Monthly Research Review – October 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 October 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 October 2018?

In world news:

1st October – The Nobel Prize in Physiology or Medicine is awarded to James P. Allison and Tasuku Honjo for their discoveries in cancer therapy (Click here for the press release).

3rd October – The Nobel Prize in Chemistry is awarded to George P. Smith, Frances Arnold, and Greg Winter for taking control of evolution and designing molecules used it for purposes that bring the greatest benefit to humankind (Click here to read the press release).

8th October – The 27th Human Tower Competition finished in Tarragona, Spain. ‘Castells’ were declared by Unesco one of the Masterpieces of the Oral and Intangible Heritage of Humanity in 2010. Look at the passion of these crazy Catalonians (seriously, take a moment and watch this video):

 

 

 

 

 

(Click here for another example – and turn the sound up to listen to the excitement in the commentator’s voice)

18th October – The auction house Christie’s announced that ‘Portrait of Edmond Belamy’ a painting generated entirely by artificial intelligence, will be sold at auction

(Yeah, I don’t understand art either)

30th October – NASA’s Parker Solar Probe spacecraft flew closer to the Sun than any other human made object, passing within 42.7 million km (26.6 million miles) from the Sun’s surface.

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

In October 2018, there were 647 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (6530 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 6 pieces of Parkinson’s news

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Gene therapy: VY-AADC01 vs AXO-Lenti-PD

 

Future generations may treat conditions like Parkinson’s with DNA rather than drugs. By manipulating the DNA within a given cell, researchers can cause that cell to generate proteins that they usually do not produce.

This technique is called gene therapy, and it is currently being clinically tested in people with Parkinson’s.

Recently, one biotech firm (Voyager Therapeutics) has provided new data on an ongoing clinical trial and another company (Axovant Sciences) has announced the initiation of a clinical study.

In today’s post, we will discuss what gene therapy is, evaluate what the first company has achieved, and compare it with the clinical trial that is just starting.

 


Source: 2018.myana

At the annual American Neurology Association (ANA) meeting this year, we got an update on an ongoing clinical trial for Parkinson’s being conducted by a company called Voyager Therapeutics.

The biotech firm presented data at the meeting regarding their gene therapy approach for Parkinson’s.

What is gene therapy?

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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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A Lewy body condition?

 

Lewy bodies are densely packed, circular clusters of protein that have traditionally been considered a characteristic feature of the Parkinsonian brain. Recently, however, evidence has been accumulating which calls into question this ‘defining feature’ of the condition.

The presence Lewy bodies in some cases of other neurological conditions (such as Alzheimer’s), and their complete absence in some cases of Parkinson’s, are leading many researchers to question their pivotal role in PD.

In today’s post, we will look at a new research report of Parkinson’s post mortem cases studies which present no Lewy bodies, and we will disucss what this might mean for our understanding of Parkinson’s and the future treatment of the condition.

 


Neuropathologists conducting a gross examination of a brain. Source: NBC

At present, a definitive diagnosis of Parkinson’s can only be made at the postmortem stage with an examination of the brain. Until that moment, all cases of Parkinson’s are ‘suspected’. When a neuropathologist makes an examination of the brain of a person who passed away with the clinical features of Parkinson’s, there are two characteristic hallmarks that they will be looking for in order to provide a final diagnosis of the condition:

1.  The loss of specific populations of cells in the brain, such as the dopamine producing neurons in a region called the substantia nigra, which lies in an area called the midbrain (at the base of the brain/top of the brain stem). As the name suggests, the substantia nigra region is visible due to the production of a ‘substance dark’ molecule called neuromelanin in the dopamine neurons. And as you can see in the image below, the Parkinsonian brain has less dark pigmented cells in the substantia nigra region of the midbrain.

The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinsonian brain (right). Source:Memorangapp

2.  Dense, circular clusters (or aggregates) of protein within cells, which are called Lewy bodies.

shutterstock_227273575A cartoon of a neuron, with the Lewy body indicated within the cell body. Source: Alzheimer’s news

A Lewy body is referred to as a cellular inclusion, as they are almost always found inside the cell body. They generally measure between 5–25 microns in diameter (5 microns is 0.005 mm) and thus they are tiny. But when compared to the neuron within which they reside they are rather large (neurons usually measures 40-100 microns in diameter).

A photo of a Lewy body inside of a neuron. Source: Neuropathology-web

Do all Parkinson’s brains have Lewy bodies?

This is a really interesting question. Welcome to the topic of this post.

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When you stop going native

 

Alpha synuclein is a protein that is closely associated with Parkinson’s. But exactly if and how it is connected to the neurodegenerative process underlying the condition, remains unclear. 

Last week researchers reported that removing a particular form of alpha synuclein in mice results in a very early onset appearance of characteristics that closely resemble the features of Parkinson’s that we observe in humans. This finding has caused some excitement in the research community, as not only does this tell us more about the alpha synuclein protein, but it may also provide us with a useful, more disease-relevant mouse model for testing therapies.

In today’s post, we will discuss what alpha synuclein is, explain which form of the protein was disrupted in this mouse model, review the results of the new study, and look at how tetramer stablising drugs could be a new area of PD therapeutics.

 


The 337 metre (1,106 ft) long USS Gerald R. Ford. Source: Wikipedia

Imagine you and I are standing in front of the world’s largest aircraft carrier, the USS Gerald R. Ford.

It is a VAST warship – measuring in at 337 metres (1,106 ft) in length, 76 metres (250 feet) in height – and it is a wonder of engineering composed of over a billion individual components.

