The road ahead: Parkinson’s research in 2018

The great ice hockey player Wayne Gretzky once said “A good hockey player plays where the puck is. A great hockey player plays where the puck is going to be” (the original quote actually came from his father, Walter). 

At the start of each year, it is a useful practise to layout what is planned for the next 12 months. This can help us better anticipate where ‘the puck’ will be, and allow us to prepare for things further ahead.

2017 was an incredible year for Parkinson’s research, and there is a lot already in place to suggest that 2018 is going to be just as good (if not better).

In this post, we will lay out what we can expect over the next 12 months with regards to the Parkinson’s-related clinical trials research of new therapies.


Charlie Munger (left) and Warren Buffett. Source: Youtube

Many readers will be familiar with the name Warren Buffett.

The charming, folksy “Oracle of Omaha” is one of the wealthiest men in the world. And he is well known for his witticisms about investing, business and life in general.

Warren Buffett. Source: Quickmeme

He regularly provides great one liners like:

“We look for three things [in good business leaders]: intelligence, energy, and integrity. If they don’t have the latter, then you should hope they don’t have the first two either. If someone doesn’t have integrity, then you want them to be dumb and lazy”

“Work for an organisation of people you admire, because it will turn you on. I always worry about people who say, ‘I’m going to do this for ten years; and if I really don’t like it very much, then I’ll do something else….’ That’s a little like saving up sex for your old age. Not a very good idea”

“Choosing your heroes is very important. Associate well, marry up and hope you find someone who doesn’t mind marrying down. It was a huge help to me”

Mr Buffett is wise and a very likeable chap.

Few people, however, are familiar with his business partner, Charlie Munger. And Charlie is my favourite of the pair.

Continue reading “The road ahead: Parkinson’s research in 2018”

2017 – Year in Review: A good vintage

At the end of each year, it is a useful practise to review the triumphs (and failures) of the past 12 months. It is an exercise of putting everything into perspective. 

2017 has been an incredible year for Parkinson’s research.

And while I appreciate that statements like that will not bring much comfort to those living with the condition, it is still important to consider and appreciate what has been achieved over the last 12 months.

In this post, we will try to provide a summary of the Parkinson’s-related research that has taken place in 2017 (Be warned: this is a VERY long post!)


The number of research reports and clinical trial studies per year since 1817

As everyone in the Parkinson’s community is aware, in 2017 we were observing the 200th anniversary of the first description of the condition by James Parkinson (1817). But what a lot of people fail to appreciate is how little research was actually done on the condition during the first 180 years of that period.

The graphs above highlight the number of Parkinson’s-related research reports published (top graph) and the number of clinical study reports published (bottom graph) during each of the last 200 years (according to the online research search engine Pubmed – as determined by searching for the term “Parkinson’s“).

PLEASE NOTE, however, that of the approximately 97,000 “Parkinson’s“-related research reports published during the last 200 years, just under 74,000 of them have been published in the last 20 years.

That means that 3/4 of all the published research on Parkinson’s has been conducted in just the last 2 decades.

And a huge chunk of that (almost 10% – 7321 publications) has been done in 2017 only.

So what happened in 2017? Continue reading “2017 – Year in Review: A good vintage”

Multiple System Atrophy: A prion disease?

‘Parkinsonisms’ refer to a group of neurological conditions that cause movement features similar to those observed in Parkinson’s disease. They include multiple system atrophy (MSA) and Progressive supranuclear palsy (PSP) and idiopathic Parkinson’s.

Newly published research now shines a light on a possible mechanism for differentiating between multiple system atrophy and idiopathic Parkinson’s.

In today’s post we will look at what multiple system atrophy is, review the new research report, and discuss what these results could mean for the Parkinson’s community.


Brain immaging of multiple system atrophy–related spatial covariance pattern (MSARP) and Parkinson disease–related spatial covariance pattern (PDRP). Source: Neurology

For a long time I have been looking to write a piece of Multiple system atrophy.

