“In current models of neurodegeneration, individual diseases are defined by the presence of one or two pathogenic protein species. Yet, it is the rule rather than the exception that a patient meets criteria for more than one disease”
These are the first lines of a manuscript on the preprint sharing webiste BioRxiv, which analysed the co-occurance of biological markers of Alzheimer’s or Parkinson’s or other neurodegenerative conditions across 18 brain regions in 1389 postmortem brain from people who passed away with a neurodegenerative condition.
The results are interesting.
In today’s post, we will discuss what this study did, what is meant by “transdiagnostic disease clusters”, and consider what could they mean for our understanding of Parkinson’s… and heck, neurodegenerative conditions in general.
Malcolm Gladwell. Source: Masterclass
I am a fan of Malcolm Gadwell (not an endorsement, this is just me sharing).
He has a great way of looking at a situation from a completely different angle, finding things that no one else sees, and then writing about it in a clever, easy to read manner. Having read most of his books, I was rather pleased to learn that he has a podcast – Revisionist History.
And it’s good.
Oh boy, it’s good.
The first episodes of the most recent series of the podcast have helped to raise my fragile self esteem, because I am definitely a tortoise (just listen to the first two episodes of season 4 and you’ll understand).
Oh, and Mr Gladwell, if you ever read this – in the next series of the podcast, please have a look at the dysfunctional way we clinically test new therapies in medicine – click here to read a previous SoPD rant on this topic. Thanks!
What does Malcolm Gladwell have to do with Parkinson’s?
It all comes back to that idea of looking at a situation from a completely different angle.
What do you mean?
The recent documents filed with the U.S. Securities and Exchange Commission by the biotech firm Prevail Therapeutics provides interesting insight into the bold plans of this company which was only founded in 2017.
Even more recent news that the U.S. Food and Drug Administration (FDA) has accepted the company’s Investigational New Drug (IND) application for its lead experimental treatment – PR001 – suggests that this company is not wasting any time.
PR001 is a gene therapy approach targeting GBA-associated Parkinson’s.
In today’s post, we will discuss what GBA-associated Parkinson’s is, how Prevail plans to treat this condition, and discuss what we know about PR001.
Caterina Fake. Source: TwiT
The title of this post comes is from a quote by Caterina Fake (co-founder of Flickr and Hunch (now part of Ebay)), but it seemed appropriate.
This post is all about dreaming big (curing Parkinson’s), the struggle to get the research right, and to create a biotech company: Prevail Therapeutics.
What is Prevail Therapeutics?
Prevail is a gene therapy biotech firm that was founded in 2017.
Dr Asa Abeliovich. Source: Prevail
It was set up in a collaborative effort with The Silverstein Foundation for Parkinson’s with GBA (Click here to read a previous SoPD post about this organisation) and OrbiMed (a healthcare-dedicated investment firm).
What does Prevail Therapeutics do?
Researchers have recently described a new method to quantify a person’s “immune age” – a measure that could act as a key determinant of future health, as well as response to disease and treatment.
This novel test appears to provide a more reliable predictor for the status of one’s immune system than any other previous method.
And it could be useful in other ways.
In today’s post, we will discuss this new method of determining “immune age”, explore examples of how similar analysis has been used for other conditions, and consider what it could mean for Parkinson’s.
Do you remember Andre Agassi?
I know he’s still around, but when I was young and less beautiful, I was a big fan. Not only of his on court achievements, but also of his charismatic off-court image.
And it certainly paid off well for him:
One of the things that Agassi taught us was that “image is everything”.
Before Agassi, tennis was a conservative sport of white shirts & shorts (McEnroe was basically as radical as things got). It was bland, conservative, and – yes, I’ll say it – boring.
Agassi not only brought colour but charisma to the game. It was shocking and disgraceful to some, but to young, naive fools like me, it was a captivating breath of much needed fresh air.
Despite the early infatuation with the stylings of Mr Agassi, I have to admit that I have never remotely been concerned about own image. My dimensions mean that I wear what fits as opposed to what I like, and as a result the finished product is better behind a keyboard rather than speaking to a crowd.
But as I have gotten older, I have become concerned about a different kind of IMM-AGE (not a typo).
Let me explain: Recently some researchers in Israel and at Stanford University in the US published a rather remarkable research report which if replicated could have important implications for how we approach medical care.
What did they report?
Recent regulator approvals and exciting new preclinical data has refocused attention on a treatment approach for genetic conditions that has travelled a long and winding road towards clinical use.
Antisense oligonucleotides represent a method of altering protein levels at the post transcriptional level – it basically stops certain RNAs from being translated into protein.
