“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?
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
The SoPD has a policy of not advertising or endorsing products/services.
This rule is in place to avoid any ethical/conflict of interest situations. It does little, however, to stop folks from bombarding the comments sections with links for wondrous magical cures which probably involve more ‘magical’ than actual cure.
Having said all that, every now and then I find or read about something that I think may be of interest to readers. In many of those cases, I can not vouch for the information being provided, but where I think there is the potential for readers to benefit, I am happy to take a chance and share it.
Today’s post is all about one such case: The European Parkinson Therapy Centre
Until very recently, I was working in Parkinson’s research centre in Cambridge (UK).
I conducted both lab- and clinic-based research on Parkinson’s in the lab of Prof Roger Barker. And it was in the clinic – several years ago – that I started hearing about a mysterious place that was not offering ‘to cure’ people of Parkinson’s, but rather helping them to live a better life with the condition.
Initially it was just a trickle of questions:
“Have you ever heard of this therapy place in Europe for people with Parkinson’s?” (“Nope, sorry” was my response).
But then an individual came in for their assessment, and spoke with tremendous enthusiasm about their own personal experience of visiting “this wonderful place in Italy” (“Sounds very interesting,” was my response, “Tell me more“).
Gradually, more and more people started sharing their own stories with me (both in the clinic, at support group meetings, and via correspondence to the SoPD website) about the place in Italy. And eventually it all led to me making some inquiries about the European Parkinson Therapy Centre.
What is the European Parkinson Therapy Centre?
Lipids are ‘waxy’ molecules that make up a large proportion of your brain and they play very important roles in normal brain function. For a long time researchers have also been building evidence that lipids may be involved with neurodegenerative conditions as well.
Recently, new research was presented that supports this idea (in the case of Parkinson’s at least), as two research groups published data indicating that certain lipids can influence the toxicity of the Parkinson’s associated protein alpha synuclein.
One of those research groups was a biotech company called Yumanity, and they are developing drugs that target the enzymes involved with the production of the offending lipids.
In today’s post, we will look at what lipids are, what the new research suggests, and discuss some of the issues that will need to be considered in the clinical development of these lipid enzyme inhibitors.
Yummy. Source: Healthline
There has been the suggestion from some corners that this association may be due to the richness of monounsaturated fats in the foods generally included in this diet.
For example, olive oil is rich in monounsaturated fat.
What are monounsaturated fats?
Mmmm, before I answer that we need to have a broader discussion about “what is fat?“.
Fat is one of the three main macronutrients (carbohydrate and protein being the other two) that the body requires for survival.
Fat serves as a ready source of energy for the body and can also provide insulation against cold temperatures or compression. All fats are derived from combinations of fatty acids (and also glycerol).
What are fatty acids?
A fatty acid is simply a chain of hydrocarbons terminating in a carboxyl group (having a carbonyl and hydroxyl group both linked to a carbon atom). Don’t worry too much about what that means, just understand that fatty acids are basically chains of hydrocarbons that look like this:
A chain of hydrocarbons ending in a carboxyl group (right). Source: Wikipedia
Fatty acids come in two forms:
In the case of a saturated fat, each carbon molecule in the chain of hydrocarbons is bonded to two other carbons by a single bond. Whereas in the case of a saturated fat, one or more carbon molecule in the chain of hydrocarbons is bonded to another carbon molecule by a double bond. For example:
Saturated fatty acids vs unsaturated fatty acids. Source: Medium
And unsaturated fatty acids can be further divided into:
- Monounsaturated fatty acids (or MUFAs) are simply fatty acids that have a single double bond in the fatty acid chain with all of the remainder carbon atoms being single-bonded.
- Polyunsaturated fatty acids (or PUFAs) are fatty acids that have more than one double bond.
OK, but how might monounsaturated fats be involved with Parkinson’s?
That, dear reader, is the focus of numerous studies in the field of lipidomics.
What is lipidomics?
Biotech firm Denali announced the dosing of the first person in their Phase Ib clinical study of their experimental treatment for Parkinson’s called DNL201.
DNL201 is an inhibitor of a Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (LRRK2).
In Parkinson’s, there is evidence that LRRK2 is over activate, and by inhibiting LRRK2 Denali is hoping to slow the progression of Parkinson’s.
In today’s post, we will discuss what LRRK2 is, what evidence exists for DNL201, and what the new clinical trial will involve.
Founded in 2013, by a group of former Genentech executives, San Francisco-based Denali Therapeutics is a biotech company which is focused on developing novel therapies for people suffering from neurodegenerative diseases. Although they have product development programs for other condition (such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease), Parkinson’s is their primary interest.
And their target for therapeutic effect?
The Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (or LRRK2).
What is LRRK2?