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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A tiny dot with an anti-Parkinson’s plot

Graphene is widely being believed to be one of the building blocks of the future. This revolutionary 2D material is being considered for all kinds of applications, including those of a medicinal nature.

This week researchers from the John Hopkins University School of Medicine and Seoul National University have published a report suggesting that graphene may also have applications for Parkinson’s.

The researchers found that exposing the Parkinson’s-associated protein, alpha synuclein, to graphene quantum dots not only prevented the protein from aggregating together into its toxic form, but also destroyed the mature toxic form of it.

A nano-sized silver bullet?

In today’s post, we will look at what graphene quantum dots are, review the new Parkinson’s-related results, and discuss what happens next for this new technology.


Prof Andre Geim and Prof Konstantin Novoselov. Source: Aerogelgraphene

They called them ‘Friday night experiments’.

Each week, two research scientists at the University of Manchester (UK) named Andre Geim and Konstantin Novoselov held sessions where they would conduct experiments that had little or nothing to do with their actual research.

These activities were simply an exercise in genuine curiosity.

And on one particular Friday in 2004, the two scientists conducted one of the simplest experiments that they had ever attempted – but it was one which would change the world: They took some sticky tape and applied it to a lump of graphite.

What is graphite?

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Lipid issues in ER = ZZZ issues in PD

New research provides some interesting insight into particular cellular functions – and possibly sleep issues – associated with Parkinson’s.

Researchers in Belgium have recently published interesting findings that a genetic model of Parkinson’s exhibits sleep issues, which are not caused by neurodegeneration, but rather neuronal dysfunction. And as a result, they were able to treat it… in flies at least.

In today’s post, we will review this new research and consider its implications.


Source: Dlanham

I am a night owl.

One that is extremely reluctant to give up each day to sleep. There is always something else that can be done before going to bed. And I can often be found pottering around at 1 or 2am on a week night.

As a result of this foolish attitude, I am probably one of the many who live in a state of sleep deprivation.

I am a little bit nervous about doing the spoon test:

But I do understand that sleep is very important for our general level of health and well being. And as a researcher on the topic, I know that sleep complications can be a problem for people with Parkinson’s.

What sleep issues are there for people with Parkinson’s?

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The Big Hero 6 project

Inspiration comes from many different places.

For one young innovator it came from a character in a popular animated movie – an automated robot that could monitor and immediately diagnose medical conditions. This curious source of inspiration has now led to an award-winning piece of research involving artificial intelligence, machine learning, and a mobile app that can differentiate between people with and without Parkinson’s.

In today’s post, we will discuss this interesting unpublished research from an inspiring individual, who is trying to help us better diagnose and monitor Parkinson’s.


Source: Coub

Have you ever watched the movie ‘Big Hero 6‘?

It is the story of a boy named Hiro who goes on an adventure with a robot called Baymax.

Baymax is a personal healthcare companion that is designed to diagnose and treat medical conditions instantly.

After watching the movie Big Hero 6, Shreya Ramesh became fascinated with the idea of the character Baymax. She began wondering how a machine could be made to be smart enough to analyse the medical conditions, make a diagnosis, and then offer remedies.

So she began reading a great deal about machine learning and artificial intelligence technologies. Then she collected a large data set of information from people with and without Parkinson’s for analysis.

Source: Marketsimplified

Sounds interesting. Then what did she do?

Next, she designed, developed, and tested a smartphone application (using Python scripts) that could potentially one day help with early diagnosis of Parkinson’s.

Source: Dealnews

And Shreya presented her research at the Intel International Science and Engineering Fair, and she is now seeking to write up and publish her results in a scientific journal.

Wow. That’s really impressive!

Yeah. And she did all of this while still going to all her classes in high school.

Excuse me???

Oh, did I forget to mention that she’s just a high school student?

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The Chinese stem cell trial

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.



Brain surgery. Source Bionews-tx

As we have discussed before, any ‘cure’ for Parkinson’s requires 3 components:

  1. A disease halting mechanism – slowing or stopping the progression of the condition
  2. A neuroprotective agent – a treatment that will protect and support the remaining cells
  3. 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.