And recently, a new clinical trial has been registered which will explore the use of this treatment approach in people with Parkinson’s.
In today’s post, we will look at what antisense oligonucleotides are, how they work, what research has been conducted in the context of Parkinson’s, and some of the limitations of this approach that still exist.
Spinal muscular atrophy (or SMA) is a genetic disorder that results in the degeneration of motor neurons in the spinal cord. This leads to progressive weakening and atrophy of muscules, ultimately leaving sufferers paralysed. It is caused by loss-of-function mutations in the survival motor neuron 1 (SMN1) gene.
It is a terrible condition that starts in very young children and has an incidence approaching 1:10,000 live births.
Luckily, novel therapies are being developed to deal with this condition, and in 2016, the US FDA approved a new treatment – following rather dramatic clinical trial results – called Nusinersen. This new therapy has caused a great deal of excitement as it basically halted the progression of SMA in many cases.
And a recent long term report highlights some of these very impressive results:
Title: Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies.
Authors: Darras BT, Chiriboga CA, Iannaccone ST, Swoboda KJ, Montes J, Mignon L, Xia S, Bennett CF, Bishop KM, Shefner JM, Green AM, Sun P, Bhan I, Gheuens S, Schneider E, Farwell W, De Vivo DC; ISIS-396443-CS2/ISIS-396443-CS12 Study Groups.
Journal: Neurology. 2019 May 21;92(21):e2492-e2506.
PMID: 31019106 (This report is OPEN ACCESS if you would like to read it)
Most importantly, Nusinersen is having real impact on the children who are affected by this condition:
Interesting, but what exactly is Nusinersen?
It is an antisense oligonucleotide.
What are antisense oligonucleotides?
The clustering (or aggregation) of misfolded proteins is a key feature of many neurodegenerative conditions. These aggregating proteins are collectively referred to as ‘amyloid’ proteins, and the way that they have misfolded allows many copies of these proteins to stick together.
Amyloid proteins are associated with more than 50 medical conditions (from Alzheimer’s, ALS, Huntinton’s and Parkinson’s through to rheumatoid arthritis and diabetes).
In addition to being public enemy no. 1 for their respective conditions, amyloid proteins also share another curious feature:
They glow when exposed to specific wavelengths of light (like near-infrared).
In today’s post, we will look at what we mean by ‘amyloid proteins’, what this new research found, and how this property could be extremely useful in the tracking of Parkinson’s over time.
If you have recently sent me an email, you may not have had a response. I apologise profusely for this, but I have gradually become inundated with questions and requests, and have had a hard time keeping up (in addition: family and day job take priority).
I do get some wonderfully titled emails though, which immediately grab the attention.
For example, the other day I recieved an email entitled:
“So, will my head glow in a disco?”
A brief glance at the contents confirmed suspicions that the sender was referring to this new research report:
Title: Ultraviolet–visible–near-infrared optical properties of amyloid fibrils shed light on amyloidogenesis
Authors: Pansieri J, Josserand V, Lee S-J, Rongier A, Imbert D, Sallanon MM, Kövari E, Dane TG, Vendrely C, Chaix-Pluchery O, Guidetti M, Vollaire J, Fertin A, Usson Y, Rannou P, Coll J-L, Marquette C, & Forge V
Journal: Nature Photonics, published 13th May 2019
Previously researchers have described an intrinsic ultraviolet–visible optical property to amyloid proteins.
What does that mean?
Today’s post is a recap of Day 3 – the final day – at the World Parkinson’s Congress meeting in Kyoto, Japan.
I will highlight some of the presentations I was able to catch and try to reflect on what was an amazing meeting.
The final day of the WPC meeting for me started with Parkinson’s advocate Heather Kennedy‘s presentation on “Your radical new life: Creative ways to overcome our challenges”. In her talk, she spoke of the mindset that is required for tackling Parkinson’s and provided some advice on what-to-do and what-not-to-do.
And Heather was speaking from personal experience. Having been diagnosed in 2012, she has become an active advocate, supporter of Davis Phinney and Michael J Fox Foundations, and an administrator on several online sites. And she regularly speaks about different methods for overcoming the challenges of Parkinson’s:
“It is not ‘why is this happening to me?’, it is ‘what is this teaching me?”
Here is a presenation she gave at the recent Parkinson’s Eve meeting in the UK earlier this year:
Key among her pieces of advice is the need to make connections:
Every three years the Parkinson’s community – patients, families, researchers, and clinicians – comes together to learn from each other, discuss where we are, and explore where we should be going.
The World Parkinson’s Congress (or WPC) is a very special event – rather unique in the world of conferences and scientific meetings.
