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?
“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?
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?
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?
At 9am on the 30th January, 2019, the Australian Government Federal Health Minister Greg Hunt announced the initiation of the ‘Australian Parkinson’s Mission‘ – a very massive $30 million clinical trial programme that will be focused on potentially disease modifying treatments for Parkinson’s.
This huge endeavour will being with a large multi-arm study – involving 300 hundred participants and investigating 4 drugs (compared to a single placebo). It will be a first of its kind project in the world targeting Parkinson’s.
This is a very exciting development for the Parkinson’s community!
In today’s post, we will discuss what we currently know about the Australian Parkinson’s Mission project, what we hope to see resulting from the initiative, and why this is a tremendous step forward for the international Parkinson’s community as a whole.
Being a patriotic kiwi there is always enormous potential to make fun when writing a post about any Parkinson’s-related news coming out of Australia. New Zealand and Australia have always had a big brother/little brother kind of relationship (and just so we are clear: NZ is the big brother!).
But today is different.
It is very strange to say, but… today… I am actually very proud of you Australia.
At 9am this morning at the Garvan Institute of Medical Research in Sydney, Greg Hunt – the Federal Health Minister of the Australian Government – announced the commencement of a major clinical trial initiative (named ‘The Australian Parkinson’s Mission‘), which is going to be a very large, world-leading clinical programme focused on potentially disease modifying drugs for Parkinson’s (Click here to read the press release).
Struth mate!!! This sounds fantastic. What do we know about the study?
The year 2018 was the 20th anniversary of the discovery of the second genetic risk factor to be associated with Parkinson’s. In 1998, researchers reported that variations in a region of DNA called PARKIN were associated with an early onset form of the condition.
Early onset PARKIN-associated Parkinson’s, however, is rather different to other forms of the condition. For example, the PARKIN version appears to be largely isolated to the loss of dopamine neurons. In addition, it has limited involvement of the Parkinson’s-associated protein alpha synclein.
Recently, researcher and advocates have written a very thought provoking report pointing out these differences and and given the nature of this form of Parkinson’s, they have asked the question, why not conduct a cell transplantation clinical trial in people with early onset PARKIN-associated Parkinson’s?
It’s a really good question.
In today’s post, we will discuss what PARKIN is, what early onset PARKIN-associated Parkinson’s looks like, and why these researchers and advocates are on to a good idea.
This is Martin Taylor.
Husband, father, patriotic Scotsman, and die-hard Hearts supporter (the crazy fool).
In addition, Martin is a prominent Parkinson’s advocate.
Diagnosed in December 2014 with young onset Parkinson’s at age 32, Martin has chosen not to rest on his laurels, and has become a very active member of the Parkinson’s community, being involved with the very dynamic Edinburgh Parkinson’s Research Interest Group, and in 2017 he started the Facebook Parkinson’s Research Interest Group (or PRIG) which now has 2100+ members (including yours truly).
Martin is also a co-author of a very interesting article recently published in the European Journal of Neuroscience:
Title: Are PARKIN patients ideal candidates for dopaminergic cell replacement therapies?
Authors: Kunath T, Natalwala A, Chan C, Chen Y, Stecher B, Taylor M, Khan S, Muqit MMK.
Journal: Eur J Neurosci. 2018 Dec 26.
PMID: 30586214 (This report is OPEN ACCESS if you would like to read it)
Note: This article is part of a special edition tribute to Tom Isaacs (co-founder of the Cure Parkinson’s Trust), and there are a number of very interesting OPEN ACCESS articles in that issue.
In their article, the authors propose that individuals with early onset Parkinson’s that is associated a PARKIN genetic variant are the ideal candidates for cell transplantation therapy.
Interesting. Tell me more. But what is a PARKIN genetic variant?
Recent analysis of blood samples collected during the Phase II clinical trial of Exenatide in Parkinson’s has uncovered a very interesting finding that could have major implications for not only Parkinson’s, but for many different neurological conditions.
Exenatide is a treatment that helps to control glucose levels in people with diabetes. More recently, however, it has been suggested that this drug may also have beneficial effects in Parkinson’s. A collection of clinical trials in Parkinson’s are currently unway to test this idea.
