Recently some researchers conducted an analysis of some postmortem brains from people with Parkinson’s and they discovered something rather curious.
Half of the brains that they analysed came from people with Parkinson’s who had been given deep brain stimulation (or DBS) to help manage their symptoms. When the researchers analysed the mitochondria – the powerstations of each cell – in the dopamine neurons of these brain, they found that the DBS treatment had helped to improve the number of mitochondria in these cells.
Specifically, the DBS treatment “seemed to have inhibited or reversed the reduction in mitochondrial volume and numbers” that was observed in the Parkinson’s brains that had not had DBS.
In today’s post, we will look at what DBS is, what the new research report found, and what these new findings could mean for the Parkinson’s community.
The worst thing. Source: Greatist
Do you know the worst thing that happens to us in life?
We wake up each day.
Every day of our lives (so far) we have woken up and been given – without any kind of justification – another 16 or so hours to do whatever we want with.
Regardless of one’s physical/mental state, this is a bad thing.
This continuous pattern is what is referred to in psychology as a ‘continuous schedule of reinforcement’. Such regimes instill complacency and – worse – expectation. They quickly lead to people taking things for granted. All of us are guilty of thinking “I’ll do it tomorrow”.
Such a continuous pattern of reinforcement does not prepare one well for a life in scientific research, where there isn’t a constant schedule of reinforcement (quite the opposite actually). Experiments regularly go wrong (reagents/equipment fail), grants/manuscripts get rejected – it can be rather brutal.
But here is where the addictive component of science comes into effect. Every so often, something works. And even better, every so often something unexpected happens – an ‘intermittent/irregular schedule of reinforcement’. An experiment will occasionally spit out a completely unexpected result, which could change everything.
These are the moments of insights that researchers are slaving for. The instant that they are the first to “walk on the moon”.
They are moments to savour.
And this must have been the state of mind for some researchers who dicovered something surprising and absolutely remarkable recently while they were looking at some postmortem brains from individuals with Parkinson’s who had been treated with deep brain stimulation.
What is deep brain stimulation?
Approximately 1 person with Parkinson’s in every 100 will have a genetic variation in a specific section of their DNA that is referred to as LRRK2 – pronounced ‘lark 2’. The variation results in changes to the activity of the LRRK2 protein, and these changes are suspected of influencing the course of LRRK2-associated Parkinson’s.
Numerous biotech companies are now developing LRRK2 targetting agents that will modulate the activity of the LRRK2 protein.
Recently, however, a research report was published which points towards a potentially accessible method of LRRK2 modulation – one of the active forms of vitamin B12 – and if this research can be independently replicated, it may provide certain members of the Parkinson’s community with another means of dealing with the condition.
In today’s post, we will look at what LRRK2 is, review the new research, and discuss what could happen next.
This is Sergey Brin.
You may have heard of him – he was one of the founders of a small company called “Google”. Apparently it does something internet related.
Having made his fortune changing the way we find stuff, he is now turning his attention to other projects.
One of those other projects is close to our hearts: Parkinson’s.
Why is he interested in Parkinson’s?
In 1996, Sergey’s mother started experiencing numbness in her hands. Initially it was believed to be a bit of RSI (Repetitive strain injury). But then her left leg started to drag. In 1999, following a series of tests and clinical assessments, Sergey’s mother was diagnosed with Parkinson’s.
The Brin Family – Sergey and his mother on the right. Source: CS
It was not the first time the family had been affected by the condition – Sergey’s late aunt had also had Parkinson’s.
Given this coincidental family history of this particular condition, both Sergey and his mother decided to have their DNA scanned for any genetic errors (also called ‘variants’ or ‘mutations’) that are associated with an increased risk of developing Parkinson’s. And they discovered that they were both carrying a genetic variation in a gene (a section of DNA that provides the instructions for making a protein) called PARK8 – one of the Parkinson’s-associated genes (Click here to read more about the genetics of Parkinson’s and the PARK genes).
The PARK8 gene is also known as Leucine-rich repeat kinase 2 (or LRRK2 – pronounced ‘lark 2’).
What is LRRK2?
Today saw the publication of one of my favourite stories of Parkinson’s research.
It is a tale of courage, serendipity, hard work, and (most importantly) an idea for a research project that came from the Parkinson’s community, but has now opened new doors for researchers and could have important implications for everyone.
