Tag: calcium

Isradipine: Posthoc analysis

~ Simon ~ 4 Comments

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Last year the results of the large STEADY-PD study were published. The investigators behind the Phase III clinical trial reported that the experimental treatment being tested had no effect on the progression of Parkinson’s in recently diagnosed individuals.

The treatment being evaluated was a calcium channel blocker called isradipine – it is used for treating high blood pressure.

Since publishing the results, some of the researchers behind the study have been conducting post hoc analysis of the data… and they have found something interesting: An effect.

In today’s post, we will look at why isradipine was evaluated in Parkinson’s, what the results of the STEADY-PD study were, and what the newly discovered effect could mean.

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Source: Medium

In the scientific world, post hoc analysis (from the Latin post hoc, meaning “after this”) consists of statistical analyses that are specified after the data has been seen. This type of analysis should only be considered for “hypothesis forming” exercises, and not be viewed as cherry-picking of the data in order to find an effect. 

And one must be careful with interpretation of data (eg. most people who are involved in car crashes have been reported as wearing clothes at the time of the incident, thus we should get rid of clothes to assess if this will reduce the incidence of automobile accidents).

Post hoc analyses of completed clinical trial data, however, can be very useful process of identifying interesting trends that could be explored in future studies.

A good example of this has recently been conducted on the STEADY-PD clinical trial study.

What was the STEADY-PD clinical trial about?

Continue reading “Isradipine: Posthoc analysis” →

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

~ Simon ~ 4 Comments

 

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 “When disco-needs-ya, can gene therapy help ya?” →

Parkinson’s: When evolution leaves parts of us behind?

~ Simon ~ 13 Comments

 

Recently researchers have proposed an interesting idea for why Parkinson’s is a distinctly human condition: There are parts of our brains that have not kept up with evolution, and as we live longer those areas become strained which ultimately results in the features of Parkinson’s.

It’s a really interesting idea – one which could have major implications.

In today’s post, we will review the new proposal and consider how we could use it in our approach to therapeutic interventions.

 

2020 Tesla Roadster. Source: Motortrend

By nature and design, I am not a car person.

If I can actually fit in the car (I am rather tall) and it gets me from A to B, it’s a great car. I don’t really care what it looks like, because I usually look ridiculous in the more sporty versions (my knees up around my ears…). As long as it gets from A to B, I’m happy.

Having said that, I do appreciate the technological advancements that are being made by companies like Tesla (I mean seriously, their Roadster – pictured above – is an electric car that does 0-60 mph in 1.9-seconds, quarter-mile in less than 9-second, a 250-plus-mph top speed, and an all-electric range of 620-mile! All of those statistics are incredible!).

It is amazing the evolutionary process that automobiles have gone through.

The first petrol engine-propelled car invented by Karl Benz. Source: Oxfordsurfaces

Every aspect of these vehicles has changed over time. From the wheels to the engine and from petrol to electric based cars, each component has been adapted across the decades to keep up with the needs of its environment.

Researchers are now wondering if the same can be said for our brains. And just recently some scientists have questioned whether some evolutionary design faults could explain why humans develop Parkinson’s.

What?!? What do you mean?

Continue reading “Parkinson’s: When evolution leaves parts of us behind?” →

I’ll have the fish please

~ Simon ~ 16 Comments

We have previously discussed the importance of the right foods for people with Parkinson’s on this blog – Click here for a good example.

Recently, new data from researchers in Sweden points towards the benefits of a specific component of fish in particular.

It is a protein called β-parvalbumin, which has some very interesting properties.

In today’s post, we discuss what beta-parvalbumin is, review the new research findings, and consider how this new information could be applied to Parkinson’s.

A very old jaw bone. Source: Phys

In 2003, researchers found 34 bone fragments belonging to a single individual in a cave near Tianyuan, close to Beijing (China).

But it was not the beginning of a potential murder investigation.

No, no.

This was the start of something far more interesting.

Naming the individual “Tianyuan man”, the researchers have subsequently found that “many present-day Asians and Native Americans” are genetically related to this individual. His bones represented one of the oldest set of modern human remains ever found in the eastern Eurasia region.

Tianyuan caves. Source: Sciencemag

But beyond the enormous family tree, when researchers further explored specific details about his jaw bone (or lower mandible as it is called) they found something else that was very interesting about Tianyuan man:


Title: Stable isotope dietary analysis of the Tianyuan 1 early modern human.
Authors: Hu Y, Shang H, Tong H, Nehlich O, Liu W, Zhao C, Yu J, Wang C, Trinkaus E, Richards MP.
Journal: Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):10971-4.
PMID: 19581579                     (This research article is OPEN ACCESS if you would like to read it)

In this study, the investigators analysed the carbon and nitrogen isotopes found within bone collagen samples taken from the jaw bone of Tianyuan man. In humans, the carbon and nitrogen isotope values indicate the sources of dietary protein over many years of life.

The researchers found that a substantial portion of Tianyuan man’s diet 40,000 years ago came from freshwater fish.

