New approaches for potentially slowing the progression of Parkinson’s are being announced on a regular basis. Some of them can not be independently replicated (such is the nature of science), while others open up whole new areas of research.
Recently scientists have reported that inhibiting certain aspects of the kynurenine pathway – which plays a critical role in generating energy in cells – can have neuroprotective results in models of Parkinson’s.
Many of the results have been independently replicated and the findings are now resulting in a new class of drug heading for clinical testing.
In today’s post, we will delve into what the kynurenine pathway is, explore how it relates to Parkinson’s, and discuss some of the approaches soon heading for the clinic.
Amino acids are the fundamental building blocks of proteins in biology, but the “essential” label in this case does not refer to its necessity (although it is necessary), but rather the fact that it cannot be made by our bodies. As a result, all essential amino acids must come from the food we consume.
Tryptophan has many functions within the body:
it is a precursor to the neurotransmitter serotonin (which influences your mood, cognition, and behaviour)
it is a precursor of the hormone melatonin (which governs your sleep-wake cycle)
Over the last 20 years, researchers have identified a number of genetic variations that can confer an increased risk of developing Parkinson’s. Tiny alterations in regions of DNA (called genes) – which provide the instructions for making a protein – can increase one’s chances of Parkinson’s.
A better understanding of the biological pathways associated with these genetic risk factors is opening up vast new areas of research.
Recently researchers have been exploring the biology behind one particular genetic risk factor – involving a gene called TMEM175 – and they have discovered something quite unexpected: While one genetic variation in the TMEM175 gene increases the risk of Parkinson’s, another variation reduces it.
In today’s post, we will explore the biology of TMEM175, review what the results of the new research indicate, and consider why these findings might be interesting in terms of potential future therapeutic targets.
Robert Pershing Wadlow was always in the back of school photos.
Born February 22nd 1918, Wadlow’s birth certificate indicated that he was “normal height and weight“, but from that point onwards, there was nothing normal about his rate of growth.
By the time, Robert was 8 years old, he was taller than his father (he was 6 foot/183cm). And eight years later when he turned 16, Robert was 8 foot 1 (2.47 m)… and he was still growing.
Here is a picture of him with his family at 19 years of age:
Robert was the tallest person in recorded history, and at the time of his death – at the tragically young age of 22 – Robert was almost 9 feet tall (8 ft 11; 2.72 m)… and still growing.
His incredible growth was caused by a condition called hyperplasia of his pituitary gland. This condition that results in an overactive pituitary gland which causes an abnormally high level of the human growth hormone to be produced.
Human growth hormone (or somatotropin) is a peptide hormone that belongs to a much larger group of molecules that are referred to as growth factors.
In general terms, growth factors are small molecule that plays an important and fundamental role in biology. They stimulate cell proliferation, wound healing, and occasionally cellular differentiation.
And Robert’s story is an example of how powerful the effect these tiny molecules can have.
Growth factors are secreted from one cell and they float around in the extracellular world until they interact with another cell and initiate survival- and growth-related processes.
We have often discussed growth factors on this website in the past, with posts of growth factors like GDNF (Click here to read a SoPD about this) and CDNF (Click here to read a SoPD post on this). These discussions have largely focused on how growth factors could have neuroprotective and regenerative potential for Parkinson’s, stimulating survival and growth of cells.
Recently, however, new research has been published that demonstrates how some of these growth factors could be influencing an entirely different aspect of cellular biology that is connected to Parkinson’s: lysosomal function.
Cell replacement therapy is a key component of any “cure” for Parkinson’s – replacing the cells that have been lost over the course of the condition.
Cell transplantation of dopamine neurons has a long track record of both preclinical and clinical development and represents the most developed of the cell replacement approaches.
Two weeks ago, the biotech firm BlueRock Therapeutics announced an agreement under which the pharmaceutical company Bayer AG would fully acquire the company.
In today’s post we will discuss why this is major news for the Parkinson’s community and an important development for the field of cell replacement therapy.
On the 8th August, Bayer AG and BlueRock Therapeutics announced an agreement under which Bayer will “fully acquire BlueRock Therapeutics, a privately held US-headquartered biotechnology company focused on developing engineered cell therapies in the fields of neurology, cardiology and immunology, using a proprietary induced pluripotent stem cell (iPSC) platform” (Source).
