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Tiny variations our DNA can have a significant impact on our lives.
For the last 20 years, Parkinson’s researchers have been collecting data highlighting ‘genetic risk factors’ that are associated with increasing one’s risk of developing the condition.
More recently, however, these same scientists have started shifting their attention to the factors that modulate these genetic risk factors – and some of those influences are also genetic.
In today’s post, we will look at new research exploring genetic variations that influence the effect of the Parkinson’s-associated GBA genetic variants, and discuss why this research has huge implications not only on how we conduct clinical trials, but also on how we will treat Parkinson’s in the future.
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Prof Craig Venter. Source: ScienceMag
In June 2000, when the results of the first human genome sequencing were announced during a ceremony at the White House, the DNA sequencing pioneer Prof Craig Venter observed that “The concept of race has no genetic or scientific basis“.
He was suggesting that due to genetic variations among human individuals and populations, the term ‘race’ cannot be biologically defined. There was simply no evidence that the broad groups we commonly refer to as “races” have any distinct or unifying genetic identities (Click here for interesting additional reading on this).
Prof Venter’s words were a powerful statement regarding the incredible variability within our genetic make up.
And that variability is even more remarkable considering that we are all 99.9 percent genetically identical.
So how do we explain the variability then?
Canadian scientists recently reported that mice with a specific genetic variation – in the Parkinson’s-associated LRRK2 gene – differ in how they are able to deal with bacterial and viral infections.
Curiously, mice with the Parkinson’s-associated LRRK2 mutation could handle a bacterial infection better than normal mice, while mice with no LRRK2 protein struggled against the infection. And the researchers found that this effect was most prominent in female mice in particular.
And curiously, when the mice are infected with a dangerous virus, female mice with the Parkinson’s-associated LRRK2 mutation fared worse than their male counterparts.
In today’s post, we will discuss what LRRK2 is, review the new research, and explore what the sex difference could mean in terms of Parkinson’s.
Autumn colours. Source: Visitsunlimited
I am a big fan of Autumn.
The colours and the crisp/bracing air. I love the long, slow afternoon strolls and anticipation of the festive season to come.
But most of all I love the license to eat all the good wintery food. After a summer of salads and light food, there is nothing better that entering a warm cottage or pub, and smelling the hearty food (my wife if French – we navigate based on the quality of eateries).
Autumn bliss. Source: Askdrake
But there is a down side to autumn: The start of the flu season.
Luckily, our immune systems are pretty robust – doing battle on a moment-to-moment basis with all manner of pathogenic agents.
Recently, some Canadian scientists discovered something interesing about the immune system and it relates to Parkinson’s.
What did they find?
In previous posts, we have discussed some of the potential benefits of knowing your genetic status with regards to Parkinson’s. For example, knowing if you have a certain genetic risk factor could make eligible for taking part in a particular clinical trial.
There may, however, also be some benefits in NOT knowing your genetic status.
New research suggests that simply learning of a genetic risk can alter one’s physiology.
In today’s post, we will review the results of this new research and discuss what it could mean for the Parkinson’s community.
When I was a kid, I thought I was superman.
Then one of the adult figures in my life told me that I wasn’t.
And all of a sudden I lost my ability to fly.
Many years have gone by now, and its only recently that I’ve discovered that that person was actually wrong: I am Superman.
But curiously my powers of levitation have not (yet) returned…
The power of suggestion has always amazed me. Whether it is based on what others tell us, or on what we tell ourselves, it is truly wonderous the enormous impact some of the information we are given has on our lives. We seemingly get told something and quite often it is just accepted as gospel.
But as we take in that information, there can also be consequences (perceived or otherwise) resulting from that knowledge. And this can have important implications for us and how we interact with the world. In fact, some information that we absorb can affect our very physiology.
Can you give me an example?
In this post, I will address a question that I get asked a lot: What would you do if you were diagnosed with Parkinson’s today?
Before we start, please understand that there is no secret magical silver bullet to be discussed in the following text. Such a thing does not exist, and anyone offering such should be treated with caution.
Rather, in this post I will spell out some ideas (or a plan of attack) of what I would consider doing if I was confronted with a diagnosis today and how I would approach the situation.
