Tagged: Parkinson’s
Monthly Research Review – May 2020
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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 2020. The post is divided into seven parts based on the type of research:
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So, what happened during May 2020?
In world news:
May 11th – In two studies published in Nature, and Nature Ecology and Evolution, scientists describe hominin remains and artefacts excavated from the Bacho Kiro Cave (in Bulgaria) that indicate early humans were present in Europe around 46,000 years ago – suggesting the species shared the continent with Neanderthals for longer than previously thought.
May 18th – A Maryland restaurant preparing to reopen amid the ongoing COVID-19 pandemic unveiled its fleet of wheeled bumper tables designed to enforce social distancing:
May 27th – South Korean schools reopened as the country began easing COVID-19-associated lockdown restrictions.
May 29th – South Korea re-closed 200 schools as new cases of COVID-19 spike to 79, the highest daily figure in two months.
May 30th – The age of commercial human spaceflight officially began
In the world of Parkinson’s research, a great deal of new research and news was reported:
In May 2020, there were 782 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4565 for all of 2020 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 6 pieces of Parkinson’s news
Oleh Hornykiewicz (1926-2020)
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# # # # This week it was announced that Oleh Hornykiewicz had passed away. I appreciate that most readers will not know who he is, but understand that his contribution to Parkinson’s research was important. Not only was he instrumental in the discovery that dopamine is significantly reduced in the Parkinsonian brain, but he also demonstrated that levodopa treatment can help restore function. In today’s post, we remember Oleh Hornykiewicz. # # # # |
It was sad to hear of the passing away of Oleh Hornykiewicz this week.
Most readers will have little clue as to who he was, but he played a very important role in the development of the Parkinson’s treatment we know of as levodopa therapy.
Very early in the 20th century, a chemical called dopamine was discovered, but no one really knew anything about it until a young Swedish research named Arvid Carlsson started to play with it.
Prof Arvid Carlsson. Source: Alchetron
In 1957, Carlsson discovered that when he injected a drug called reserpine into the brains of rabbits, the animals exhibited limited ability to move. He found that reserpine depleted levels of dopamine in the brains of the rabbits. He also discovered that by injecting the dopamine precursor – levodopa (more on this below) – into those same animals, he was able to rescue their motor ability. Importantly, he found that the precursor (called 5-hydroxytryptophan) to another chemical called serotonin, it was not capable of reversing the reduction in motor ability, indicating that the effect was specific to levodopa and dopamine.
He published this amazing result in the prestigeous scientific journal ‘Nature’:
Title: 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists.
Authors: Carlsson A, Lindqvist M, Magnusson T.
Journal: Nature. 1957 Nov 30;180(4596):1200. No abstract available.
PMID: 13483658 (the article on the Nature website – access required)
This was a fantastic discovery.
But what to do with it?
And that is where an Austrian researcher named Oleh Hornykiewicz becomes part of the story.
PDCORE
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# # # # Assessing the progression of Parkinson’s is a very difficult task, but accurately doing so is critical to our ability to evaluate the disease modifying potential of new therapies. The clinical measures currently used in clinical trials have been developed using large longitudinal studies that assessed individuals over long periods of time. But the utility of these tools have been called into question as we try to measure subtle changes in progression. Using post-hoc (after the fact) analysis of recent clinical trial data, however, researchers have recently proposed a new method of assessment that they call “The Parkinson’s Disease Comprehensive Response” (or PDCORE). In today’s post, we will discuss what PDCORE is and how it was identified. # # # # |
Joe Brown. Source: theBMC
I am not a climber (in fact, despite being rather tall, I am not very good at heights).
I certainly do not understand the mentality of people that need to climb mountains just to reach the top, particularly if they are simply following the same route as every other person climbing the same peak. And images of traffic jams in the “death zone” (above 8,000 meters) of Everest completely befuddle me.
Waiting for bragging rights?!? Source: NYTimes
So on the 15th April of this year when I heard about the passing of a climber named Joe Brown, I thought nothing of it… until that is, I read his story.
And more importantly his philosophy.
You see, Joe was deeply passionate about climbing and was considered one of the best by many. But for Joe it was never about getting to the top of the mountain, it was always about finding a new route up a mountain or a new way of doing something that compelled him.