The WPC meeting which is being held in Kyoto is the first one I have attended, and in today’s post, I will share what I observed on Day 0, and my impressions/thoughts of those observations.
The SoPD is at the 2019 World Parkinson’s Congress being held in Kyoto this year.
For the sake of those who are unable to be here, I will endeavour (famous last words coming up) to provide some of my impressions and observations of what is happening at the meeting on each day. We have previously discussed what the World Parkinson’s Congress is (Click here to read that post), so this post is literally just what happened each day.
And this is my first time attending the WPC, so any comments here will be coming from a novice. And I have been told by many individuals that WPC is not like other conferences.
Apparently, WPC is very special.
Earlier this year, a San Francisco-based biotech company – called Cortexyme – published a research report that grabbed my attention.
The study presented data supporting an alternative theory of the cause of Alzheimer’s – one in which a bacteria involved in gum disease appears to be playing a leading role – and evidence that the company’s lead experimental compound COR388 could have beneficial effects in the treatment of the condition.
While the study was intriguing, what completely blew my mind was the fact that the company had already tested COR388 in a couple of Phase I clinical trials, and since then they have initiated a large Phase II/III trial.
In today’s post, we will discuss this new theory of Alzheimer’s, look at what Cortexyme are doing, and how this could relate to Parkinson’s.
The dashed lines show associations. Source: Slideplayer
Before we start today’s post, a word on ‘associations‘.
Please remember while reading this material that association does not equate to causation.
So if I write something like “researchers have found an association between a type of bacteria that causes gum disease and Alzheimer’s”, it does not mean that someone with either condition necessarily has the other. It only means that they have both simply appeared in the same individuals at a higher than chance rate.
So what is today’s post about?
A very interesting report in which researchers have found an association between a type of bacteria that causes gum disease and Alzheimer’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 April 2019.
The post is divided into seven parts based on the type of research:
So, what happened during April 2019?
In world news:
10th April – Scientists from the Event Horizon Telescope project announced the first ever image of a black hole. Located in the core of the Messier 87 galaxy (53 million light years from Earth), this supermassive black hole has a mass 6.5-billion times that of the Sun! The black hole’s boundary – the event horizon – is around 2.5 times smaller than the shadow it casts and measures just under 40 billion km across (about the size of Neptune’s orbit!!!).
10th April – Fossil fragments found in the Callao Cave in the Philippines revealled the existence of a new species of human, Homo luzonensis. The species is named after the island – Luzon – where it was discovered.
15th April – During Holy Week, a devastating fire engulfed the roof and main spire of Notre-Dame Cathedral in Paris.
24th April – I am a big fan of Martin. Several years ago his video of the Marble machine took the internet by storm and since then I have been following his regular vlog updates on the construction of the new and improved Marble machine X. This week he took the new machine for its first test run – still has parts missing, but this is mesmerising to watch. If you don’t follow him you should!
In the world of Parkinson’s research, a great deal of new research and news was reported:
In April 2019, there were 730 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (3134 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 9 pieces of Parkinson’s news
Microglia are the resident immune cells in the brain – they maintain law and order when trouble kicks off. And when things get really bad, these cells change shape, become “activated”, and start to absorb toxins, debris and anything else that they feel should not be there – via a process called phagocytosis.
And they are ruthless in this task.
When we are young, these cells function very well at maintaining a general sense of ‘homeostasis‘ (or stable equilibrium). But as we age,… well, let’s just say things start to slip a little.
Recently a group of researchers at Stanford University have discovered by inhibiting a single protein, called CD22, they can restore microglial homeostasis in the ageing brain, and this had beneficial effects in a model of Parkinson’s.
In today’s post, we will look at what microglia are, what phagocytosis is, and what these new CD22 results could mean for Parkinson’s.
My father often says: Ageing is not for sissies.
And as the birthdays have started to mount up, I’ve come to better understand what he means.
There are days when I feel like an old man trapped in a 27 year old’s body. For the record, I’m 27. And for the record, I’m going to be 27 until I die (27 was a great year!).
An amazing journey. Source: Topsimages
While some are able (and foolishly gleeful) to avoid taxes, until recently no one has been able to escape the rentless march of ageing. Until recently, the vast majority of us have been resigned to our fates. And until recently, the fountain of youth has only existed in the realm of the Hollywood movies.
The force is strong with this one. Source: Reddit
Recently there has been an enormous amount of research focused on stopping ageing and preventing death (both of which are being viewed as “curable diseases” – click here to read more about this). Now to be honest, much of this is still quackery.
But there does seem to be progress being made in the biology of extending ‘healthspan’ (as opposed to lifespan).
And some of that research could have implications for Parkinson’s.