An email I received this week:
Love the website. I think you are amazing and I love your dreamy eyes and perfect hair.
[ok, I may be exaggerating just a little bit here]
Given everything that you have read about Parkinson’s, what would you do if you were diagnosed with Parkinson’s today?
I get this kind of correspondence a lot, and you will hopefully understand that I am very reluctant to give advice on this matter, primarily for two important reasons:
- I am not a clinician. I am a former research scientist who worked on Parkinson’s for 15 years (and now help co-ordinate the research at the Cure Parkinson’s Trust). But I am not in a position to be giving medical/life advice.
- Even if I was a clinician, it would be rather unethical for me to offer any advice over the internet, not being unaware of the personal medical history/circumstances in each case.
While I understand that the question being asked in the email is a very human question to ask – particularly when one is initially faced with the daunting diagnosis of a condition like Parkinson’s – this is not an email that I like to receive.
I am by nature a person who is keen to help others, but in this particular situation I simply can’t.
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.
Moving forward into 2019 and beyond, we are going to be getting more sophisticated and targetted with our clinical trials for Parkinson’s. We are gradually moving away from the days when a drug was tested on anyone in the Parkinson’s-affected community, and heading for an age of sub-type specific treatments (Click here for a previous SoPD post on subtyping efforts for PD).
As part of this shift, there are a series of ongoing studies that are trying to identify not only the clinical & biological characteristics of those Parkinson’s sub-types, but also individuals who may already be in those groupings.
One such study is called “Rapsodi” – and it is focused on the identification of people with a particular genetic risk factor of PD – the GBA gene – who also demonstrate the early signs of Parkinson’s.
In today’s post, we will discuss what GBA is, how it is associated with Parkinson’s, and why the Rapsodi study is worthy of the PD community’s attention.
Ambroxol. Source: Skinflint
The clinical trial of Ambroxol in Parkinson’s that has been conducted in London (UK) is close to announcing their final results. The Ambroxol study report should be published in early 2019.
What is the ambroxol study?
Started in February 2017, the Ambroxol study (named AiM-PD – Ambroxol in Disease Modification in Parkinson Disease) is a phase IIA prospective, single-centre, open label clinical trial to evaluate the safety, tolerability and pharmacodynamic effects of Ambroxol in Parkinson’s (Click here to read more about this trial and click here for the press release announcing the start of the study).
This trial, which is funded by the Cure Parkinson’s Trust and the Van Andel Research Institute (USA), has been conducted at the Royal Free Hospital in London (UK). The study has involved 20 people with Parkinson’s self-administering Ambroxol (in 60 mg per tablet) over a 6 month time frame. The participants were given 5 escalating doses of the drug for the first few weeks of the study (from 60 mg three times per day, gradually building up to 420 mg three times a day after the first month of the study).
But hang on a second. What is exactly is Ambroxol?
The Parkinson’s research community is currently drowning in data related to genetics.
It feels like every time one comes up for air, there is a new study highlighting not one, but half a dozen novel genetic variants associated with an increased risk of developing the condition. This week alone, a new research report has been made available that by itself proposes 39 new genetic risk factors.
The researchers analysed the DNA of 37,700 people with Parkinson’s and 1.4 million (!!!) healthy control subjects and found a total of 92 genetic risk factors for PD.
But what does it all mean? How much influence does genetics have on Parkinson’s?
In today’s post, we will outline the genetics of Parkinson’s, review some of the new studies, and discuss what the new findings mean for Parkinson’s.
When I say the word ‘mutant’, what do you think of?
Perhaps your imagination drifts towards comic book superheroes or characters in movies who have acquired amazing new super powers resulting from their bodies being zapped with toxic gamma-rays or such like.
Alternatively, maybe you think of certain negative connotation associated with the word ‘mutant’. You might associate the word with terms like ‘weirdo’ or ‘oddity’, and think of the ‘freak show’ performers who used to be put on display at the travelling carnivals.
Circus freak show (photo bombing giraffe). Source: Bretlittlehales
In biology, however, the word ‘mutant’ means something utterly different.
What does ‘mutant’ mean in biology?
