Tagged: Parkinsons

Targeting PDE1 for PD

 

Many novel therapies are currently being clinically tested in Parkinson’s, and this week we heard the results of one clinical trial which provided some very interesting news.

Intra-Cellular Therapies has been testing their drug, ITI-214 – which is a potent and selective phosphodiesterase 1 (PDE1) inhibitor. Inhibitors of PDE1 prevent the breakdown of protein called cyclic nucleotides (cAMP, cGMP).

The results of the Intra-Cellular Therapies clinical trial suggest that in people with Parkinson’s, the drug not only improves symptoms, but also reduces dyskinesias.

In today’s post we will discuss what PDE1 is, how PDE1 inhibitors work, and what the results of the clinical trial suggest.

 


Source: 2018.myana

Every year in October, the American Neurology Association (ANA) gather in one of the major US cities to share research regarding neurological condtions, like Parkinson’s. And while I did not attend the ANA meeting this year, I was keen to hear the results of one particular clinical study.

It was a trial conducted by a company called Intra-Cellular Therapies.

And they were presenting the results of a Phase I/II trial of their experimental drug ITI-214.

What is special about ITI-214?

ITI-214 is a Phosphodiesterase inhibitor.

What is a phosphodiesterase inhibitor?

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Grand times in Grand Rapids

 

During the last week of September, the Van Andel institute and the Cure Parkinson’s Trust held their annual Parkinson’s research meetings in Grand Rapids, Michigan. 

The meetings – the Linked Clinical Trials meeting, Grand Challenges in Parkinson’s, and Rallying to the Challenge – provided an opportunity for members of the Parkinson’s community (both researchers and advocates) to come together, share research/knowledge/experience, and discuss what needs to be done.

I attended the meetings this year for the first time.

In today’s post, I thought I would provide some feedback and share some of my thoughts on the meetings.

 


Jay Van Andel (left) and Rich DeVos. Source: Amwayconnections

The history of Amway is an interesting story.

One of ambition, determination, and a refusal to give up.

It begins with the two founders – Jay Van Andel and Rich DeVos – trying and failing to get seven different businesses off the ground before they eventually founded the multi-level marketing company that we know of as Amway.

Source: Wikipedia

One aspect of the story that many people do not know, however, is that for a decade before he passed away in 2004, Jay Van Andel lived with Parkinson’s.

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Monthly Research Review – September 2018

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 September 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 


So, what happened during September 2018?

In world news:

September 2nd – A fire destroyed the National Museum of Brazil in Rio de Janeiro –  a “catastrophic loss of artifacts”.

Source: HuffPost

September 14th – Hurricane Florence made landfall in Wrightsville Beach (North Carolina), caused extensive damage and flooding throughout in the Carolinas.

Source: WPLG

September 17th – In an effort to study the hidden physical properties of electrons, Japanese researchers built the ‘most powerful magnet on Earth’ – a 1200 Tesla, 3.2 megajoules beast. The experiment was supposed to go off with a bang, but the ‘bang’ was slightly more than expected: it blew the door off the protective chamber holding the experiment!

September 21st – after a three year journey, the first rover of the Japanese Hayabusa2 spacecraft touched down on the surface of the asteroid Ryugu. A truly remarkable achievement.

Source: NYTimes (some amazing images on this link)

September 24th – Two reports were published – one in the journal Nature Medicine and another in the journal New England Journal of Medicine – describing the case of 29-year-old Jered Chinnock (who 5 years ago could not feel or move his body from the chest down) recovering the ability of assisted walking following spinal cord stimulation and intensive physical therapy.

September 28th – A magnitude 7.5 earthquake hit the island of Sulawesi (Indonesia), causing a tsunami and terrible destruction and loss of life.

Source: Australian

 

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

In September 2018, there were 841 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5978 for all of 2018 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

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The ADHD study from Utah

 

This week a new research report was released that got a few readers concerned.

The article published in the journal Neuropsychopharmacology suggested that there may be an association between early onset Parkinson’s and Attention Deficit Hyperactivity Disorder (or ADHD).

In today’s post, we will discuss what ADHD is, look at what the results of the study are proposing, and we will try to calm some nerves by explaining that while the results are very interesting (if they can be replicated and validated in a larger data set), the association only affects a very small number of individuals.

 


o-ADHD-facebook

Source: Huffington Post

It may come as a bit of a surprise, but one of the most popular pages on this website deals with Attention Deficit Hyperactivity Disorder (or ADHD – click here to read that post).

I am not sure why this is the case.

At the time of writing that particular post, there was very little in the way of any associations between Parkinson’s and ADHD. But this week the number of views for that ADHD post went through the roof.