Joe Brown. Source: Economist
This is a mentality I can appreciate.
It is also an idea that the Parkinson’s research community needs to embrace. If we are simply doing things because they are the way we have always done things, something is wrong.
Like Joe Brown, we need to be exploring new routes.
Which is why in today’s post we will be discussing PDCORE.
What is PDCORE?
Skin in the game
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# # # # This week we received news of a case study involving a cell transplantation procedure that was performed during 2017/2018 on an American gentleman with Parkinson’s. The operation (conducted in in Boston, USA) involved isolating skins cells from the individual who under went the surgery, then converting those cells into stem cells which were further encouraged to become dopamine neurons before being transplanted into his brain. Although this is a single subject study (no control group), the result suggests that 2 years on the procedure is safe and well tolerated. In today’s post, we will discuss the background of this research, review the published results, and explore other aspects of this story. # # # # |
Source: Medium
On the 12th May, a story was posted on the online news site, STATnews.
I like STATnews (not an endorsement, just me sharing). They have lots of interesting stories covering a wide range of health and biotech topics.
But the story on the 12th May was different.
It focused on clinical study that involved just one participant – a gentleman from Southern California who was afflicated by Parkinson’s. He underwent a procedure called cell transplantation (Click here to read the STATnews story).
What is cell transplantation?
MAMS the word
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# # # # The way that clinical trials are conducted doesn’t make much sense. They take too long and a lot of resources to set up, they take a long time to be conducted, and we have to wait until they are finished before we get the results. And then on top of that we need to repeat the whole process everytime we want to make any further progress. More efficient and adaptive models of clinical trials have been used in other medical conditions, and, thankfully, researchers are now asking if these could also be applied to Parkinson’s In today’s post, we will discuss a recent review that explores the use of Multi-Arm Multi-Stage trial design, and asks how they could be applied to neurodegenerative conditions, like PD. # # # # |
Source: Mumstheword
“Mum’s the word” is a popular English idiom. It refers to not talking about a particular topic.
But where on Earth did the phrase come from?!?
In writing these blog posts, I like to try and devise clever (some might fairly say silly) titles to grab the attention of the reader. But these efforts often lead to distracting deviations of curiosity about the origins of certain quotes or titles.
“Mum’s the word” is a good example. I have used the phrase a lot in the past, but never questioned its origins. Until today that is.
Source: Biblio
The first time it appears in print is in A Walk Around London and Westminster – The Works of Mr. Thomas Brown, written in 1720 (“But Mum’s the Word – for who would speak their Mind among Tarrs and Commissioners“).
The phase, however, derives from the Latin “mimus” meaning “silent actor”, which evolved into ‘mummer’ in Old English. “Mummers” were artists who performed dances, games or plays in complete silence. Curiously this tradition is still maintained in the form of the Mummers Parade, which is held each New Year’s Day in Philadelphia:
Philadelphia Mummers Parade – doesn’t look very silent. Source: ABC
The word ‘mum’ in this context first appeared in print in William Langland’s Middle English poem “Piers Plowman” from the 1370s, and even Shakespeare has used the word ‘mum’ in his Henry VI (Part 2, Act 1, Scene 2: “Seal up your lips and give no words but mum”).
Interesting. But what has this got to do with Parkinson’s?
Nothing.
Like I said, it was just a silly attempt at making a cute title for this blog post.
And now, to business: Today we are going to discuss a new review exploring Multi-Arm Multi-Stage clinical trials and their potential use in Parkinson’s.
What does Multi-Arm Multi-Stage mean?
Getting a GRP on dyskinesias
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# # # # Dyskinesias are involuntary muscle movements associated with long-term use of levodopa therapy (use of levodopa is not a certainty for developing dyskinesias, but there is an association). A better understanding of the underlying biology of dyskinesias is required in order to alleviate this condition for those affected by it. This week researchers reported that a single protein – called RasGRP1 – plays a central role in the development of dykinesias, raising hope that agents targeting this protein could identified and provide better quality of life of sufferers. In today’s post, we will discuss what dyskinesias are and review the new research. # # # # |
Few people outside of the biomedical sciences may have heard of the Scripps Research Institute, but it is the largest private, not-for-profit medical research facility in the United States and among the largest in the world. It is headquartered in La Jolla, California but it has a sister facility in Jupiter, Florida.
