New research published in the last week provides further experimental support for numerous clinical trials currently being conducted, including one by the biotech company Sanofi Genzyme.
Researchers have demonstrated that tiny proteins which usually reside on the outer wall of cells could be playing an important role in the protein clustering (or aggregation) that characterises Parkinson’s.
In today’s post we will look at this new research and discuss what it could mean for the on going clinical trials for Parkinson’s.
The proverb ‘When the cat is away, the mice will play’ has Latin origins.
Dum felis dormit, mus gaudet et exsi litantro (or ‘When the cat falls asleep, the mouse rejoices and leaps from the hole’)
It was also used in the early fourteenth century by the French: Ou chat na rat regne (‘Where there is no cat, the rat is king’).
And then Will Shakespeare used it in Henry the Fifth(1599), Act I, Scene II:
Westmoreland, speaking with King Henry V, Gloucester, Bedford, Exeter and Warwick
“But there’s a saying very old and true,
‘If that you will France win,
Then with Scotland first begin:’
For once the eagle England being in prey,
To her unguarded nest the weasel Scot
Comes sneaking and so sucks her princely eggs,
Playing the mouse in absence of the cat,
To tear and havoc more than she can eat”
Interesting. But what does any of this have to do with Parkinson’s?
‘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.
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?
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.
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.
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.
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.
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?
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
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?
This is Lysimachos.
Pronounced: “Leasing ma horse (without the R)” – his words not mine.
He is one of the founders of an Edinburgh-based biotech company called “Parkure“.
In today’s post, we’ll have a look at what the company is doing and what it could mean for Parkinson’s disease.
The first thing I asked Dr Lysimachos Zografos when we met was: “Are you crazy?”
Understand that I did not mean the question in a negative or offensive manner. I asked it in the same way people ask if Elon Musk is crazy for starting a company with the goal of ‘colonising Mars’.
In 2014, Lysimachos left a nice job in academic research to start a small biotech firm that would use flies to screen for drugs that could be used to treat Parkinson’s disease. An interesting idea, right? But a rather incredible undertaking when you consider the enormous resources of the competition: big pharmaceutical companies. No matter which way you look at this, it has the makings of a real David versus Goliath story.
But also understand this: when I asked him that question, there was a strong element of jealousy in my voice.
Incorporated in October 2014, this University of Edinburgh spin-out company has already had an interesting story. Here at the SoPD, we have been following their activities with interest for some time, and decided to write this post to make readers aware of them.