What is BlueRock Therapeutics?
BlueRock is a biotech firm that was foundered in 2016 as a joint venture between the investment firm Versant Ventures and Leaps by Bayer (with US$225 Million in Series A Financing).
Versant Ventures is a leading venture capital firm that specializes in investing “in game changing biopharmaceuticals, medical devices, and other life science opportunities”. Leaps by Bayer is an effort by the Pharmaceutical company Bayer at “spearheading a movement to make paradigm-shifting advances in the life sciences – targeting the breakthroughs that could fundamentally change the world for the better”.
The news on the 8th August means Bayer will acquire the remaining stake for approximately US$240 million in cash (to be paid upfront) and an additional US$360 million which will be payable upon the achievement of certain pre-defined development milestones.
Given that Bayer currently holds 40.8% stake in BlueRock Therapeutics, this announcement values the company at approximately US$1 billion.
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:
On the 12th and 13th November, Parkinson’s UK held their biennial research conference in York.
It is not only an opportunity for the charity to showcase some of the research that they have funded over the last few years, but it was also a chance for members of the Parkinson’s research community to come together to share ideas, network and form new collaborations.
I was lucky enough to attend the event this year, and wanted to share some of the take away messages from the conference with the readers.
In today’s post, we will review Parkinson’s UK 2018 research conference (#Parkinsons2018).
Parkinson’s UK is the largest Parkinson’s research and support charity in the United Kingdom. Since 2015, they have invested over £18 million in a variety of research projects focused on all aspects of Parkinson’s – from new experimental treatments to the Parkinson’s UK Brain Bank.
Every two years, Parkinson’s UK holds a conference highlighting some of the research that the organisation has funded over the last few years. The meeting is usually held in the beautiful walled city of York – lots of history and narrow streets to explore.
In December of of 2017, the results of a clinical trial suggested that a particular kind of exercise may have beneficial effects against certain aspects of Parkinson’s. Specifically, a high-intensity treadmill regime was found to be ‘non-futile’ as an intervention for the motor symptoms in de novo (newly diagnosed) Parkinson’s.
Recently, however, new pre-clinical research has been published which reported that when mice with particular Parkinson’s-associated genetic mutations are exercised to exhaustion, they have high levels of inflammation which can exaggerate the neurodegeneration associated with that model of PD.
So naturally, some readers are now asking “So should I be exercising or not?!?”
In today’s post we will review the results of the two studies mentioned above, and discuss why exercise is still important for people with Parkinson’s.
Readers are recommended to click on the image above and listen to the music (Michael Sembello’s “Maniac” from 1983) whilst reading this post.
This song was made famous by one particular scene from the 1983 movie “Flashdance” starring Jennifer Beals, in which the lead character undertook an intense dance routine. Ever since that iconic scene, exercise fanatics have long used the music to help get themselves into the mood for their workouts.
Chinese researchers recently published pre-clinical research demonstrating the use of their protocol for generating stem cell-derived neurons for cell transplantation in Parkinson’s.
The data represents the last step/proof-of-principle stage for taking this procedure into clinical trials (which are ongoing).
In today’s post, we will discuss what cell transplantation is, we will review the new data, and we will consider some of the issues associated with taking this procedure to the clinic.
As we have discussed before, any ‘cure’ for Parkinson’s requires 3 components:
A disease halting mechanism – slowing or stopping the progression of the condition
A neuroprotective agent – a treatment that will protect and support the remaining cells
Some form of cell replacement therapy – introducing new cells to replace the ones that have been lost
Now, the bad new is that there is no ‘silver bullet’ on the horizon that provides all three (for example, there is no neuroprotective agent that also replaces lost cells).
But the good news is that we have a great deal of clinical research being conducted in all three of these areas. This video provides an overview of just some of the many different ways we are approaching all three components:
Recently a research report focused on a cell transplantation (a form of cell replacement therapy) approach for Parkinson’s was published by a group of researchers in China. They have proposed that the results presented in the report justify their efforts to take this approach forward into clinical testing.
