Tag: Isradipine

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” →

The STEADY-PD trial results

~ Simon ~ 5 Comments

 

The results of the STEADY-PD Phase 3 clinical trial have been published. This study was evaluating the calcium channel blocker isradipine in 300 people with recently diagnosed Parkinson’s.

The results suggest that this blood pressure medication did not impact the course of the disease over the 36 months of testing (based on clinical evaluations; compared to a placebo treated group).

While this study did not reach its primary endpoint (the predetermined measure by which the treatment was assessed), a lot can be learned from this trial and it could be of interest to follow up this cohort long-term.

In today’s post, we discuss why calcium is important in Parkinson’s, explain what isradipine is, review the results of the STEADY-PD study, and explore what still could be learnt from this study.

 

Me and Brie. Source: Wikipedia

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

It had become… (how should I put this)… ‘socially embarrassing’ for me to eat cheese.

And this was a extremely serious problem.

You see, to this very day I still really like cheese.

I mean, 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 about the situation. 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 and simply refused to consider. It rejected all of my efforts. And after a while, I gradually started resenting my body for not letting me be who I felt I really was.

We sought help. We tried all kinds of interventions – I was really desperate, I couldn’t live without cheese. But sadly, nothing worked.

And then things went from bad to worse: 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.

Something’s missing in my life. Source: Morellisices

OMG. How did you survive without ice cream?!?

Continue reading “The STEADY-PD trial results” →

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?” →

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” →

The EMPRSN talk #1

~ Simon ~ 3 Comments

Recently I was invited to speak at the 6th Annual East Midlands Parkinson’s Research Support Network meeting at the Link Hotel, in Loughborough. The group is organised and run by the local Parkinson’s community and supported by Parkinson’s UK. It was a fantastic event and I was very grateful to the organisers for the invitation.

They kindly gave me two sessions (20 minutes each) which I divided into two talks: “Where we are now with Parkinson’s research?” and “Where we are going with Parkinson’s research?”. Since giving the talk, I have been asked by several attendees if I could make the slides available.

The slides from the first talk can be found by clicking here.

I have also made a video of the first talk with a commentary that I added afterwards. But be warned: my delivery of this second version of the talk is a bit dry. Apologies. It has none of my usual dynamic charm or energetic charisma. Who knew that talking into a dictaphone could leave one sounding so flat.

Anyways, here is the talk – enjoy!

I hope you find it interesting. When I have time I’ll post the second talk.

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” →