The researchers who conducted a Phase II clinical trial of Exenatide in Parkinson’s have analysed ‘exosomes‘ collected from the blood of participants, and they found something rather remarkable.
In today’s post we will discuss what exosomes are, what the researchers found, and why their discovery could have major implications for all of neurological research.
This week, however, researchers involved in the study reported yet another really interesting finding from the trial. And this one could have profound consequences for how we study not only Parkinson’s, but many other neurological conditions.
What did they find?
Last week this report was published:
Title: Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial.
Authors: Athauda D, Gulyani S, Karnati H, Li Y, Tweedie D, Mustapic M, Chawla S, Chowdhury K, Skene SS, Greig NH, Kapogiannis D, Foltynie T.
Journal: JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4304. [Epub ahead of print]
In the Exenatide Phase II clinical trial, 60 people with moderate Parkinson’s were randomly assigned to receive either 2mg of Exenatide or placebo once weekly for 48 weeks followed by a 12-week washout (no treatment) period. The results suggested a stablisation of motor features over the 48 weeks of the study in the treated group (while the condition in the placebo group continued to progress).
During the study (which was conducted between June 2014 – June 2016), blood samples were collected at each assessement.
From those blood samples, serum was collected and analysed.
Remind me again, what is serum?
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 December2018.
The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos).
So, what happened during December 2018?
In world news:
7th December – The U.N.’s International Telecommunication Union reported that, by the end of 2018, more than half – a full 51.2 percent – of the world’s population will be using the Internet (Click here to read more about this).
8th December – Drama at the 24th Conference of the Parties to the United Nations Framework Convention on Climate Change (COP24) meeting in Katowice, Poland. The US, Saudi Arabia, Russia and Kuwait object to adopting the scientific report – which was commissioned at the 2015 meeting. The study suggests that the world is now “completely off track” on climate change, heading towards a 3 degree C. rise by the end of this century rather than a mere 1.5 degree C. rise (Click here to read more about this).
12th December – Negotiators at COP24 in Katowice finally secured an agreement on a range of measures that will make the Paris climate pact operational in 2020 (Click here to read more about this).
17th December – Astronomers announced that they have identified the most distant object ever observed within our solar system. Currently named “2018 VG18” (but nicknamed ‘Farout’), the 500km (310 miles) wide body is approximately is 120 times further away from the sun than Earth is (to put that in perspective, Pluto is only 34 times – Click here to read more about this).
In the world of Parkinson’s research, a great deal of new research and news was reported:
In December 2018, there were 597 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (7672 for all of 2018 – compared to 7675 for all of 2017….seriously?!? Just 3 papers difference?!?). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).
The top 5 pieces of Parkinson’s news
There is a great deal of interest in genetic risk factors in Parkinson’s at the moment. A number of companies are providing direct-to-consumer services which provide individuals with some information about their family history and whether they have any of the more common genetic variations that are associated with medical conditions, like Parkinson’s.
Recently a new genetic data company has started – called Nebula Genomics – and they are offering a slightly different kind of service.
While many of the direct-to-consumer genetic companies have a business model that involves selling on genetic information to third parties, Nebula is offering a more patient-empowering option.
In today’s post, we will discuss the genetics of Parkinson’s, what Nebula Genomics is offering, and how this new service could be useful for the Parkinson’s community.
Prof George Church. Source: Biospace
Professor George Church is a person most readers will have never heard of.
He is the Robert Winthrop Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT, and was a founding member of the Wyss Institute for Biologically Inspired Engineering at Harvard.
He has co-author of over 500 academic papers, 143 patents and co-founded 22 biotech companies. In addition, he has participated in technology development, advising most of the major Genetic Sequencing companies, and he has been at the forefront of genetic research since the 1980s when he was involved with setting up the Human Genome Project.
His impact in the world of genetics has been tremendous.
But Prof Church is also something of a maverick. A left-field thinker. A disrupter.
He is a great supporter of open access genome sequencing and shareable human medical data. He is also keen to bring back extinct species, such as the Woolly Mammoth (Click here for more on this idea).
The return of the woolly mammoth. Source: Phys
Most recently, however, his name has been associated with a new company called Nebula Genomics.