Each time a cell divides, the DNA inside the resulting pair of cells has changed slightly. These small alterations – known as genetic mutations – provide a method by which an organism can randomly determine traits that may be beneficial.
New research indicates that in certain parts of the brain, post-mitotic (non-dividing) cells are taking on as many as one mutation per week across the span of our lives. This results in thousands of genetic variations accumulating in each cell by the time we eventually pass away in old age.
In today’s post we will review new research and consider what this gradual build up of genetic mutations could mean for our understanding of neurodegenerative conditions, like Parkinson’s.
Coming from the back waters of third world New Zealand, you will understand that sheep hold a very special place in my heart.
I grew up a simple country lad, and each year I had a pet lamb that I would raise and train to do silly tricks in the hope of impressing the judges at the annual agricultural/farm day at school. In addition to instilling me with a crazy fanaticism for the sport (read: religion) of rugby, my parents figured that having a pet lamb each year would teach me a sense of responsibility and a sort of discipline.
I’m not really sure how this practice has influenced my later life, but I certainly do have very fond memories of those early years (the first lamb was named ‘Woolly’, the 2nd lamb was named ‘Woolly2’, the third lamb was actually a goat – bad lambing season – which I named ‘Billy the kid’, the 4th lamb was named ‘MacGyver’,…).
Lots of happy memories.
But as I grew into the teenage years, there was one thing that really bothered me with regards to my pet lambs.
It was that whole negative stigma associated with the ‘black sheep’.
Why, I would wonder, was it the ‘black sheep of the family’ that was the bad kid? And why was the one black sheep in every flock considered the worst of the bunch?
Why was this association applied to sheep?
Why not dogs? Or cows? Why do we pick on sheep?
In 2018, there is one particular clinical trial that I will be watching, because the drug being tested could have a big impact on certain kinds of Parkinson’s.
The clinical trial is focused on people with cancer and they will be treated with a drug called TVB-2640. TVB-2640 is an inhibitor of an enzyme called fatty acid synthase (or FAS).
In today’s post we will discuss why TVB-2640 might be a useful treatment for certain kinds of Parkinson’s.
Mitochondria and their location in the cell. Source: NCBI
Regular readers of this blog are probably getting sick of the picture above.
I use it regularly on this website, because a.) it nicely displays a basic schematic of a mitochondrion (singular), and where mitochondria (plural) reside inside a cell. And b.) a lot of evidence is pointing towards mitochondrial dysfunction in Parkinson’s.
What are mitochondria?
Mitochondria are the power stations of each cell. They help to keep the lights on. Without them, the party is over and the cell dies.
How do they supply the cell with energy?
They convert nutrients from food into Adenosine Triphosphate (or ATP). ATP is the fuel which cells run on. Given their critical role in energy supply, mitochondria are plentiful (some cells have thousands) and highly organised within the cell, being moved around to wherever they are needed.
What does this have to do with Parkinson’s?
New research published in the last week provides further experimental support for numerous clinical trials currently being conducted, including one by the biotech company Sanofi Genzyme.
Researchers have demonstrated that tiny proteins which usually reside on the outer wall of cells could be playing an important role in the protein clustering (or aggregation) that characterises Parkinson’s.
In today’s post we will look at this new research and discuss what it could mean for the on going clinical trials for Parkinson’s.
The proverb ‘When the cat is away, the mice will play’ has Latin origins.
Dum felis dormit, mus gaudet et exsi litantro (or ‘When the cat falls asleep, the mouse rejoices and leaps from the hole’)
It was also used in the early fourteenth century by the French: Ou chat na rat regne (‘Where there is no cat, the rat is king’).
And then Will Shakespeare used it in Henry the Fifth(1599), Act I, Scene II:
Westmoreland, speaking with King Henry V, Gloucester, Bedford, Exeter and Warwick
“But there’s a saying very old and true,
‘If that you will France win,
Then with Scotland first begin:’
For once the eagle England being in prey,
To her unguarded nest the weasel Scot
Comes sneaking and so sucks her princely eggs,
Playing the mouse in absence of the cat,
To tear and havoc more than she can eat”
Interesting. But what does any of this have to do with Parkinson’s?