Nice spot to do research. Source: Scripps
Collectively, “The Scripps” has 250 laboratories, which employs over 2,400 scientists, technicians, graduate students, and administrative staff.
It was founded in 1924 by journalist/philanthropist Ellen Browning Scripps.
Ellen Browning Scripps. Source: Lajollalight
The Scripps covers a wide variety of area in biomedical research, but this week a group of researcher led by scientists at the Florida Scripps institute published an interesting report on Parkinson’s:
Title: RasGRP1 is a causal factor in the development of l-DOPA–induced dyskinesia in Parkinson’s disease
Authors: Eshraghi M, Ramírez-Jarquín1 UM, Shahani1 N, Nuzzo T, De Rosa A, Swarnkar S, Galli N, Rivera O, Tsaprailis G, Scharager-Tapia C, Crynen G, Li Q, Thiolat ML, Bezard E, Usiello A, Subramaniam S
Journal: Science Advances, May 2020, 6, 18, eaaz7001
PMID: 32426479 (This report is OPEN ACCESS if you would like to read it)
In this study, the researchers were interested in proteins that could be playing a major role in the development of dyskinesias.
What are dyskinesias?
Putting the PARKIN back into Parkinson’s
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# Genetic variations in a region of our DNA called PARKIN is associated with an increased risk of developing Parkinson’s – particularly young-onset PD (diagnosed before the age of 40yrs). This area of DNA provides the instructions for making a protein (also referred to as PARKIN), which plays a number of important roles inside of cells. Recently, a South Korean biotech company called Cellivery has published research on an experimental therapeutic agent that easily penetrates both the brain and cells within, delivering PARKIN protein to the cells that need it. In today’s post, we will discuss what PARKIN does, review the new research report, and explore what could happen next. # |
Source: Quanta
Here on the SoPD we often talk about research regarding the prominent Parkinson’s associated proteins, think of alpha synuclein, LRRK2 and GBA. And they are of interest as there is a great deal of activity now at the clinical level exploring agents targetting these proteins.
But there are a number of interesting therapeutics being developed that are exploring some of the other Parkinson’s-associated proteins.
A good example was published this week:
Title: Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein
Authors: Chung E, Choi Y, Park J, Nah W, Park J, Jung Y, Lee J, Lee H, Park S, Hwang S, Kim S, Lee J, Min D, Jo J, Kang S, Jung M, Lee PH, Ruley HE & Jo D
Journal: Science Advances, 29 Apr 2020:6, 18, eaba1193
PMID: N/A
In this study, South Korean researchers demonstrated that a brain penetrating compound (including the PARKIN protein) can rescue numerous models of Parkinson’s.
Hang on a second: What is PARKIN?
Monthly Research Review – April 2020
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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 2020. The post is divided into seven parts based on the type of research:
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So, what happened during April 2020?
In world news:
April 2nd – Billionaire Amazon founder Jeff Bezos donated $100 million to Feeding America, a nonprofit that helps food banks feed families in need (Source).
April 6th – In March, billionaire Jack Ma donated 1.1 million COVID-19 testing kits, 6 million masks and 60,000 medical use protective suits/face shields to Africa. On this date, he sent a second shipment (including 500 ventilators – source).
April 7th – Billionaire founder of Twitter, Jack Dorsey, announced he was donating $1billion (28% of his net wealth) to help fund COVID-19 relief (source).
