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 March 2018.
The post is divided into four parts based on the type of research (Basic biology, disease mechanism, clinical research, and other news).
So, what happened during March 2018?
In world news:
March 25th – Qantas launches direct non-stop Boeing 787 Dreamliner flights between Perth Airport and Heathrow Airport, making it the first commercially non-stop service between Australia and the United Kingdom (17 hours on a plane – strewth!).
Boeing 787 Dreamliner. Source: Deredactie
March 14th – Prof Stephen Hawking, English theoretical physicist and cosmologist, sadly passed away at age 76. Diagnosed with in a very rare early-onset, slow-progressing form of Amyotrophic lateral sclerosis (ALS; also known as motor neurone disease or MND) in 1963 at age 21, he was gradually left him wheel chair bound. An amazing mind and a sad loss.
Prof Stephen Hawking. Source: BBC
A funeral for Prof Hawking was held in Cambridge. The bell at Great St. Mary’s tolled 76 times at the start of the service. His remains will be cremated and his ashes will be interred at London’s Westminster Abbey near the remains of Isaac Newton.
King’s Parade in Cambridge was absolutely packed with mourners. Source: News.rthk
March 19th – In other sad news, ‘Sudan’, the world’s last male northern white rhinoceros died in Kenya, making the subspecies ‘functionally extinct’. Poachers had reduced the population from 2000 in the 1960s to just 15 1980s, and efforts to keep the species alive .
Sudan, the last surviving male northern white rhino. Source: PBS
March 24 – In over 800 cities internationally, people participated in student-led demonstrations against gun violence and mass shootings, calling for stronger gun control in the ‘March for our lives‘.
And finally, on the 17th March, a driver in Milton Keynes (UK) got into big trouble with the law when he was pulled over and presented a police officer with an obvious fake drivers license (Source: Sky News):
Fake news Mr Trump? Clearly a fake. Everyone knows Homer lives at 742 Evergreen Terrace!
In the world of Parkinson’s research, a great deal of new research and news was reported:
This is one of those post (read: rants) where I want to put an idea out into the ether for someone to chew on. It starts with a very simple question:
Why is ‘the drug’ the focus of a clinical trial?
If our goal is to find beneficial therapies for people with Parkinson’s, then the way we currently clinically test drugs is utterly nonsensical.
And if we do not change our “we’ve always done it this way” mindset, then we are simply going to repeat the mistakes of the past. Others are changing, so why aren’t we?
In today’s post, we will consider one possible alternative approach.
Why is ‘the drug‘ the focus of a clinical trial?
The way we clinically test drugs makes absolutely no sense when you actually stop and think about it.
Other medical disciplines (such as oncology) have woken up to this fact, and it is time for the field of Parkinson’s research to do this same.
Let me explain:
On this website, we regularly talk about a Parkinson’s-associated protein called Alpha Synuclein.
It is widely considered to be ‘public enemy #1’ in the world of Parkinson’s research, or at the very least one of the major ‘trouble makers’. It is a curious little protein – one of the most abundant proteins in your brain.
But did you know that there are different ‘species’ of alpha synuclein?
And recently researchers in Florida announced that they had identified an all new species of alpha synuclein that they have called “P-alpha-syn-star” or Pα-syn*.
In today’s post, we will discuss what is meant by the word ‘species’, look at the different species of alpha synuclein, and explore what this new species could mean for the Parkinson’s community.
This microscopic creature is called Macrobiotus shonaicus.
Isn’t it cute?
The researchers that discovered it found it in a Japanese parking lot.
It is one of the newest species of life discovered to date (Click here for the research report). It is a species of Tardigrade (meaning “slow stepper”; also known as a water bear or moss piglet). And for the uninitiated: Tardigrade are remarkable creatures.
Tardigrade. Source: BBC
They measure just 0.5 mm (0.02 in) long, there are approximately 1,150 known species of them, and they have been around for a VERY long time – with fossil records dating back to the Cambrian period (500 million years ago).
The tree of life (try and find the dinosaurs). Source: Evogeneao
But most importantly, tardigrade are EXTREMELY resilient:
- they are the first known animals to survive in hard vacuum and UV radiation of outer space. Some of them can withstand extreme cold – down to temperatures of −458 °F (−272 °C), while other species of Tardigrade can withstand extremely hot temperatures – up to 300 °F (150 °C) (Click here to read more)
- they can withstand 1,000 times more radiation than other animals (Click here for more on that)
- some species of Tardigrade can also withstand pressure of 6,000 atmospheres (that is nearly SIX times the pressure of water in the deepest ocean trench – the Mariana trench! Click here for more on this)
- They are one of the few groups of species that are capable of suspending their metabolism; surviving for more than 30 years at −20 °C (−4 °F – Click here to read about this)
They are utterly remarkable creatures.
Great, but what does this have to do with Parkinson’s? Continue reading
In an effort to better understand Parkinson’s, researchers have repeatedly analysed data from large epidemiological studies in order to gain insight into factors that could have a possible causal influence in the development of the condition.
