Monthly Research Review – August 2021

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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 August 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during August 2021?

In world news:

August 6th – SpaceX stacked the Super Heavy Booster 4 and Star Ship 20 (Click here to read more about this)

 

August 9th – The Intergovernmental Panel on Climate Change releases the first part of its Sixth Assessment Report, which concludes that the effects of human-caused climate change are now “widespread, rapid, and intensifying“.

 

August 13th – Gino Strada passed away – and shame on you if you don’t know who he is

 

August 15th – The 50th anniversary of Nixon closing the “gold window” to foreign countries and ‘temporarily‘ abandoning the Bretton Woods Agreement, removing the gold standard and starting a new age of fiat currencies.

 

August 28th – The world’s northernmost island – a small patch of land measuring 60 x 30 metres – was announced by scientists off the coast of Greenland. The name Qeqertaq Avannarleq is proposed, which means “the northernmost island” (original!).

In the world of Parkinson’s research, a great deal of new research and news was reported:

In August 2021, there were 765 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (8,101 for all of 2021 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 4 pieces of Parkinson’s news

Continue reading “Monthly Research Review – August 2021”

Monthly Research Review – July 2021

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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 July 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during July 2021?

In world news:

July 8th – The global death toll from COVID-19 surpassed 4 million lives (Click here to read more about this).

July 11th — Billionaire Sir Richard Branson flew really high. A new age of “space” tourism… blah, blah, blah.

July 20th Billionaire Jeff Bezos flew really high (yawn)… Seriously, these folks have accumulated vast fortunes and this is how they chose to spend their money?!?!?

July 22nd – Dawn Butler was forced to leave the UK House of Commons by order of the acting Deputy Speaker, after she made comments referring to the Prime Minister Boris Johnson as a liar. Two questions: 1.) Why did her peers not walk out in solidarity with her?  2.) Why did the deputy speaker not point out the obvious (“All politicians are by nature“). Yes, I am a cynic.

July 23rd  – the Tokyo Olympic games began.

July 29th – New Zealand-based Rocket Lab successfully reached orbit (actual space) – the 18th electron rocket to do so.

In the world of Parkinson’s research, a great deal of new research and news was reported:

In July 2021, there were 819 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (7,336 for all of 2021 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

Continue reading “Monthly Research Review – July 2021”

AC Immune acquires assets of AFFiRiS

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Alpha synuclein is considered to be an influential factor in Parkinson’s. It is a protein that accumulates and clumps together inside certain nerve cells in many cases of Parkinson’s.

Recently, clinical trials have attempted to target alpha synuclein that is floating around outside of cells. Some of the strategies focus on an approach called ‘immunotherapy’, which involves boosting the immune system to help remove the toxic form of this protein from the body.

This week, one biotech company – AC Immune – bought the Parkinson’s-associated immunotherapy assets off another biotech company – AFFiRiS – which has been developing a potential vaccine for Parkinson’s.

In today’s post, we will discuss what immunotherapy is, look at how AFFiRiS has been trying to apply it to Parkinson’s, and review what AC-Immune plans to do next.

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AC Immune is a a Switzerland-based biotech company that was foundered in 2003.

They are focused on “improving the lives of patients suffering from Alzheimer’s and other neurodegenerative diseases” (Source).

Their approach has primarily centered around the development of immunotherapy approaches. And this week they made a very interesting announcement.

What is immunotherapy?

Continue reading “AC Immune acquires assets of AFFiRiS”

Farnesol: The farnesylator of PARIS

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A build up of “PARkin Interacting Substrate” (or PARIS) protein has been proposed as one potential mediator of the pathology observed in some cases of Parkinson’s. The accumulation of this protein leads to the inhibition of a key protein called PGC-1α, which is a neuroprotective protein that helps to keep cells alive.

For sometime, researchers have been searching for molecules that can act as inhibitors of PARIS, in the hope that blocking PARIS would allow PGC-1α to act freely. Such an agent could have potential as novel treatment for Parkinson’s.