I have been contacted by several readers asking for more information about it, and the only thing really delaying me – other than the tsunami of Parkinson’s related research that I am currently trying to write posts for – was the lack of a really interesting piece of research to base the post around.

Guess what came into my inbox yesterday:

Title: Familial Parkinson’s point mutation abolishes multiple system atrophy prion replication.
Authors: Woerman AL, Kazmi SA, Patel S, Aoyagi A, Oehler A, Widjaja K, Mordes DA, Olson SH, Prusiner SB.
Journal: Proc Natl Acad Sci U S A. 2017 Dec 26. pii: 201719369.
PMID: 29279394

This is a really interesting piece of research, that continues a line of other really interesting research.

And if it is independently replicated and verified, it will have massive implications for the Parkinson’s community, particularly those affected by Multiple System Atrophy.

But before we deal with that, let’s start with the obvious question:

What is Multiple System Atrophy?

Continue reading “Multiple System Atrophy: A prion disease?”

Novartis focuses on improving PARKIN control

Last week, as everyone was preparing for Christmas celebrations, researchers at the pharmaceutic company Novartis published new research on a gene that is involved with Parkinson’s, called PARKIN (or PARK2).

They used a new gene editing technology – called CRISPR – to conduct a large screening study to identify proteins that are involved with the activation of PARKIN.

In today’s post we will look at what PARKIN does, review the research report, and discuss how these results could be very beneficial for the Parkinson’s community.


Source: Novartis

As many people within the Parkinson’s community will be aware, 2017 represented the 200th anniversary of the first report of Parkinson’s disease by James Parkinson.

It also the 20th anniversary of the discovery of first genetic mutation (or variant) that increases the risk of developing Parkinson’s. That genetic variation occurs in a region of DNA (a gene) called ‘alpha synuclein’. Yes, that same alpha synuclein that seems to play such a critical role in Parkinson’s (Click here to read more about the 20th anniversary).

In 2018, we will be observing the 20th anniversary of the second genetic variation associated with Parkinson.

That gene is called PARKIN:

Title: Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
Authors: Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N
Journal: Nature. 1998 Apr 9; 392(6676):605-8
PMID: 9560156

In 1998, Japanese researchers published this report based on 5 individuals from 4 Japanese families who were affected by juvenile-onset Parkinson’s. In family 1, the affected individual was a female, 43 years old, born of first-cousin parents, and her two younger brothers are healthy. Her condition was diagnosed in her teens and it had then progressed very slowly afterwards. Her response to L-dopa was very positive, but L-dopa-induced dyskinesia were frequent. In family 2-4, affected individuals (born to unrelated parents) exhibited very similar clinical features to the subject in family 1. The age of onset was between 18 to 27 years of age.

Using previous research and various techniques the investigators were able to isolate genetic variations that were shared between the 5 affected individuals. They ultimately narrowed down their search to a section of DNA containing 2,960 base pairs, which encoded a protein of 465 amino acids.

They decided to call that protein PARKIN.

PARKIN Protein. Source: Wikipedia

How much of Parkinson’s is genetic?

Continue reading “Novartis focuses on improving PARKIN control”

Inhibiting LRRK2: The Denali Phase I results

Denali

This week Denali Therapeutics released the results of a phase I clinical trial of their primary product, called DNL-201.

DNL-201 is a LRRK2 inhibitor that the company is attempting to take to the clinic for Parkinson’s disease. 

In today’s post we will look at what LRRK2 is, how an inhibitor might help in Parkinson’s, and what the results of the trial actually mean.


Wonder_Lake_and_Denali

Denali. Source: Wikipedia

Denali (Koyukon for “the high one”; also known as Mount McKinley) in Alaska is the highest mountain peak in North America, with a summit elevation of 20,310 feet (6,190 m) above sea level. The first verified ascent to Denali’s summit occurred on June 7, 1913, by four climbers Hudson Stuck, Harry Karstens, Walter Harper, and Robert Tatum.