This week a manuscript was made available on the preprint website BioRxiv that provided us with a large database of information about aspects of life that are associated with increased incidence of Parkinson’s.
Some new associations have been made… and some of them are intriguing, while others are simply baffling!
In today’s post, we will have a look at what has been learnt from epidemiological research on Parkinson’s, and then discuss the new research and what it could mean for Parkinson’s.
What are the differentiators? Source: Umweltbundesamt
What makes me different from you?
Other than my ridiculous height and the freakishly good looks, that is. What influential factors have resulted in the two of us being so different?
Yes, there is the genetics component playing a role, sure. 7,500 generations of homo sapien has resulted in a fair bit of genetic variation across the species (think red hair vs brown hair, dark skin vs light skin, tall Scandinavians vs African pygmies, etc). And then there are aspects like developmental noise and epigenetics (factors that cause modifications in gene activity rather than altering the genetic code itself).
And over-riding all of this, is a bunch of other stuff that we generally refer to simply as ‘life’. Habits and routines, likes and dislikes, war and famine, etc. The products of how we interact with the environment, and how it interacts with us.
But which of all these factors plays a role in determining our ultimate outcome?
It is a fascinating question. One that absorbs a large area of medical research, particularly with regards to factors that could be influential in causing a specific chronic conditions.
What does this have to do with Parkinson’s?
As we have previously discussed, 2017 was a fantastic year for Parkinson’s research (Click here to read that post). And as we approach the end of January, it is already apparent that 2018 is likely to be as good if not better (Click here for an overview of what to expect from 2018).
The transition into a new year brings with it a period of reflection and resolutions. At the start of each year I usually have a post that asks for readers feedback regarding how the SoPD website could be improved.
This year is going to be slightly different.
In today’s post we will discuss some of the ideas that I have in mind for 2018 – any and all reader feedback would be greatly appreciated.
The title of today’s post is a play on words. It is a salute to the song ‘My generation’ by the rock band “The Who” (click on the image above to hear the song). The song was released as a single on the 29th October 1965. It reached No. 2 in the UK and No. 74 in America.
Despite never actually reaching No.1, Rolling Stone magazine still named ‘My generation’ the 11th greatest song of all time (Source). The British music magazine New Musical Express (NME), noted that the song “encapsulated the angst of being a teenager,” and was a “nod to the mod counterculture” (Source).
Pete Townshend. Source: Rnrchemist
The Who‘s guitarist, Pete Townshend, apparently wrote “My Generation,” on his 20th birthday (19th May 19th, 1965), while riding a train from London to Southampton for a television appearance. He claims that it was never meant to be the battle cry for young mod rebels that it went on to become.
Rather it was intended to express Townshend’s fears about ‘the impending strictures of adult life’. He preferred to stay young, free and experimental.
I am not having any teenage angst issues or fearing the very current strictures of adult life. I am simply using a play of the song’s title here in order to discuss a new year’s resolution I have made regarding the SoPD website over the never 12 months.
Let me explain.
As the age of personalised medicine approaches, innovative researchers are rethinking the way we conduct clinical studies. “Rethinking” in radical ways – think: individualised clinical trials!
One obvious question is: Can you really conduct a clinical trial involving just one participant?
In this post, we will look at some of the ideas and evaluate the strengths and weaknesses these approaches.
A Nobel prize medal. Source: Motley
In the annals of Nobel prize history, there are a couple winners that stands out for their shear….um, well,…audacity.
One example in particular, was the award given to physician Dr Werner Forssmann. In 1956, Andre Cournand, Dickinson Richards and Forssmann were awarded the Nobel Prize in Physiology or Medicine “for their discoveries concerning heart catheterisation and pathological changes in the circulatory system”. Forssmann was responsible for the first part (heart catheterisation).
In 1929, at the age of 25, Forssmann performed the first human cardiac catheterisation – that is a procedure that involves inserting a thin, flexible tube directly into the heart via an artery (usually in the arm, leg or neck). It is a very common procedure performed on a daily basis in any hospital today. But in 1929, it was revolutionary. And the audacious aspect of this feat was that Forssmann performed the procedure on himself!
And if you think that is too crazy to be true, please read on.
But be warned: this particular story gets really bonkers.
We have previously discussed the powerful antioxidant Resveratrol, and reviewed the research suggesting that it could be beneficial in the context of Parkinson’s disease (Click here to read that post).
I have subsequently been asked by several readers to provide a critique of the Parkinson’s-associated research focused on Resveratrol’s twin sister, Pterostilbene (pronounced ‘Terra-still-bean’).
But quite frankly, I can’t.
Why? Because there is NO peer-reviewed scientific research on Pterostilbene in models of Parkinson’s disease.
In today’s post we will look at what Pterostilbene is, what is known about it, and why we should seriously consider doing some research on this compound (and its cousin Piceatannol) in the context of Parkinson’s disease.
Blue berries are the best natural source of Pterostilbene. Source: Pennington
So this is likely to be the shortest post in SoPD history.