In 2012, former nurse Joy Milne was attending a Parkinson’s support group meeting in Edinburgh (Scotland) when she bravely asked the scientist presenting research that day, “Do people with Parkinson’s smell different?”
What happened next is likely to become that stuff of legend.
In today’s post, we will discuss the back story, review a new research report investigating the smell of Parkinson’s, and consider what the results could mean for the Parkinson’s community.
Erasto Mpemba & Denis Osborne. Source: Rekordata
In 1963, Dr. Denis G. Osborne – from the University College in Dar es Salaam – was invited to give a lecture on physics to the students at Magamba Secondary School (Tanganyika, Tanzania). At the end of his lecture, a 13 year old student, named Erasto Mpemba, stood up and asked Dr Osbrone:
“If you take two similar containers with equal volumes of water, one at 35 °C (95 °F) and the other at 100 °C (212 °F), and put them into a freezer, the one that started at 100 °C (212 °F) freezes first. Why?”
The question was met by ridicule from his fellow classmates.
But to his credit, Dr Osborne went back to his lab and conducted some experiments based on the question, confirming Mpemba’s observation. Together they published the results in 1969, and the phenomenon (the process in which hot water can freeze faster than cold water) is now referred to as the Mpemba effect.
Mpemba effect. Source: Wikipedia
The point is: All scientific discoveries start with an observation, followed by an experiment.
And scientists do not have a monopoly on this.
There have been many cases of ‘laypeople’ – like Erasto Mpemba – making important observations. And recently the Parkinson’s world had a perfect example of this. It’s very own Erasto Mpemba moment.
What are you talking about?
Recently a really interesting research report was published that presented several rather amazing findings.
The researchers forced dopamine-producing cells in a rodent brain to start making a protein called neuromelanin and by doing this, they witnessed the occurence of Parkinson’s-like features (motor issues, Lewy body-like structures, and cell death).
The report also suggested a method by which this outcome could be reduced or rescued.
But the amazing part is that neuromelanin was previously considered to be protective and this new finding suggests we may need to rethink that idea.
In today’s post, we will discuss what neuromelanin is, what this new report found, and how this new knowledge could be useful in the context of Parkinson’s.
Prof Heiko Braak. Source – Memim.com
This is Prof Heiko Braak.
Many years ago, he sat down and examined hundreds of postmortem brains from people with Parkinson’s.
He had collected brains from people who passed away at different stages of the condition, and was looking for any kind of pattern that might explain where and how the disease starts. His research led to what is referred to as the “Braak staging” model of Parkinson’s – a six step explanation of how the condition spreads up from the brain stem (the top of the spinal cord) and into the rest of the brain (Click here and here to read more about this).
The Braak stages of PD. Source: Nature
Braak found that certain populations of cells in the brain were more vulnerable to Parkinson’s than others, such as the dopamine neurons in a region called the substantia nigra, the noradrenergic neurons of the locus coeruleus, and the neurons of the dorsal motor nucleus of the vagus (don’t worry about what any of those names actually mean, I’m just trying to sound smart and make you think that I know what I’m taking about).
One feature that all of these populations of neurons all share in common – in addition to vulnerability to Parkinson’s – is the production of pigment called neuromelanin.
What is neuromelanin?
Approximately 40% of the people affected by Parkinson’s are female. This number can vary across regions, but women still make up a large portion of the affected community.
That said, there is unfortunately very little research investigating women’s issues in Parkinson’s.
There are now efforts to correct this situation, however, and this change is being brought about by members of the affected community.
In today’s post, we will discuss some of what is known about how Parkinson’s affects women differently.
Why is today – the 8th March – called International women’s day? (backdated due to @#%$£&* technical issues!).
I don’t actually know. Perhaps because it’s politically correct that everyone should get their own day/month now?
The United Nations began celebrating International Women’s Day on the 8th March in 1975. But observation of the day date back to the early years of that century, and although the suffrage movement was occurring at the same time, International women’s day was very much a socialist idea.
And this shows itself in the timeline of events. For example, International Women’s Day was first observed on the 19th March, 1911 in Germany thanks to socialist activists like Luise Zietz, Käte Duncker and Clara Zetkin. But it wasn’t until 1918 that women were actually given the right to vote.
And remarkably, it was not until 1977 that the United Nations General Assembly invited its member states to proclaim the 8th March as the “UN Day for women’s rights and world peace”.
Interesting. But what does this have to do with Parkinson’s?
There is an imbalance in the amount of research being conducted on women in Parkinson’s.