This week multiple research groups at the University of Oxford and Boston-based FORMA Therapeutics announced a collaboration to identify, validate and develop deubiquitinating enzyme (DUB) inhibitors for the treatment of neurodegenerative conditions, like Parkinson’s.
But what exactly are DUB inhibitors? And how do they work?
In today’s post, we will answer these questions, look at what the new collaboration involves, and look at what else is happening with DUB inhibitors for Parkinson’s.
Dubstep is a genre of electronic dance music that originated in South London in the late 1990s. Only recently -in the 2010s – has the culture really become more mainstream. And while I have a hard time appreciating the heavy bass music (man, I am becoming a grumpy old man before my time), it is amazing to watch some of the dancers who robotically embody this form of music:
The guy on the right is named Marquese Scott. Sometimes he simply defies the laws of physics.
The title of today’s post is a play on words, because rather than doing ‘Dubstep’ we are going to be discussing how to ‘DUB-stop’.
Researchers in Oxford have recently signed an agreement with a US company to focus resources and attention on a new approach for tackling neurodegenerative conditions, including Parkinson’s.
What they are proposing is a complicated biological dance.
The great ice hockey player Wayne Gretzky once said “A good hockey player plays where the puck is. A great hockey player plays where the puck is going to be” (the original quote actually came from his father, Walter).
At the start of each year, it is a useful practise to layout what is planned for the next 12 months. This can help us better anticipate where ‘the puck’ will be, and allow us to prepare for things further ahead.
2017 was an incredible year for Parkinson’s research, and there is a lot already in place to suggest that 2018 is going to be just as good (if not better).
In this post, we will lay out what we can expect over the next 12 months with regards to the Parkinson’s-related clinical trials research of new therapies.
Charlie Munger (left) and Warren Buffett. Source: Youtube
Many readers will be familiar with the name Warren Buffett.
The charming, folksy “Oracle of Omaha” is one of the wealthiest men in the world. And he is well known for his witticisms about investing, business and life in general.
“We look for three things [in good business leaders]: intelligence, energy, and integrity. If they don’t have the latter, then you should hope they don’t have the first two either. If someone doesn’t have integrity, then you want them to be dumb and lazy”
“Work for an organisation of people you admire, because it will turn you on. I always worry about people who say, ‘I’m going to do this for ten years; and if I really don’t like it very much, then I’ll do something else….’ That’s a little like saving up sex for your old age. Not a very good idea”
“Choosing your heroes is very important. Associate well, marry up and hope you find someone who doesn’t mind marrying down. It was a huge help to me”
Mr Buffett is wise and a very likeable chap.
Few people, however, are familiar with his business partner, Charlie Munger. And Charlie is my favourite of the pair.
At the end of each year, it is a useful practise to review the triumphs (and failures) of the past 12 months. It is an exercise of putting everything into perspective.
2017 has been an incredible year for Parkinson’s research.
And while I appreciate that statements like that will not bring much comfort to those living with the condition, it is still important to consider and appreciate what has been achieved over the last 12 months.
In this post, we will try to provide a summary of the Parkinson’s-related research that has taken place in 2017 (Be warned: this is a VERY long post!)
The number of research reports and clinical trial studies per year since 1817
As everyone in the Parkinson’s community is aware, in 2017 we were observing the 200th anniversary of the first description of the condition by James Parkinson (1817). But what a lot of people fail to appreciate is how little research was actually done on the condition during the first 180 years of that period.
The graphs above highlight the number of Parkinson’s-related research reports published (top graph) and the number of clinical study reports published (bottom graph) during each of the last 200 years (according to the online research search engine Pubmed – as determined by searching for the term “Parkinson’s“).
PLEASE NOTE, however, that of the approximately 97,000 “Parkinson’s“-related research reports published during the last 200 years, just under 74,000 of them have been published in the last 20 years.
That means that 3/4 of all the published research on Parkinson’s has been conducted in just the last 2 decades.
And a huge chunk of that (almost 10% – 7321 publications) has been done in 2017 only.
Structure of tryptophan. Source: Wikipedia
Source: Wikimedia
The Science of Parkinson's 