(For more on how billionaires are supporting the COVID-19 effort – click here)
April 20th – Oil prices reached a record low (falling into negative values) due to the ongoing coronavirus pandemic and the Russia–Saudi Arabia oil price war
April 30th – Captain Tom Moore – a war veteran who has raised over £32.79 million for the NHS by completing 100 laps (25m/27yd) of his garden in 10 days – celebrated his 100th birthday
In the world of Parkinson’s research, a great deal of new research and news was reported:
In April 2020, there were 976 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (3340 for all of 2020 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 6 pieces of Parkinson’s news
The Pasadena study announcement
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# # # # This week the outcome of an ongoing Parkinson’s clinical trial was announced. Data collected during Part 1 of the ongoing Phase 2 PASADENA alpha synuclein immunotherapy study for Parkinson’s apparently suggests that the treatment – called prasinezumab – has not achieved it’s primary endpoint (the pre-determined measure of whether the agent has an effect in slowing Parkinson’s progression – in this case the UPDRS clinical rating scale). But, intriguingly, the announcement did suggest ‘signals of efficacy‘ in secondary and exploratory measures. In today’s post, we will discuss what immunotherapy is, what we know about the PASADENA study, and why no one should be over reacting to this announcement. # # # # |
At 7am on Wednesday, April 22nd, 2020, the pharmaceutical company Roche published its sales results for the 1st Quarter. This was just prior to the opening of the Swiss Stock Exchange. The financial report looked very good, particularly considering the current COVID-19 economic climate.
There was, however, one sentence on page 133 of the results that grabbed some attention:
Source: Roche
For those of you (like myself) who struggle with fine print, the sentence reads:
“Study did not meet its primary objective, but showed signals of efficacy“
This was how the pharmaceutical giant announced the top line result of the ongoing Phase II PASADENA study evaluating the immunotherapy treatment prasinezumab in recently diagnosed individuals with Parkinson’s (listed on the Clinicaltrials.gov as NCT03100149).
At the time of publishing this SoPD post, Roche are yet to provide any further information (press release, announcement, memo, tweet, etc) regarding the results of the study.
Thankfully, a smaller biotech firm called Prothena – which is also involved in the development of the agent being tested in the Pasadena study – has kindly provided a few more details regarding these results.
I usually don’t like discussing clinical trial results on the SoPD until the final report is published, but in this circumstance I will make an exception.
In today’s post we will discuss what details have been shared in the Prothena press release regarding the Prasinezumab clinical trial in Parkinson’s (Click here to read the press release).
What is Prasinezumab?
CasRx Reprogramming
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# # # # Parkinson’s is a neurodegenerative condition – this means that certain cells in the brain are being lost. Restorative therapies are those focused on replacing the lost cells in the hope that the new cells will be able to take up the lost function. Tremendous efforts are being made in cell transplantation programs for Parkinson’s. But this month scientists have published a new research report proposing a novel method of changing the fate of cells already in the brain (removing the need to introduce new cells). Their approach involves new technology and remarkably only requires the manipulation of a single protein. In today’s post, we will explore the growing world of in vivo reprogramming, review the new research report, and discuss where in vivo reprogramming could go next. # # # # |
Changing cell fates. Source: MDPI
In vivo reprogramming of cells is a red hot topic in restorative research at the moment. The ability to change the fate of mature cells inside of an organism represents a ‘holy grail’-like goal for regenerative medicine.
Rather than transplanting ‘foreign’/external cells into the body (and having to deal with an immune system response), in vivo cellular reprogramming offers the possibility of simply changing the fate of a cell that is already present inside the body. And there are a lot of research groups around the world now exploring various methods of achieving this goal.
We have discussed the background research associated with in vivo cellular reprogramming for Parkinson’s in a previous SoPD post (Click here to read that post).
In today’s post, we are going to discuss a new research report that was published this month on this topic:
Title: Glia-to-Neuron Conversion by CRISPR-CasRx Alleviates Symptoms of Neurological Disease in Mice.
Authors: Zhou H, Su J, Hu X, Zhou C, Li H, Chen Z, Xiao Q, Wang B, Wu W, Sun Y, Zhou Y, Tang C, Liu F, Wang L, Feng C, Liu M, Li S, Zhang Y, Xu H, Yao H, Shi L, Yang H.
Journal: Cell. 2020 Apr 1. pii: S0092-8674(20)30286-5. [Epub ahead of print]
PMID: 32272060
In this study, the researchers used a new technology (called CRISPR-CasRx) to reduce levels of a single protein, and the reduction of this protein appears to have aided the conversion of cells in the brains of mice to become dopamine neurons – the population of cells that are severely affected in Parkinson’s.
What is CRISPR-CasRx?