This week a research report was published that describes one possible PARIS inhibitor. It is called farnesol.

In today’s post, we will look at the biology behind PARIS, review the new report, and discuss what exactly is known about farnesol.

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Pont Royal et Musée d’Orsay. Source: Wikipedia

Paris has a special place in my heart for several reasons.

The main one: I proposed to my wife there on the Pont Royal.

We had planned a day out in London, but once we got down to Waterloo “for lunch at a special restaurant“, I surprised her with two Euro Star tickets and we were off on the train for Paris – just like that (I might look the hardened tough guy on the outside, but deep down I am really just a tragic romantic).

And that night, after “dinner at a special restaurant” shortly before 10pm as we were crossing the middle of the Pont Royal, and a small miracle occurred: the traffic lights stopped traffic in both directions.

Source: Pixels

Seizing our chance moment alone, I dropped to one knee and asked (read: begged).

Now, if she had said ‘no thanks‘, I had a back up plan: Jump over the side of the bridge, float down the Seine some ways, climb out and then join the Foreign Legions the next day as a mute (je suis muet”).

But she didn’t say no (let’s call that the second small miracle) and thankfully for my fragile ego’s sake there wasn’t a lengthy deliberation.

When the traffic lights changed and traffic started to flow again, we received some enthusiastic honks of the klaxons (horns) as I got up and we headed off to alert our parents. It was a really nice moment.

I was recalling this moment, this week when a different type of Paris was being discussed in the news.

What do you mean “a different type of Paris”?

Continue reading “Farnesol: The farnesylator of PARIS”

Monthly Research Review – June 2021

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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 June 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during June 2021?

In world news:

June 3rd – The Juno spacecraft performed its only flyby of Jupiter’s moon Ganymede – the first flyby of the moon by any spacecraft in over 20 years (Click here to read more about this).

June 10th – Researchers from Toshiba’s UK laboratory in Cambridge successfully sent quantum information over 600-kilometer-long optical fibers, creating a new distance record and paving the way for large-scale quantum networks that could be used to exchange information securely between cities and even countries (Click here to read more about this).

June 11th – ‘My God, I’m in a whale’s mouth’: A New England lobsterman named Michael Packard found himself in the mouth of a humpback whale off the coast of Cape Cod. He was spat out half a minute later (Click here to read more about this).

June 23 – The New Zealand Black caps cricket team won the 2019–2021 ICC World Test Championship (Click here to read more about this).

June 29 – The number of vaccinations administered worldwide against the COVID-19 pandemic exceeded 3 billion (a truly remarkable achievement)

In the world of Parkinson’s research, a great deal of new research and news was reported:

In June 2021, there were 1,058 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6,517 for all of 2021 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 4 pieces of Parkinson’s news

Continue reading “Monthly Research Review – June 2021”

The Anavex results

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This week some encouraging clinical trial results were announced by a biotech firm called Anavex Life Sciences.

The company had been testing their lead experimental therapy – a Sigma-1 receptor agonist called ANAVEX2-73 (also known as blarcamesine) – in 132 people with Parkinson’s disease dementia over a 14 week period.

The results are rather encouraging: significantly positive outcomes in both cognitive and motor symptoms.

In today’s post, we will explain what exactly “Sigma-1 receptor agonist” means, discuss what Parkinson’s disease dementia is, and review what we currently know about the results of the trial.

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Source: Pumpingmarvellous

A lot of clinical trials for disease modification in Parkinson’s are focused on targeting well known proteins that are believed to be associated with underlying biology of the condition, such as alpha synuclein, LRRK2, and GBA. We discuss these on a regular basis here on the SoPD.

There are, however, a large number of trials investigating less well known targets.

And this week we received news that one of these clinical trials had some positive results.

Source: Thestreet

The study was conducted by the biotech company Anavex Life Sciences and it involved their lead experimental therapy ANAVEX2-73 (also known as blarcamesine).

