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:
Today’s post is a recap of Day 2 at the World Parkinson’s Congress meeting in Kyoto, Japan.
I will highlight some of the presentations I was able to catch and discuss some of my key take-aways from the day’s activities.
Early meetings meant that I arrived late to the morning session of presentations on the Day 2 (6th June) of the WPC meeting. But luckily I was in time to catch Benjamin Stecher giving his talk in the main hall.
Diagnosed at 29 years of age with young onset Parkinson’s, Ben has spent the last couple of years touring the world requesting meetings with Parkinson’s researchers, to learn more about what they do and what still needs to be done. This quest has give him a unique perspective on the state of Parkinson’s research, and has helped him in his role as an advocate.
I was looking forward to hearing him speak on the main hall stage,…
…and, like everyone else in the room, I was surprised by what he did during his talk.
This post provides an overview of activities on Day 1 at the World Parkinson’s Congress meeting in Kyoto.
After a spectacular opening ceremony the night before, Day 1 began with some impressive keynote presentations. Then came a series of fascinating workshops and roundtables before poster tours and social activities.
In today’s post, we will discuss what happened at day 1 of the WPC meeting.
Following the amazing activities on Day 0 (Click here to read more about that), attendees of the World Parkinson’s Congress woke up to beautiful weather on Day 1.
The date was the 5th June, and the weather was sunny with a humid high of 32 degrees C. (89.6 F).
The first order of business each day at the conference is checking the programme to see what presentations/workshops/lectures/activities you would like to take part in.
This is the WPC meeting programme:
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.
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 May 2019.
The post is divided into seven parts based on the type of research:
So, what happened during May 2019?
In world news:
8th May – A British teenager, Isabelle Holdaway (below), aged 17, was reported to be the first patient ever to receive a genetically modified phage therapy to treat an antibiotic-resistant infection (Click here to read the research report and click here to read the press release).
9th May – The Reserve Bank of Australia acknowledged an unfortunate spelling error (“Responsibil_ty”) on 400 million new $50 notes. There is currently $2.3 billion of these notes in circulations (Click here to read more about this).
May 24 – British Prime Minister Theresa May announced her resignation as Conservative leader, effective 7 June 2019.
30th May – Physicists reported that they have teleported a computer circuit instruction – known as a quantum logic operation – between two separated ions (electrically charged atoms), providing an example of how quantum computer programs could carry out tasks in future large-scale quantum networks (Click here to read more about this, and click here to read the press release).
In the world of Parkinson’s research, a great deal of new research and news was reported:
In May 2019, there were 828 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (3742 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 5 pieces of Parkinson’s news
On 31st May in 2017, Tom Isaacs – one of the co-founder of the the Cure Parkinson’s Trust – passed away suddenly.
It was a terrible shock for the Parkinson’s community, many of whom saw Tom as a leader of advocacy efforts.
In today’s post, two years after his passing, we remember Tom.
In 1996 – at just 27-years of age – Tom Isaacs, a London-based surveyor, was diagnosed with Parkinson’s. After dealing with the initial shock of it all, Tom embraced his situation and became a committed, (utterly) tireless activist.
He firstly walked the entire coastline of the UK to raise money and awareness for Parkinson’s. His book, “Shake well before use“, discusses that trip and his journey in adapting to life with Parkinson’s. It is a wonderful read – not only providing an intimate insight into the trials and tribulations of the condition, but also offering glimpses into the brilliant wit and humor of the man himself.
Upon returning from his epic walk, Tom (along with three other gentlemen with Parkinson’s) founded and set up the Cure Parkinson’s Trust.