In particular, there is a poverty of information regarding aspects of daily life for women living with Parkinson’s, especially those with young onset Parkinson’s.
What do you mean?
If you go to the medical research search engine Pubmed, and type in Parkinson’s and menopause, there are only 107 publications (dating back to 1971, 41 of them since 2010). To put that in context, there are over 105,000 research reports on Parkinson’s on the pubmed database. And most of them are not about menopause research, they simply mention the word menopause in their text. Similarly there are only 25 reports on parkinson’s and menstruation (and only 6 of them have been conducted since 2000!?!?).
Searching for male associated key words such as parkinson’s and prostate yeilds 177 publications (104 of which have been published since 2010 only).
And searching for Parkinson’s and male results in 43,000 reports, but searching for Parkinson’s and female only gives 36,000 reports.
So why the disparity?
“The measure of who we are is what we do with what we have” – Vince Lombardi
The measuring of Parkinson’s is complicated. There is such enormous variability between individual cases that the task of assessing people is very difficult.
The primary method that is used in clinics around the world is the Unified Parkinson’s Disease Rating Scale (or UPDRS). It is by no means perfect, and recently (in the wake of several unsuccessful clinical trials) there has been heated debate as to whether it is really up to the task.
Does it accurately reflect the condition? Does it really capture the lived experience? Can it pick up subtle changes associated with potentially disease modifying therapies in clinical trials? Or is it simply a “we’ve always done it this way” kind of tool?
In today’s post, we will look at what the UPDRS is, discuss some of the criticisms associated with it, and consider what solutions to those issues could look like.
This is Andy Grove and his story is rather remarkable.
Born in 1936 to a Jewish family in Budapest, he managed to survive the Nazis, and then fleed Hungary when Soviet tanks started rolling in. Arriving in the US with absolutely nothing, he taught himself English, before going to City College of New York and later the University of California (Berkeley) where he received a PhD in chemical engineering.
And that was just the start of his amazing tale.
After completing his PhD (and publishing a textbook on semiconductors), Grove joined the seminal Silicon Valley company – Fairchild Semiconductor – in 1963. He worked his way up from researcher to assistant director of development, before becoming the first person that Robert Noyce and Gordon Moore (of Moore’s Law fame) hired after they departed Fairchild to start their own little company in 1968.
The name of that company was Intel.
Grove also worked his way up the ladder at Intel – from director of engineering to CEO – and he is credited with transforming the company from a struggling memory chip maker into the processor powerhouse it is today. He was Time’s ‘Man of the Year’ in 1997 and he was a widely revered figure in Silicon valley.
But the path to success was not easy.
Having survived prostate cancer in 1995, Grove was diagnosed with Parkinson’s in 2000. Viewing the situation as a problem solving exercise, he poured tens of millions of his own money into researching Parkinson’s.
Andy & Michael J Fox. Source: MJFF
But coming from the world of ‘Moore’s Law’, Grove became frustrated by a.) the slow speed of progress in the world of biomedical research and b.) the tools used to assess it.
In particular, he disliked the UPDRS, which he referred to as a “piece of crap” (Source – you should read the linked article).
What is the UPDRS?
It is often said that Parkinson’s is a ‘distinctly human’ condition. Researchers will write in their reports that other animals do not naturally develop the features of the condition, even at late stages of life.
But how true is this statement?
Recently, some research has been published which brings into question this idea.
In today’s post, we will review these new findings and discuss how they may provide us with a means of testing both novel disease modifying therapies AND our very notion of what Parkinson’s means.
Checking his Tinder account? Source: LSE
Deep philosphical question: What makes humans unique?
Seriously, what differentiates us from other members of the animal kingdom?
Some researchers suggest that our tendency to wear clothes is a uniquely human trait.
The clothes we wear make us distinct. Source: Si-ta
But this is certainly not specific to us. While humans dress up to ‘stand out’ in a crowd, there are many species of animals that dress up to hide themselves from both predator and prey.
A good example of this is the ‘decorator crab’ (Naxia tumida; common name Little seaweed crab). These creatures spend a great deal of time dressing up, by sticking stuff (think plants and even some sedentary animals) to their exoskeleton in order to better blend into their environment. Here is a good example:
Many different kinds of insects also dress themselves up, such as Chrysopidae larva:
Dressed for success. Source: Bogleech
In fact, for most of the examples that people propose for “human unique” traits (for example, syntax, art, empathy), mother nature provides many counters (Humpback whales, bower birds, chickens – respectively).