Tatum (left), Karstens (middle), and Harper (right). Source: Gutenberg

Robert Tatum later commented, “The view from the top of Mount McKinley is like looking out the windows of Heaven!”

More recently another adventurous group associated with ‘Denali’ have been trying to scale lofty heights, but of a completely different sort from the mountaineering kind.

Continue reading “Inhibiting LRRK2: The Denali Phase I results”

James: His legacy (Part 4)

On Tuesday 21st December, 1824, James Parkinson passed away in his home – two days after suffering a stroke.

It was the end of an amazing and extremely productive life.

In this post about James Parkinson – the final in the series of four observing the 200th anniversary of his first observation of Parkinson’s disease – we look at what happened following his death, and reflect on his overall legacy.


St Leonard’s church in Hoxton, London – James’ church

At the end of the third post on the life of James Parkinson (Click here to read that post), the Battle of Waterloo had just occurred and James was publishing the last of his writings.

One of the last major events in the life of James Parkinson occurred in 1823, when James was awarded the Royal College of Surgeons’ first Gold Medal.

Understand that this was a big deal.

The college had established the award way back in 1802 for “distinguished labours, researches and discoveries”. But it took them a full 21 years to find anyone that they thought worthy enough to be the first recipient.

And that first recipient: one James Parkinson

This event, however, represents very nicely how the legacy of James has changed over time. While the world currently associates James Parkinson with a neurological condition that he first described in 1817, the Royal College of Surgeons awarded him their first gold medal not for any of his medical publications, but rather for his “splendid Work on Organic Remains”.

parkinson3

Source: Lindahall

As I have written before, James was a bit of a rockstar to the geological/palaeontology community. His writings on what he called his “favourite science”, had earned him an international reputation and one has to wonder how he would feel now if he knew that his reputation lies elsewhere.

As JP aficionado Dr Cherry Lewis once wrote: history is fickle.

Continue reading “James: His legacy (Part 4)”

A virtual reality for Parkinson’s: Keapstone

parkinsons_virtual_biotech_graphic

In 2017, Parkinson’s UK – the largest charitable funder of Parkinson’s disease research in Europe – took a bold step forward in their efforts to find novel therapies.

In addition to funding a wide range of small and large academic research projects and supporting clinical trials, they have also decided to set up ‘virtual biotech’ companies – providing focused efforts to develop new drugs for Parkinson’s, targeting very specific therapeutic areas.

In today’s post we will look at the science behind their first virtual biotech company: Keapstone.


Virtual_Reality_Oculus_Rift

A virtual world of bioscience. Source: Cast-Pharma

I have previously discussed the fantastic Parkinson’s-related research being conducted at Sheffield University (Click here to read that post). Particularly at the Sheffield Institute for Translational Neuroscience (SITraN) which was opened in 2010 by Her Majesty The Queen. It is the first European Institute purpose-built and dedicated to basic and clinical research into Motor Neuron Disease as well as other neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease.

The research being conducted at the SITraN has given rise to multiple lines of research following up interesting drug candidates which are gradually being taken to the clinic for various conditions, including Parkinson’s.

It’s all very impressive.

And apparently I’m not the only one who thought it was impressive.

Continue reading “A virtual reality for Parkinson’s: Keapstone”

PAQ-ing more punch for Parkinson’s

Punch

In the 1990, scientists identified some fruits that they suspected could give people Parkinson’s. 

These fruit are bad, they reported.

More recently, researchers have identified chemicals in that exist in those same fruits that could potential be used to treat Parkinson’s. 

These fruit are good, they announce.