Because there is nothing to talk about.
There is simply no Parkinson’s-related research on the topic of today’s post: Pterostilbene. And that is actually a crying shame, because it is a very interesting compound.
What is Pterostilbene?
Like Resveratrol, Pterostilbene is a stilbenoid.
Stilbenoids are a large class of compounds that share the basic chemical structure of C6-C2-C6:
Resveratrol is a good example of a stilbenoid. Source: Wikipedia
Stilbenoids are phytoalexins (think: plant antibiotics) produced naturally by numerous plants. They are small compounds that become active when the plant is under attack by pathogens, such as bacteria or fungi. Thus, their function is generally considered to part of an anti-microbial/anti-bacterial plant defence system for plants.
The most well-known stilbenoid is resveratrol which grabbed the attention of the research community in a 1997 study when it was found to inhibit tumour growth in particular animal models of cancer:
The protein Alpha Synuclein has long been considered the bad-boy of Parkinson’s disease research. Possibly one of the main villains in the whole scheme of things.
New research suggests that it may be interfering with a neuroprotective pathway, leaving the affected cell more vulnerable to stress/toxins. But that same research has highlighted a novel beneficial feature of an old class of drugs: MAO-B inhibitors.
In today’s post we will outline the new research, discuss the results, and look at whether this new Trk warrants a re-think of MAO-B inhibitors.
The great Harry Houdini. Source: Wikipedia
I’m not sure about you, but I enjoy a good magic trick.
That exhilarating moment when you are left wondering just one thing: How do they do that?
(Seriously, at 4:40 a baguette comes out of thin air – how did he do that?)
Widely believed to have been one of the greatest magicians of all time (Source), Harry Houdini is still to this day revered among those who practise the ‘dark arts’.
Born Erik Weisz in Budapest (in 1874), Houdini arrived in the US in 1878. Fascinated with magic, in 1894, he launched his career as a professional magician and drew attention for his daring feats of escape. He renamed himself “Harry Houdini” – the first name being derived from his childhood nickname, “Ehrie,” and the last name paying homage to the great French magician Jean Eugène Robert-Houdin. In 1899, Houdini’s act caught the eye of Martin Beck, an entertainment manager, and from there the rest is history. Constantly upping the ante, his feats became bolder and more death defying.
And the crowds loved him.
From stage, he moved on to film – ultimately starting his own production company, Houdini Picture Corporation. In addition, he was a passionate debunker of psychics and mediums, his training in magic helping him to expose frauds (which turned him against his former friend Sir Arthur Conan Doyle, who believed deeply in spiritualism).
This is all very interesting, but what does any of it have to do with Parkinson’s?
In addition to looking at current Parkinson’s disease research on this website, I like to look at where technological advances are taking us with regards to future therapies.
In July of this year, I wrote about a new class of engineered viruses that could potentially allow us to treat conditions like Parkinson’s disease using a non-invasive, gene therapy approach (Click here to read that post). At the time I considered this technology way off at some point in the distant future. Blue sky research. “Let’s wait and see” – sort of thing.
So imagine my surprise when an Italian research group last weekend published a new research report in which they used this futurist technology to correct a mouse model of Parkinson’s disease. Suddenly the distant future is feeling not so ‘distant’.
In today’s post we will review and discuss the results, and look at what happens next.
Technological progress – looking inside the brain. Source: Digitial Trends
I have said several times in the past that the pace of Parkinson’s disease research at the moment is overwhelming.
So much is happening so quickly that it is quite simply difficult to keep up. Not just here on the blog, but also with regards to the ever increasing number of research articles in the “need to read” pile on my desk. It’s mad. It’s crazy. Just as I manage to digest something new from one area of research, two or three other publications pop up in different areas.
But it is the shear speed with which things are moving now in the field of Parkinson’s research that is really mind boggling!
Take for example the case of Squalamine.
In February of this year, researchers published an article outlining how a drug derived from the spiny dogfish could completely suppress the toxic effect of the Parkinson’s associated protein Alpha Synuclein (Click here to read that post).
The humble dogfish. Source: Discovery
And then in May (JUST 3 MONTHS LATER!!!), a biotech company called Enterin Inc. announced that they had just enrolled their first patient in the RASMET study: a Phase 1/2a randomised, controlled, multi-center clinical study evaluating a synthetic version of squalamine (called MSI-1436) in people with Parkinson’s disease. The study will enrol 50 patients over a 9-to-12-month period (Click here for the press release).
Wow! That is fast.
Yeah, I thought so too, but then this last weekend a group in Italy published new research that completely changed my ideas on the meaning of the word ‘fast’. Regular readers will recall that in July I discussed amazing new technology that may one day allow us to inject a virus into a person’s arm and then that virus will make it’s way up to the brain and only infect the cells that we want to have a treatment delivered to. This represents non-invasive (as no surgery is required), gene therapy (correcting a medical condition with the delivery of DNA rather than medication). This new study used the same virus we discussed in July.
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?