And as we are standing there, gazing up at this amazing machine, I turn to you and put a nut & bolt into the palm of your hand.

A nut and bolt. Source: Atechleader

You look down at it for a moment, then turn to me, puzzled.

And that is when I say: “I would like you to find (without aid/instructions) where on this ship versions of this particular type of nut and bolt live, and try to determine exactly what functions they have“.

Where would you even start?

What tools would you use for the job? Considering the size and complexity of the vessel, would you simply give up before even starting?

It sounds like a ridiculously daunting task, but this is in effect what neurobiologists are trying to do with their study of the  brain. They start with a protein – one of the functional pieces of machinery inside each cell of our body – and then try to determine where in the brain it lives (the easy part) and what it does exactly (the REALLY hard part – most proteins have multiple functions and different configurations).

A good example of this is the Parkinson’s-associated protein alpha synuclein:

 

Alpha synuclein. Source: Wikipedia

Alpha synuclein is one of the most abundant proteins in our brains – making up about 1% of all the proteins floating around in each neuron in your head – and it is a very well studied protein (with over 9700 research reports listed on the Pubmed search engine with the key words ‘alpha synuclein’).

But here’s the thing: we are not entirely clear on what alpha synuclein actually does inside the cell. 

Que? 

In fact, biologists are not even sure about what the ‘native’ form of alpha synuclein is!

What do you mean?

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Monitoring Parkinson’s: Doctor, my glasses are listening to us

 

An important aspect of developing new potentially ‘curative’ treatments for Parkinson’s is our ability to accurately test and evaluate them.

Current methods of assessing Parkinson’s are basic at best (UPDRS and brain imaging), and if we do not improve our ability to measure Parkinson’s, many of those novel treatments will fail the clinical trial process and forever remain just “potentially” curative.

Glasses are a wearable device that the majority of us take for granted. But two technology companies have announced that they are partnering up to focus their combined efforts on making a pair of glasses that could help improve the lives of people with Parkinson’s. 

One company focuses on tracking facial expressions, while the other analyses audio. 

In today’s post, we will look at how these technologies could be applied to Parkinson’s, and discuss what the companies have planned.

 


Looking good. Source: 1zoom

An interesting fact:

Approximately 60% of western populations wear glasses, contact lenses or use some other reading/visual aid (Source). And as we age, this percentage only increases – with the over 75 year olds representing a solid collection within the bespectacled crowd (see graph below).

More women than men wear glasses. Source: CBS

I am in the majority.

But mostly for aesthetic reasons (they make me look smarter than I actually am).

Ok, but what does this have to do with Parkinson’s?

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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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The Bill and Melinda burden study

 

Determining exactly how many individuals there are in the world that are affected by Parkinson’s is a difficult task. Previously, a lot of ‘gues-stimation’ has been used in these quantitative efforts. But a clearer idea of the geographical, national and regional spread of Parkinson’s burden, could provide us with very useful information to help better understand the condition.

The Global Burden Disease Collaborators conducted a world-wide assessment of Parkinson’s burden in 2016, and this week the results of their study were published. The findings make for interesting reading. 

In today’s post, we will review the results and discuss what they mean for the Parkinson’s community.

 


Source: Nationalgeographic

This is one of those classic ‘boy meets girl’ stories… but with a ‘saves the world’-kind of twist to it.

Having just graduated from Duke University (with a degree in computer science and economics) in the summer of 1986, Melinda Ann French began working as an intern for IBM. Having learnt to program (in Basic) on Apple II computers during her teens, she was interested in a future career in the developing world of computer technology.

She eventually scored a job with a new company called Microsoft, and for the next 6 years she climbed the corporate ladder, from a software marketing position to general manager of information products (such as Microsoft Bob, Expedia, and Encarta).

Melinda met William (Bill) Henry Gates III four months after starting her job at Microsoft – they happened to sit next to each other at a trade-fair dinner in New York. But several months would pass by before Bill actually asked her out on a date.

They were married in Hawaii on New Years day 1994.

In 2000, the couple launched the Bill and Melinda Gates Foundation – which has gone on to become one of the largest private foundations in the world with US$50+ billion in assets.

Excuse me, this is all very interesting, but what does it have to do 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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Better call Sal(-butamol)?

 

In 2017, a research report suggested that people taking the asthma treatment Salbutamol had a lower risk of developing Parkinson’s. In addition, that same study suggested that another medication called Propranolol – which is used for hypertension/high blood pressure – increased ones risk of developing Parkinson’s. 

Both drugs work via a molecule called the Beta2 adrenoreceptor. The study caused a lot of excitement, and clinical studies were even proposed.

Now, however, new research suggests that these associations may not actually exist and those clinical trial plans will be need to be put on standby.

In today’s post we will discuss what the Betaadrenoreceptor is, how these two drugs (Salbutamol and Propranolol) affect it, and look at what the new results suggest.

 


Saul Goodman. Source: Amc

There is a popular show on Netflix called ‘Better call Saul’ (the title of this post is a play on the name).

It chronicles the life of a lawyer – named Saul Goodman – who struggles to make his way in the grey world of the law profession. He fights to survive by taking the information he has, and using it to plead his cases. But sometimes the original pieces of information he is dealing with are not always what they appear to be.

A similar situation faces researchers the world over.

Every day new information is reported. And this process is unrelenting. It simply never stops.

For Parkinson’s research alone, every day there is about 20 new research reports (approximately 120 per week).

But determining what is ‘usable’ information relies on independent replication. And sometimes efforts to validate a new finding fail to reproduce the initially reported results.

An example of this has occurred recently in the world of Parkinson’s research, with some rather large implications.

What happened?

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