This increase in activity probably had less to do with my amazing prose and more to do with the release of this research report:

Title: Increased risk of diseases of the basal ganglia and cerebellum in patients with a history of Attention-Deficit/Hyperactivity Disorder
Authors: Curtin K, Fleckenstein AE, Keeshin BR, Yurgelun-Todd DA, Renshaw PF, Smith KR, Hanson GR.
Journal: Neuropsychopharmacology. 2018 Sep 12.
PMID: 30209407

The release of this report has been led to all kinds of media headlines (Click here and here for examples), and some panicked emails to SoPD HQ from concerned readers (particularly parents).

For those who don’t have time to read on, here is the short version of what today’s post is going to say: the results of the study are interesting, but the observed association only affects a very small number of individuals. And until the results are replicated and validated in a much larger study, there is little reason to panic.

And now for the ridiculously long version of this post – let’s start with the obvious first question:

What is ADHD?

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Monthly Research Review – August 2018

 

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 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 

 


So, what happened during August 2018?

In world news:

August 1 – American technology company became the world’s first public company to achieve a market capitalization of US$1 trillion.

August 12th – NASA launched the unmanned ‘Parker Solar Probe’ which will study the Sun (up close and personal)

August 16th – Singer, song writer and pianist Aretha Louise Franklin passed away (sad day)

August 31st – Joe Giaglia, director of California Skateparks, who had previously made a x12.5 scale replica of a skate board finally got it certified by Guinness World Records as the largest in the world.

Seriously, it measures 35 feet, 7 inches long (10.8 meters)!

 

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

In August 2018, there were 679 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5372 for all of 2018 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

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On the hunt for biomarkers

 

The monitoring and assessment of the symptoms/features of Parkinson’s is a big deal in the research community at the moment.

There is currently a mad hunt for ‘biomarkers’ – reliably measurable physical characteristics – that could help not only with the assessment of individuals living with the condition, but could also aid in the running of clinical trials by providing additional measures of efficacy/benefit.

Recently an interesting perspective was written by some of the leading researchers in this field.

In today’s post, we review what the perspective outlined, and we will discuss other aspects of the biomarker research that need to be considered by the wider Parkinson’s community.

 


Perspective. Source: Huffingtonpost

Scientific journals will often invite the research leaders in a particular field of investigation to write a brief journal article that deals with unique view of a common problem.

Articles of this nature are called ‘Perspectives‘.

And recently a very interesting perspective was published in the journal Science on the topic of biomarkers for Parkinson’s.

Title: Finding useful biomarkers for Parkinson’s disease
Authors: Chen-Plotkin AS, Albin R,….a lot of additional authors…, Zhang J
Journal: Science Translational Medicine, 15 Aug 2018, 10 (454), eaam6003.
PMID: N/A

This perspective included a rather long list of a ‘who’s-who’ of Parkinson’s researchers – both academic and industry. Even members of the Michael J Fox Foundation and Verily/Google Life Sciences were included.

The perspective sought to highlight ‘the “ecosystem” of shared biofluid sample biorepositories and data sets will focus biomarker efforts in Parkinson’s‘. It is a very enlightening read, one that begs for reader responses. But sadly the article is behind a ‘pay wall’, and so many in the Parkinson’s community won’t be able to provide any thoughts or feedback.

Shame.

But not to worry, we can discuss the matter here. And the best place to start that discussion is with the obvious first question:

What is a biomarker?

A biomarker is an objectively measurable physical characteristic associated with a condition. It is a biological component of a condition that correlates with that condition in some way. For example, the DaTscan brain imaging technique provides a ‘biomarker’ for Parkinson’s by measuring the amount of dopamine re-absorption in the brain. By labelling the dopamine neurons with a radioactive marker, we can quantify the levels of dopamine activity in a person.

An example of a DaTscan. Source: Cedars-sinai 

What did the perspective say about biomarkers for Parkinson’s?

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Monthly Research Review – July 2018

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 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 


So, what happened during July 2018?

In world news:

July 1-31st – Best summer weather ever in the UK (personal opinion based on 12 years experience)

July 7 – Fifty three couples lined up for the 23rd Annual Wife Carrying Championship (?!?). The hour-long race in the small Finnish town of Sonkajarviwas was won by a Lithuanian couple (congrats to Vytautas Kirkliauskas and his wife Neringa Kirkliauskiene). The image below is from one of the UK contests (looks like pretty serious stuff, huh?).

July 10 – Twelve boys and their football coach are successfully rescued from the flooded Tham Luang Nang Non cave in Thailand, following a 17-day ordeal that gained worldwide attention.

July 25 – Scientists report the discovery of a subglacial lake on Mars, 1.5 km below the southern polar ice cap. The lake, extending out about 20 km, is the first known body of water on the planet.

July 27 – The longest total lunar eclipse of the 21st century occurred, and Mars makes its closest approach to Earth since 2003.

