Tagged: neurodegeneration

Man’s best friend

 

Recently it has been determined that many people with Parkinson’s have a distinct smell. It is a subtle odour that only some individuals with a very sensitive sense of smell can detect (Click here to read a previous SoPD post on this topic).

This curious discovery has given rise to a number of interesting research programmes which are trying to determine the underlying biology of the odour and how this knowledge could be useful in early detection of the condition and in our understanding of the disease.

In addition, there has been efforts to train dogs to detect the smell of Parkinson’s, and recently I was invited to visit a research centre that is teaching dogs to differentiate between odours, and identify the odour from people with Parkinson’s. It was a wonderful experience.

In today’s post, we will look at what the Medical Detection Dogs does and what implications their research could have for Parkinson’s.

 


Source: MDD

In my role of Deputy Director at the Cure Parkinson’s Trust I get invited to visit many interesting research efforts associated with Parkinson’s.

But recently there was one visit that I was particularly looking forward to.

A couple of weeks ago I drove up to Milton Keynes here in the UK and visited a charity called Medical Detection Dogs.

What do they do?

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Monthly Research Review – July 2019

EDITIORIAL NOTE: Apologies to readers for the lack of content on the SoPD website this month. At the Cure Parkinson’s Trust, we have been preparing dossiers for the Linked Clinical Trials meeting in August. I will explain this process and the initiative in a future post, but for now just understand that the preparation is a 7 days/week, 9am-2am marathon task – which has been left little time (or energy) for the SoPD.

In addition, I will be completely off the grid from the 1st August for 12 days, so expect further radio silence. No laptop. No phone (how will I survive?!?!). After that, we’ll be back to our regularly scheduled content (and a lot of catching up on recent research).

Kind regards, Simon

 

 

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 2019.

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

  • Basic biology
  • Disease mechanism
  • Clinical research
  • New clinical trials
  • Clinical trial news
  • Other news
  • Review articles/videos

 


So, what happened during July2019?

In world news:

1st-14th Juy – Wimbledon!

16th and 17th July – A partial lunar eclipse occurred. The Moon was covered about 65% by the Earth’s umbral shadow at maximum eclipse. This was the last umbral lunar eclipse until May 2021.

19th July – A week after cricketer Ben Stokes led England to beat New Zealand in an epic world cup final, some Kiwis nominated him for the New Zealander of the year award. Technically it works: He was born in NZ and lived there until he was 12, he apparently has Maori blood, and his parents still live there in NZ. Soooo… (Click here to read more about this).

31st July – concerns regarding the latest Ebola outbreak as the World Health Organization confirms a second person has died of the disease in Goma – a major transit hub in Democratic Republic of Congo (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 July 2019, there were 782 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5089 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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“Transdiagnostic” clusters

 

“In current models of neurodegeneration, individual diseases are defined by the presence of one or two pathogenic protein species. Yet, it is the rule rather than the exception that a patient meets criteria for more than one disease”

These are the first lines of a manuscript on the preprint sharing webiste BioRxiv, which analysed the co-occurance of biological markers of Alzheimer’s or Parkinson’s or other neurodegenerative conditions across 18 brain regions in 1389 postmortem brain from people who passed away with a neurodegenerative condition.

The results are interesting.

In today’s post, we will discuss what this study did, what is meant by “transdiagnostic disease clusters”, and consider what could they mean for our understanding of Parkinson’s… and heck, neurodegenerative conditions in general.

 


Malcolm Gladwell. Source: Masterclass

I am a fan of Malcolm Gadwell (not an endorsement, this is just me sharing).

He has a great way of looking at a situation from a completely different angle, finding things that no one else sees, and then writing about it in a clever, easy to read manner. Having read most of his books, I was rather pleased to learn that he has a podcast – Revisionist History.

And it’s good.

Oh boy, it’s good.

The first episodes of the most recent series of the podcast have helped to raise my fragile self esteem, because I am definitely a tortoise (just listen to the first two episodes of season 4 and you’ll understand).

Oh, and Mr Gladwell, if you ever read this – in the next series of the podcast, please have a look at the dysfunctional way we clinically test new therapies in medicine – click here to read a previous SoPD rant on this topic. Thanks!

What does Malcolm Gladwell have to do with Parkinson’s?

It all comes back to that idea of looking at a situation from a completely different angle.

What do you mean?

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Guten tag! MODAG

 

Last week the German biotech firm MODAG announced that they had secure €12M in series A funding from various venture capital investors.

The company is going to use those funds to clinically develop their lead compound – Anle138b – in the neurodegenerative condition, Multiple Systems Atrophy (or MSA). 

In today’s post, we will discuss how Anle138b works, what Multiple Systems Atrophy is, and how this news could be good for the Parkinson’s community.

 


Stealth mode. Source: Hackernoon

Last week a small biotech firm in Germany came out of ‘stealth mode’.

What is stealth mode?

According to wikipedia, “in business, stealth mode is a company’s temporary state of secretiveness, usually undertaken to avoid alerting competitors to a pending product launch or other business initiative”.