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

Continue reading “I’ll have the fish please” →

When SERCA goes berserker

~ Simon ~ 10 Comments

In a recent SoPD post, we discussed the importance of calcium and looked at how it interacts with the Parkinson’s-associated protein alpha synuclein, affecting the function and clustering of that protein.

During the writing of that post, another interesting research report was published on the same topic of calcium and alpha synuclein. It involved a different aspect of biology in the cell – a structure called the endoplasmic reticulum – but the findings of that study could also explain some aspects of Parkinson’s.

In today’s post, we will review the new research report, consider the biology behind the findings and how it could relate to Parkinson’s, and discuss how this new information could be used.

The original berserker. Source: Wikipedia

I can remember my father often saying “If you kids don’t be quiet, I’ll go berserk!”

Growing up, I never questioned the meaning of the word ‘berserk‘.

I simply took it as defining the state of mindless madness that my dad could potentially enter if we – his off-spring – pushed him a wee bit too far (and for the record, Dad actually ‘going berserk’ was a very rare event).

My father. But only on the odd occasion. Source: Screenrant

But now as I find myself repeating these same words to my own off-spring, I am left wondering what on Earth it actually means?

What is ‘berserk‘?

Continue reading “When SERCA goes berserker” →

On the importance of Calcium

~ Simon ~ 21 Comments

Recently researcher from the University of Cambridge reported that an imbalance in calcium and the Parkinson’s-associated protein alpha synuclein can cause the clustering of synaptic vesicles.

What does this mean? And should we reduce our calcium intake as a result?

In today’s post, we will review the research report, consider the biology behind the findings and how it could relate to Parkinson’s, and discuss what can or should be done.

Me and Brie. Source: Wikipedia

When I turned 25, I realised that my body no longer accepted cheese.

This was a very serious problem.

You see, I still really liked cheese.

A bottle of red wine, a baguette and a chunk of brie – is there any better combination in life?

So obviously my body and I had a falling out. And yes, it got ugly. I wanted things to keep going the way they had always been, so I tried to make things interesting with new and exotic kinds of cheeses, which my body didn’t want to know about it. It rejected all of my efforts. And after a while, I gradually started resenting my body for not letting me be who I was.

We sought help. We tried interventions. But sadly, nothing worked.

And then things got really bad: My body decided that it didn’t have room in its life for yogurt, milk or even ice cream anymore (not even ice cream!!!). Basically no dairy what so ever.

There’s something’s missing in my life. Source: Morellisices

OMG. How did you survive without ice cream?

Well, I’ll tell ye – it’s been rough.

All silliness aside though, here is what I know: It is actually very common to develop a lactase deficiency as we get older – lactase being the enzyme responsible for the digestion of whole milk. In fact, about 65% of the global population has a reduced ability to digest lactose after infancy (Source: NIH). I am not lactose intolerant (one of the few tests that I actually aced in my life), but I do have trouble digesting a particular component of dairy products – which can result in discomfort and socially embarrassing situations (one day over a drink I’ll tell you the ‘cheese fondue story’). Curiously, that mystery ingredient is also present in products that have no dairy (such as mayonnaise – it absolutely kills me).

But spare me your tears, if one is forced to drop a particular food group, dairy is not too bad (if I am ever forced to give up wine, I swear I’ll go postal).

My biggest concern when I dropped dairy, however, was “where was I going to get my daily requirements of calcium?“.

Understand that calcium is really rather important.

Why is calcium important?

Continue reading “On the importance of Calcium” →

Monthly Research Review – February 2018

~ Simon ~ 13 Comments

At the end of each month, the Science of Parkinson’s writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available.

In this post we review some of the research from February 2018.

The post is divided into four parts based on the type of research (Basic biology, disease mechanism, clinical research, and other news). 

Seeing shadows: Punxsutawney Phil. Source: Wordonfire

In major world event news: On the 2nd February of 2018, Punxsutawney Phil – the groundhog who resides at Gobbler’s Knob of Punxsutawney, Pennsylvania – scurried out of his little hole and saw his shadow. This omen indicates that we have a long winter. Given how hard and bitter this particular winter has been, Americans naturally rejoiced.

On the 6th February, SpaceX successfully launched a Tesla sports car into space – see the video below for the highlights (and if you don’t have time to watch it all, at the very least jump forward to 3:45 and watch the two boosters land simultaneously – surely they didn’t plan for it to be that perfect!)

In other news, on the 1st February, the Centers for Disease Control and Prevention announced that it was dramatically downsizing its epidemic prevention activities in 39 out of 49 countries, due to concerns about funding.

And of course we had the 2018 Winter Olympics – where New Zealand came in 27th on the medals board:

Source: Madison365

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

In February 2018, there were 698 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (1577 for all of 2018 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 5 pieces of PD news

Continue reading “Monthly Research Review – February 2018” →

O’mice an’ men – gang aft agley

~ Simon ~ 16 Comments

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?

Continue reading “O’mice an’ men – gang aft agley” →