So why is it that we think Parkinson’s is any different?
Wait a minute. Are there other animals that get Parkinson’s?
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 February 2019.
The post is divided into seven parts based on the type of research:
So, what happened during February 2019?
In world news:
31st January – Not exactly February I know, but this is amazing: Forget everything you know about 3D printing, because now we can 3D print with light! (Click here for the research report and click here for the press release).
3rd February – Pope Francis visited Abu Dhabi, in the United Arab Emirates. He is the first pope to visit the Arabian Peninsula.
19th February – Star Wars Lightsaber duelling was registered as an official sport in France, as part of an effort to encourage young people to engage more in sports (Click here to read more about this).
21st February – Israeli tech firm SpaceIL launched the Beresheet probe – the world’s first privately financed mission to the Moon. The company is competing in the Google Lunar X Prize, and it is hoping that the craft will land on the surface of the moon on the 12th April.
22nd February – “Wallace’s giant bee” (Megachile pluto) was the world’s largest species of bee – with a wingspan measuring more than six centimetres (2.5 inches) – until the species disappeared in 1981. An international team of scientists and conservationists have now re-discovered it in an Indonesian rainforest, giving hope that other lost species may also be found.
In the world of Parkinson’s research, a great deal of new research and news was reported:
In February 2019, there were 696 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (1555 for all of 2019 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 7 pieces of Parkinson’s news
Today – 27th February, 2019 – the long-awaited results of the Phase II GDNF clinical trial were published.
GDNF (or glial cell line-derived neurotrophic factor) is a protein that our bodies naturally produce to nurture and support cells. Extensive preclinical research suggested that this protein was particularly supportive of dopamine neurons – a group of cells in the brain that are affected by Parkinson’s.
The results of the Phase II clinical trial suggest that the treatment was having an effect in the brain (based on imaging data), but the clinic-based methods of assessment indicated no significant effect between the treatment and placebo groups.
In today’s post we will look at what GDNF is, review the previous research on the protein, discuss the results of the latest study, and look at what happens next.
And be warned this is going to be a long post!
Boulder, Colorado. Source: Rps
It all began way back in 1991.
George H. W. Bush was half way into his presidency, a rock band called Nirvana released their second album (‘Nevermind’), Michael Jordan and the Chicago Bulls rolled over the LA Lakers to win the NBA championship, and Arnold Schwarzenegger’s ‘Terminator 2’ was the top grossing movie of the year.
But in the city of Boulder (Colorado), a discovery was being made that would change Parkinson’s research forever.
In 1991, Dr Leu-Fen Lin and Dr Frank Collins – both research scientists at a small biotech company called Synergen, isolated a protein that they called glial cell-derived neurotrophic factor, or GDNF.
And in 1993, they shared their discovery with the world in this publication:
Title: GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.
Authors: Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F.
Journal: Science, 1993 May 21;260(5111):1130-2.
For the uninitiated among you, when future historians write the full history of Parkinson’s, there will be no greater saga than GDNF.
In fact, in the full history of medicine, there are few experimental treatments that people get more excited, divided, impassioned and evangelical than GDNF.
This ‘wonder drug’ has been on a rollercoaster ride of a journey.
What exactly is GDNF?
An important aspect of developing new potentially ‘curative’ treatments for Parkinson’s is our ability to accurately test and evaluate them. Our current methods of assessing Parkinson’s are basic at best (UPDRS and brain imaging), and if we do not improve our ability to measure Parkinson’s, many of those novel treatments will fail the clinical trial process and forever remain just “potentially” curative.
The ideal method of monitoring Parkinson’s would be a device that requires little effort from the individual being monitored, is completely non-intrusive in their daily living, and is continually collecting information.
In today’s post, we will explore the potential of the Ōura ring.
Harry’s first appearance on the SoPD. Source: Bild
Prince Harry has one and I want it.
A smart, ginger beard?
An Ōura ring.
What is an Ōura ring?
Only the best interesting thing to come out of Finland since… um… hang on… give me a second… to google search… for… something… Finnish. Oh yeah: Nokia mobile phones, the Linux operating system, and person-to-person text messaging (Radiolinja, 1993).
Very techinically minded those Finnish folk!
And the Ōura ring is an EXTREMELY clever piece of technology that simply sits on your finger.
But what does the Ōura ring do?