are, how they work, and how they could be applied to Parkinson’s research.


Source: Chicagotribune

In order to encourage a growing discussion regarding objective measures of Parkinson’s (and to follow up on previous rants – Click here and here for examples), I have decided to regularly (once a month) highlight new technologies that could provide the sort of unbiased methods of data collection that are required for assessing whether a treatment is having an impact on Parkinson’s.

Today, we will look at smart pills.

What is a smart pill?

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Something is interesting in the state of Denmark

 

 

Gaucher disease is a genetic disorder caused by the reduced activity of an enzyme, glucocerebrosidase. This enzyme is produced by a region of DNA (or a gene) called GBA – the same GBA gene associated with a particular form of Parkinson’s.

Recently, a Danish company has been testing a new drug that could benefit people with Gaucher disease.

It is only natural to ask the question: Could this drug also benefit GBA-associated Parkinson’s?

In today’s post, we will discuss what Gaucher disease is, how this experimental drug works, and why it would be interesting to test it in Parkinson’s.


Will Shakespeare. Source: Ppolskieradio

The title of this post is a play on words from one of the many famous lines of William Shakespeare’s play, Hamlet.

The original line – delivered by Marcellus (a Danish army sentinel) after the ghost of the dead king appears – reads: If the authorities knew about the problems and chose not to prevent them, then clearly something is rotten in the state of Denmark.

(Act 1, Scene 4)

The title of this post, however, is: Something is interesting in the state of Denmark

This slight change was made because certain Danish authorities know about the problem and they are trying to prevent it. The ‘authorities’ in this situation are some research scientists at a biotech company in Denmark, called Orphazyme.

And the problem is Parkinson’s?

No, the problem is Gaucher disease.

Huh? What is Gaucher disease?

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