 

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

In July 2018, there were 645 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4751 for all of 2018 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

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Voyager Therapeutics update

This week a biotech company called Voyager Therapeutics provided an update regarding a gene therapy approach for people with severe Parkinson’s.

Gene therapy is an experimental therapeutic approach that involves inserting new DNA into cells using a virus. The introduced DNA can help a cell to produce proteins that it usually wouldn’t  produce, and this can help to alleviate the motor features of Parkinson’s.

In today’s post we will discuss what gene therapy is, what Voyager Therapeutics is trying to do, and outline what their update reported.


There are 4 phases to the clinical trial process of testing new treatment for use in humans:

  • Phase I determines if a treatment is safe in humans (this is conducted in an ‘open label’ manner)
  • Phase II ‘double blindly’ assesses in a small cohort of subjects if the treatment is effective
  • Phase III involves randomly and blindly testing the treatment in a very large cohort of patients
  • Phase IV (often called Post Marketing Surveillance Trials) are studies conducted after the treatment has been approved for clinical use

(‘Open label’ refers to both the investigator and the participants in a study knowing what treatment is being administered; while ‘double blind’ testing refers to studies in which the participants and the investigators do not know whether the participant is receiving the active treatment or an inert control treatment until the end of the study).

Based on the successful completion of their Phase I clinical trials for their gene therapy treatment called VY-AADC (Click here to read more about this), Boston-based biotech firm Voyager Therapeutics approached the US Food and Drug Administration (FDA) with the goal of shifting their clinical trial programme into Phase II testing.

What is gene therapy?

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TRIMming aggregates

 

Novel methods for treating neurodegenerative conditions are being proposed on a weekly (sometimes daily) basis.

Recently researchers from the University of Cambridge have presented an intriguing new method of removing proteins from inside of cells which involves small proteins called antibodies.

Antibodies are an important part of the immune systems response to infection. But their function usually only applies to objects floating around outside of cells. 

In today’s post, we will look at what antibodies are, explain how this new system works, and discuss some of the issues we face with taking this new technique forward.


A brain cell from a person with Alzheimer’s. The red tangles in the yellow cell body are toxic misfolded “TAU” proteins next to the cell’s green nucleus. Source: NPR

Here at the SoPD, we often talk about the clustering (or aggregation) of proteins.

Densely packed aggregates of a protein are a common feature of many neurodegenerative conditions, including Parkinson’s.

In fact, the aggregation of a protein called alpha synuclein are one of the cardinal features of the Parkinsonian brain.

Lewy_neurites_alpha_synuclein

Aggregated alpha synuclein protein in the Parkinsonian brain (stained in brown). Source: Wikimedia

Researchers have long been devising new ways of trying to reduce the amount of alpha synuclein collecting in the brain cells of people with Parkinson’s.

In most cases, their efforts have focused on utilising the cell’s own waste disposal systems.

How do cells dispose of waste?

There are two major pathways by which the cells in your body degrade and remove rubbish:

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Wanted: EEF2K inhibitors

Nuclear factor erythroid 2–related factor 2 (or NRF2) is a protein in each of your cells that plays a major role in regulating resistance to stress. As a result of this function, NRF2 is also the target of a lot of research focused on neuroprotection.

A group of researchers from the University of British Columbia have recently published interesting findings that point towards to a biological pathway that could help us to better harness the beneficial effects of NRF2 in Parkinson’s.

In today’s post, we will discuss what NRF2 is, what the new research suggests, and how we could potentially make use of this new information.


GettyImages-548553969-56a134395f9b58b7d0bd00df

Rusting iron. Source: Thoughtco

In his book ‘A Red Herring Without Mustard‘, author Alan Bradley wrote:

Oxidation nibbles more slowly – more delicately, like a tortoise – at the world around us, without a flame, we call it rust and we sometimes scarcely notice as it goes about its business consuming everything from hairpins to whole civilizations

And he was right on the money.

Oxidation is the loss of electrons from a molecule, which in turn destabilises that particular molecule. It is a process that is going on all around us – even within us.

Iron rusting is the example that is usually used to explain oxidation. Rust is the oxidation of iron – in the presence of oxygen and water, iron molecules will lose electrons over time. And given enough time, this results in the complete break down of objects made of iron.

The combustion process of fire is another example, albeit a very rapid form of oxidation.

Oxidation is one half of a process called Redox – the other half being reduction (which involves the gaining of electrons).

The redox process. Source: Academic

Here is a video that explains the redox process:

Now it is important to understand, that oxidation also occurs in biology.

Molecules in your body go through the same process of losing electrons and becoming unstable. This chemical reaction leads to the production of what we call free radicals, which can then go on to damage cells.

What is a free radical?

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