What is cell transplantation?

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Monthly Research Review – June 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 June 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 June 2018?

In world news:

June 12th – The 2018 North Korea–United States summit was held in Singapore. It was the first summit between a United States President and a North Korean leader.

June 14th – The 2018 FIFA World Cup started in Russia (unfortunately NZ did not qualify… so, go England!)

June 18th – Mexico football fans may have caused an earthquake in Mexico city while celebrating the win over Germany.

June 21st – New Zealand’s Prime Minister Jacinda Ardern gave birth to her first child, Neve Te Aroha Ardern Gayford. “Te aroha” is a Maori waiata (song) about love and peace.

 

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

In June 2018, there were 642 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4180 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 8 pieces of Parkinson’s news

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Squalamine begets Trodusquemine

Researchers at Cambridge University published a new report this week that extends on a very interesting line of Parkinson’s research. The studies focus on a compound (and derivatives of that compound) that has been derived from the dogfish shark.

The protein – called Squalamine – has an amazing ability to prevent the Parkinson’s-associated protein alpha synuclein from clustering (or aggregating) together. The aggregation of alpha synuclein is considered to be a key component of the biology underlying Parkinson’s, and thus any compound that block/reduce this aggregation is viewed with therapeutic applications in mind.

Unfortunately there is a problem with squalamine: it does not cross the blood brain barrier (the protective membrane surrounding the brain).

But a derivative of squalamine – called Trodusquemine – does!

In today’s post, we will look at what Squalamine and Trodusquemine are, we will review the new research, and look at current clinical research efforts involving these compounds.


The effects of aggregated Alpha Synuclein protein in a neuron. Source: R&D

We often talk about one particular protein on this website. It is called alpha synuclein. It is one of the most common proteins in the human brain, and it appears to be centrally involved with Parkinson’s.

In the Parkinsonian brain, alpha synuclein clumps (or aggregates) together, which is believed to lead to the appearance of Lewy bodies.

What are Lewy bodies?

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Monitoring Parkinson’s: Putting your finger on it

An important aspect of developing new potentially ‘curative’ treatments for Parkinson’s is our ability to accurately test and evaluate them. Our methods of assessing Parkinson’s at the moment 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 clinical testing and forever remain just  “potentially” curative.

Researchers from Madrid (Spain) and the Massachusetts Institute of Technology have developed new technology that could aid in better measuring and monitoring of Parkinson’s over time.

And it is as easy as typing on your keyboard or sending a text message.

In today’s post, we will look at how the monitoring of typing could provide a useful ‘real world’ method of assessing people with Parkinson’s over time.


Measuring stuff. Source: Medium

When we think about new technology for the monitoring of Parkinson’s, we all too often think of a device that is strapped on to the body in order to measure tremor or speed of movement (Click here to read a previous post on wearable tech).

Or perhaps a smart phone app that has simple tests on it that individuals can use to assess themselves over time (Click here to read a previous post on this topic).

One of the issues with these approaches, however, is ‘adherence‘ – these devices require effort from the individual being assessed (they have to strap on the motion sensing device or remember to complete the task on the smart phone). And after the first week or so of using the device or the app, the novelty wears off and recordings may be less frequent.

Many of these methods are also slightly ‘unnatural‘, and they may deviate the individual from their normal way of life. For example, wearable tech is amazing, but the individual may find it uncomfortable to wear all the time or may alter aspects of their behaviour to better suit the wearing of the device.

Source: Cloudtweaks

A better approach would be to have methods of monitoring that require no effort from the individual. Tools that silently and seamlessly slip into the background of their lives and monitor continuously – the individual completely forgets about them, which provides a more unbiased assessment.

We have previously discussed some examples of more ‘real world/natural’ approaches (such as smart pills – Click here to read that post – and also with regards to sleep monitoring – Click here to read that post), and today we will explore another example: keyboard stroke monitoring.

What is keyboard stroke monitoring?

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