ANAVEX2-73 is a Sigma-1 receptor agonist.

What does that mean?

Continue reading “The Anavex results”

EJS-ACT PD

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This week an announcement was made regarding The Edmond J. Safra Accelerating Clinical Treatments for Parkinson’s Disease (EJS-ACT PD) Initiative.

It is hoping to revolutionise the way clinical trials for potentially disease-modifying drugs for Parkinson’s are conducted.

The project is focused on the setting up a multi-arm, multi-stage (MAMS) platform for evaluating new therapies for PD.

In today’s post, we will discuss what MAMS trials involve and the current details of the EJS-ACT PD initiative.

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Source: Motionarray

This week I boarded a train for the first time in 16 months and made my way down to London. It felt a wee bit surreal.

I arrived at Liverpool street station and was immediately shocked by the lack of crowds, the lack of face masks (seriously?!? I’ve had my two jabs as well, but I’m still wearing my mask – you are nuts if you don’t!), and the large number of empty shops. How the world has changed.

In the early morning light, I walked across central London towards St Pancras station – the weather was spectacular and it was an incredible pleasure to stroll through some old stomping grounds.

Source: Parksandgardens

At St Pancras station, I made my way to the enormous Francis Crick institute, where a group of Parkinson’s researchers and advocates were gathering for a really intriguing meeting.

Source: Timeshighereducation

What was the meeting about?

Continue reading “EJS-ACT PD”

G.P.N.M.B

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There is a critical need for good biomarkers in neurodegenerative research.

A biomarker is an objective indicator of a medical state that can be assessed from outside a patient, and can be measured accurately and reproducibly. It could come in the form of a medical imaging application or a biological sample (such as a blood test).

Recent research points towards a particular protein (referred to as GPNMB) that could be a potential biomarker for a specific subtype of Parkinson’s.

In today’s post, we will review some of the research on this topic and consider how a biomarker could potentially be used in Parkinson’s research.

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Source: TED

Back in 2016, some researchers reported something interesting.

They had been investigating cells collected from people with a condition called Gaucher disease (Pronounced: ‘Go-Shay’; don’t ask – we’ll discuss what it is in a moment, just let me get the intro out of the way). Specifically, the scientists were seeking potential biomarkers for Gaucher disease… and they might have found one.

Here is their report:

Title: Elevation of glycoprotein nonmetastatic melanoma protein B in type 1 Gaucher disease patients and mouse models.
Authors: Kramer G, Wegdam W, Donker-Koopman W, Ottenhoff R, Gaspar P, Verhoek M, Nelson J, Gabriel T, Kallemeijn W, Boot RG, Laman JD, Vissers JP, Cox T, Pavlova E, Moran MT, Aerts JM, van Eijk M.
Journal: FEBS Open Bio. 2016 Jul 30;6(9):902-13.
PMID: 27642553                 (This report is OPEN ACCESS if you would like to read it)

In the study, the researchers collected cells from the spleen of an individual with Gaucher disease and looked for proteins in the cells that were higher than normal.

They found glycoprotein non-metastatic melanoma protein B (GPNMB, also known as osteoactivin) was ridiculously high. Off the charts high. They then compared GPNMB levels in blood samples collected from 59 people with Gaucher disease and 20 healthy controls. As you can see in the graph below, GPNMB levels were on average 25‐fold higher in all of the 59 people with Gaucher disease (Note: the Y axis is logarithmic):

Source: PMC

Interestingly, when the individuals with Gaucher disease started the standard treatment for the condition, the levels of GPNMB collectively dropped:

Source: PMC

And this result has been independently validated (Click here to read that report). The second study used a larger cohort of individuals with Gaucher disease (155 patients) and they found a >15-fold elevation of GPNMB in the blood of this group (compared to controls). And again these high levels were reduced when the Gaucher group started treatment:

Source: PMC

A third study found that GPNMB levels in the brains of a mouse model of Gaucher disease correlated with disease severity in the mice, and also reported elevated GPNMB levels in brain samples from patients with Gaucher disease.

