“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?
This week the ‘Michael J. Fox Foundation for Parkinson’s Research’ and ‘The Silverstein Foundation for Parkinson’s with GBA’ announced that they are collaboratively awarding nearly US$3 million in research grants to fund studies investigating an enzyme called beta glucocerebrosidase (or GCase).
Why is this enzyme important to Parkinson’s?
In today’s post, we will discuss what GCase does, how it is associated with Parkinson’s, and review what some of these projects will be exploring.
This is Jonathan Silverstein.
He is a General Partner of Global Private Equity at OrbiMed – the world’s largest fully dedicated healthcare fund manager. During his time at OrbiMed, the company has invested in healthcare companies that have been involved with over 60 FDA approved products.
In February 2017 – at just 49 years of age – Jonathan was diagnosed with Parkinson’s.
Rather than simply accepting this diagnosis, however, Mr Silverstein decided to apply the skills that he has built over a long and successful career in funding biotech technology, and in March 2017, he and his wife, Natalie, set up the Silverstein Foundation for Parkinson’s with GBA.
The foundation has just one mission: “to actively pursue and invest in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in GBA mutation carriers”
And it seeks to address this by achieving three goals:
- to find a way to halt the progression of Parkinson’s with GBA.
- to identify regenerative approaches to replace the damaged/lost cells
- to find preventative measures
This week, the Silverstein foundation and the Michael J. Fox Foundation for Parkinson’s Research made a big anoouncement.
The two organisations announced nearly US$3 million in grants to fund studies investigating an enzyme called glucocerebrosidase beta acid (or GCase).
And what exactly is glucocerebrosidase?
The clinical testing new compounds is horrifically slow. There is simply no easy way to word it. From lab bench to regulator approval, we are currently looking at a process which will take at least a decade.
The repurposing of clinically available treatments has shortened this process, but there are a limited number of drugs that can be repurposed, and the periods of time between clinical trials is still too long.
Acknowledging this situation, we can do one of two things: Accept the circumstances and carry on doing things the way we have always done it (hoping that it will be different next time – a la Einstein’s definition of insanity),… OR we can try to change it.
In today’s post, we will discuss an interesting project that is seeking to do the latter.
The guy at the podium (and in the upper left inset) is Barry Chandler.
A few months ago, Barry came to me and asked “What can I do to help?”
And I replied by asking “What do you do?”
Two things you need to know about Barry:
- He was diagnosed with young onset Parkinson’s 6 years ago, and
- He is a very well connected guy.
VERY well connected!
I am the green string. Barry is everything else. Source: Philiphemme
By day, Barry works in the city of London as a DevOps practitioner (that was a new one for me too – “a combination of cultural philosophies, practices, and tools that increases an organization’s ability to deliver applications and services at high velocity“). But in the evenings and on weekends, Barry is an events co-ordinator.
And these two worlds merge nicely in the form of a meetup group that Barry runs, called “SEAM”.
What is SEAM?
Recently researchers have proposed an interesting idea for why Parkinson’s is a distinctly human condition: There are parts of our brains that have not kept up with evolution, and as we live longer those areas become strained which ultimately results in the features of Parkinson’s.
It’s a really interesting idea – one which could have major implications.
In today’s post, we will review the new proposal and consider how we could use it in our approach to therapeutic interventions.
2020 Tesla Roadster. Source: Motortrend
By nature and design, I am not a car person.
If I can actually fit in the car (I am rather tall) and it gets me from A to B, it’s a great car. I don’t really care what it looks like, because I usually look ridiculous in the more sporty versions (my knees up around my ears…). As long as it gets from A to B, I’m happy.
Having said that, I do appreciate the technological advancements that are being made by companies like Tesla (I mean seriously, their Roadster – pictured above – is an electric car that does 0-60 mph in 1.9-seconds, quarter-mile in less than 9-second, a 250-plus-mph top speed, and an all-electric range of 620-mile! All of those statistics are incredible!).
It is amazing the evolutionary process that automobiles have gone through.
The first petrol engine-propelled car invented by Karl Benz. Source: Oxfordsurfaces
Every aspect of these vehicles has changed over time. From the wheels to the engine and from petrol to electric based cars, each component has been adapted across the decades to keep up with the needs of its environment.
Researchers are now wondering if the same can be said for our brains. And just recently some scientists have questioned whether some evolutionary design faults could explain why humans develop Parkinson’s.
What?!? What do you mean?
In today’s post we are going to look at a recent piece of research that suggests some of the bacteria in our gut can influence the availability of the medication we use to treat Parkinson’s.
In addition, we will look at a novel way researchers are re-engineering bacteria in the gut to correct other medical conditions (such as phenylketonuria) and we will ask if the same can not be applied to Parkinson’s.
The Platypus. Source: National geographic
The interesting, but utterly useless fact of the day: The duck-billed Platypus of Australia does not have a stomach.
No really. These oddities of evolution have no stomach. There’s no sac in the middle of their bodies that secrete powerful acids and digestive enzymes. The oesophagus (the tube from the mouth) of the platypus connects directly to its intestines.
The platypus. Source: Topimage
And believe it or not, platypus are not alone on this ‘sans estomac‘ trend. At least a 1/4 of the fish species on this planet do not have a stomach (Source).
And this absense of the stomach isn’t even remotely weird in the animal kingdom. Some creatures don’t even have a gastrointestinal system. No mouth. No anus. No intestines. Nothing.
The giant tube worm – Riftia pachyptila – lives on the floor of the Pacific Ocean, next to hot hydrothermal vents and can tolerate extremely high levels of hydrogen sulfide (hazardous for you and I). These creatures – which can grow up to 2.4 meters (or 7+ feet) in length – have no gastrointestinal tract whatsoever. Zip, zero, nada.
Rather they have an internal cavity – called a trophosome – filled with bacteria which live symbiotically with them.
Watch this video of Ed Yong explaining it all (great video!):
WOW! Fascinating! But what does ANY of this have to do with Parkinson’s?
Today we received word of a new clinical trial for Parkinson’s being initiated here in the UK. This trial – named the UP study – will evaluate the safety and tolerability of a compound called Ursodeoxycholic acid (or UDCA – click here to read the press release).
UDCA is clinically available medication that is used in the treatment of gall stone, but recently there has been a large body of research suggesting that this compound may also have beneficial effects in Parkinson’s.
In today’s post, we will look at what UDCA is, discuss the preclinical research exploring UDCA, and outline the structure of the new clinical trial.
How often do you consider your gallbladder?
It is one of the less appreciated organs. A pear-shaped, hollow organ located just under your liver and on the right side of your body. Its primary function is to store and concentrate your bile. What is bile you ask? Bile is a yellow-brown digestive enzyme – made and released by the liver – which helps with the digestion of fats in your small intestine (the duodenum).
One of the down sides of having a gall bladder: gallstones.
Gallstones are hardened deposits that can form in your gallbladder. About 80% of gallstones are made of cholesterol. The remaining 20% of gallstones are made of calcium salts and bilirubin. Bilirubin is the yellow pigment in bile. When the body produces too much Bilirubin or cholesterol, gallstones can develop.
Gallstones – ouch! Source: Healthline
About 10-20% of the population have gallstones (Source), but the vast majority experience no symptoms and need no treatment.
Interesting intro, but what does any of this have to do with Parkinson’s or a new clinical trial?
One of the treatments for gallstones is called UDCA. And today we found out that this compound is being clinically tested for “repurposing” as a treatment for Parkinson’s.
What is UDCA?