In today’s post, we will explain why you should avoid eating certain members of the Annonaceae plant family and we will also look at the stream of research those plants have given rise to which could provide a novel therapy for Parkinson’s.


les_saintes_guadeloupe-1

Guadeloupe. Source: Bluefoottravel

In the late 1990s, researchers noticed something really odd in the French West Indies.

It had a very strange distribution of Parkinsonisms.

What are Parkinsonisms?

‘Parkinsonisms’ refer to a group of neurological conditions that cause movement features similar to those observed in Parkinson’s disease, such as tremors, slow movement and stiffness. The name ‘Parkinsonisms’ is often used as an umbrella term that covers Parkinson’s disease and all of the other ‘Parkinsonisms’.

Parkinsonisms are generally divided into three groups:

  1. Classical idiopathic Parkinson’s disease (the spontaneous form of the condition)
  2. Atypical Parkinson’s (such as multiple system atrophy (MSA) and Progressive supranuclear palsy (PSP))
  3. Secondary Parkinson’s (which can be brought on by mini strokes (aka Vascular Parkinson’s), drugs, head trauma, etc)

Source: Parkinsonspt

Some forms of Parkinsonisms that at associated with genetic risk factors, such as juvenile onset Parkinson’s, are considered atypical. But as our understanding of the genetics risk factors increases, we may find that an increasing number of idiopathic Parkinson’s cases have an underlying genetic component (especially where there is a long family history of the condition) which could alter the structure of our list of Parkinsonisms.

So what was happening in the French West Indies?

Continue reading “PAQ-ing more punch for Parkinson’s”

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 “The anti-depressing research of antidepressants”

The TAU of Parkinson’s

Here at the SoPD, we regularly talk about the ‘bad boy’ of Parkinson’s disease – a protein called Alpha Synuclein.

Twenty years ago this year, genetic variations were identified in the alpha synuclein gene that increase one’s risk of developing Parkinson’s. In addition, alpha synuclein protein was found to be present in the Lewy bodies that are found in the brains of people with Parkinson’s. Subsequently, alpha synuclein has been widely considered to be the villain in this neurodegenerative condition and it has received a lot of attention from the Parkinson’s research community.

But it is not the only protein that may be playing a role in Parkinson’s.

Today’s post is all about TAU.


Source: Wallpaperswide

I recently informed my wife that I was thinking of converting to Taoism.

She met this declaration with more of a smile than a look of shock. And I was expecting the latter, as shifting from apatheism to any form of religious belief is a bit of a leap you will appreciate.

When asked to explain myself, I suggested to her that I wanted to explore the mindfulness of what was being proposed by Lao Tzu (the supposed author of the Tao Te Ching – the founding document of Taoism).

This answer also drew a smile from her (no doubt she was thinking that Simon has done a bit of homework to make himself sound like he knows what he was talking about).

But I am genuinely curious about Taoism.

Most religions teach a philosophy and dogma which in effect defines a person. Taoism – which dates from the 4th century BCE – flips this concept on its head. It starts by teaching a single idea: The Tao (or “the way”) is indefinable. And then it follows up by suggesting that each person should discover the Tao on their own terms. Given that most people would prefer more concrete definitions in their own lives, I can appreciate that a lot of folks won’t go in for this approach.

Personally speaking, I quite like the idea that the Tao is the only principle and everything else is a just manifestation of it.

According to Taoism, salvation comes from just one source: Following the Tao.

Source: Wikipedia

Oh and don’t worry, I’m not going to force any more philosophical mumbo jumbo on you – Taoism is just an idea I am exploring as part of a terribly clichéd middle-life crisis I’m working my way through (my wife’s actual response to all of this was “why can’t you just be normal and go buy a motor bike or something?”).

My reason for sharing this, however, is that this introduction provides a convenient segway to what we are actually going to talk about in this post.

You see, some Parkinson’s researchers are thinking that salvation from neurodegenerative conditions like Parkinson’s will come from just one source: Following the TAU.

What is TAU?

Continue reading “The TAU of Parkinson’s”