All of the research groups concluded that their data supports the potential utility of GPNMB as a biomarker of Gaucher disease.

Great! But what is Gaucher disease and why is this on a website for Parkinson’s research?

Continue reading “G.P.N.M.B”

Monthly Research Review – May 2021

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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 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during May 2021?

In world news:

May 5th – Tech company SpaceX successfully flew and landed their Starship prototype for the first time:

May 9th – The 100th anniversary of the birth of Sophie Scholl (Click here to learn more about her)

 

May 10th – A pan-coronavirus mRNA nanoparticle vaccine with activity against all major SARSCoV2 variants was described in the science journal ‘Nature’, showing potent effect in non-human primates (Click here to read more about this).

May 14th – The China National Space Administration landed its Zhurong rover at Utopia Planitia on Mars, making China the fourth country to land a spacecraft on the planet and the second to land a rover (Click here to read more about this).

May 26th – Oil company Shell became the first company to be legally mandated to align its carbon emissions with the Paris climate accord, following a landmark court ruling in the Netherlands (Click here to read more about this).

In the world of Parkinson’s research, a great deal of new research and news was reported:

In May 2021, there were 911 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5,459 for all of 2021 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

Continue reading “Monthly Research Review – May 2021”

Denali’s Phase I results

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Leucine-rich repeat kinase 2 (or LRRK2) is a large, multi function protein that is associated with Parkinson’s. People with genetic variations in the region of DNA that provides the instructions for making LRRK2 protein have a higher risk of developing the condition.

In many cases of Parkinson’s, LRRK2 can become hyperactive. Researchers and biotech companies have been striving to identify drug-like molecules that can dampen down this hyperactivity in the hope of slowing down the progression of Parkinson’s.

One of the leading biotech firms in this area of research is Denali Therapeutics, and recently the company has provided some updates on their progress.

In today’s post, we will discuss what LRRK2 is, we will look at what Denali have achieved thus far, and we will review what the company has recently announced.

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Source: Denali

A presentation was given at the UBS 2021 Global Healthcare Virtual Conference this week by representatives from Denali Therapeutics.

The slide deck (which can be found here on the company’s website) touched on multiple lines of active research for the company, including their active clinical trial programs:

  • DNL310 (ETV:iduronate-2-sulfatase (IDS) for Hunter syndrome), which has expanded testing in Phase 1/2 based on positive interim data
  • DNL343 (EIF2B activator indicated for ALS), which has had positive interim Phase 1 data, and the company is planning a Phase 1b study in ALS (Click here to read a recent SoPD post on EIF2B activation)
  • DNL788 (RIPK1 inhibitor targeted at ALS, Alzheimer’s, & Multiple Sclerosis … I’m really curious, why not PD?!?), which is in ongoing Phase 1 studies in healthy volunteers (in collaboration with Sanofi)
  • DNL758 (aka SAR443122; another RIPK1 inhibitor targeted at inflammation), currently recruiting participants for a Phase 2 study of lupus & in Phase 1 for COVID-19 lung disease (again in collaboration with Sanofi)

Source: Denali

But of particular interest to us here at SoPD HQ were the slides on their LRRK2 inhibitor clinical trial data.

Founded in 2013 by a group of former Genentech executives, San Francisco-based Denali Therapeutics is a biotech company which is focused on developing novel therapies for people suffering from neurodegenerative diseases.

Ex-Genentechers. Source: Medicalstartups

Although they have product development programs for other condition (such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease), Parkinson’s is definitely one of their primary indications of interest.

The company has been leading the charge in the development of LRRK2 inhibitors as a potential therapeutic class for Parkinson’s and they have recently made some big announcements.

What are LRRK2 inhibitors?

Continue reading “Denali’s Phase I results”