After years of developing a novel drug, the German company emerged from stealth mode with €12M in series A funding, which will be used to clinically test their new treatment.

The company’s name is MODAG.

And what is MODAG planning to do now they are out of “stealth mode”?

They are planning to clinically test their lead compound which is called Anle138b.

The initial Phase I safety test will be conducted in healthy individuals, but then they will turn their attention to individuals with multiple systems atrophy.

What is Multiple System Atrophy?

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Monthly Research Review – June 2019

 

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 2019.

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

  • Basic biology
  • Disease mechanism
  • Clinical research
  • New clinical trials
  • Clinical trial news
  • Other news
  • Review articles/videos

 


So, what happened during June 2019?

In world news:

7th June – British Prime Minister Theresa May resigned as leader of the Conservative Party… and then,… well, as if the BREXIT situation couldn’t get any worse…

9th June – The second reading on a controversial extradition bill in Hong Kong led to hundreds of thousands of people marching in protest.

(Photo:HECTOR RETAMAL/AFP/Getty Images)

14th June – NASA released a photo of a curious chevron shaped plateau on the surface of Mars which got Star Trek fans excited (Click here to read more about this).

21st June – A 2018 research report got a lot of folks excited when the BBC ran an article on how technology is changing our bodies. The article suggested that millenials are growing horns out of the back of their heads due to cell phone use. Needless to say, there are now concerns about the validity of the original results (Click here to read more about this).

22nd June – “Scamp the Tramp” was declared the winner of the 2019 ugliest dog contest (Click here to learn more about this).

 

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

In June 2019, there were 948 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4408 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 10 pieces of Parkinson’s news

(June is usually a quiet month – 2019 seems to be an exception)

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Dream, struggle, create, Prevail

 

The recent documents filed with the U.S. Securities and Exchange Commission by the biotech firm Prevail Therapeutics provides interesting insight into the bold plans of this company which was only founded in 2017.

Even more recent news that the U.S. Food and Drug Administration (FDA) has accepted the company’s Investigational New Drug (IND) application for its lead experimental treatment – PR001 – suggests that this company is not wasting any time. 

PR001 is a gene therapy approach targeting GBA-associated Parkinson’s.

In today’s post, we will discuss what GBA-associated Parkinson’s is, how Prevail plans to treat this condition, and discuss what we know about PR001.

 


Caterina Fake. Source: TwiT

The title of this post comes is from a quote by Caterina Fake (co-founder of Flickr and Hunch (now part of Ebay)), but it seemed appropriate.

This post is all about dreaming big (curing Parkinson’s), the struggle to get the research right, and to create a biotech company: Prevail Therapeutics.

What is Prevail Therapeutics?

Prevail is a gene therapy biotech firm that was founded in 2017.

The company was founded by Dr Asa Abeliovich:

Dr Asa Abeliovich. Source: Prevail

It was set up in a collaborative effort with The Silverstein Foundation for Parkinson’s with GBA (Click here to read a previous SoPD post about this organisation) and OrbiMed (a healthcare-dedicated investment firm).

What does Prevail Therapeutics do?

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I’m worried about my IMM-AGE

 

Researchers have recently described a new method to quantify a person’s “immune age” – a measure that could act as a key determinant of future health, as well as response to disease and treatment.

This novel test appears to provide a more reliable predictor for the status of one’s immune system than any other previous method.

And it could be useful in other ways.

In today’s post, we will discuss this new method of determining “immune age”, explore examples of how similar analysis has been used for other conditions, and consider what it could mean for Parkinson’s.

 


Source: Emaze

Do you remember Andre Agassi?

I know he’s still around, but when I was young and less beautiful, I was a big fan. Not only of his on court achievements, but also of his charismatic off-court image.

And it certainly paid off well for him:

One of the things that Agassi taught us was that “image is everything”.

Before Agassi, tennis was a conservative sport of white shirts & shorts (McEnroe was basically as radical as things got). It was bland, conservative, and – yes, I’ll say it – boring.

Agassi not only brought colour but charisma to the game. It was shocking and disgraceful to some, but to young, naive fools like me, it was a captivating breath of much needed fresh air.

Source: Hesaidandshesaid

Despite the early infatuation with the stylings of Mr Agassi, I have to admit that I have never remotely been concerned about own image. My dimensions mean that I wear what fits as opposed to what I like, and as a result the finished product is better behind a keyboard rather than speaking to a crowd.

But as I have gotten older, I have become concerned about a different kind of IMM-AGE (not a typo).

Let me explain: Recently some researchers in Israel and at Stanford University in the US published a rather remarkable research report which if replicated could have important implications for how we approach medical care.

What did they report?

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Making sense of antisense

 

Recent regulator approvals and exciting new preclinical data has refocused attention on a treatment approach for genetic conditions that has travelled a long and winding road towards clinical use.

Antisense oligonucleotides represent a method of altering protein levels at the post transcriptional level – it basically stops certain RNAs from being translated into protein.

And recently, a new clinical trial has been registered which will explore the use of this treatment approach in people with Parkinson’s.

In today’s post, we will look at what antisense oligonucleotides are, how they work, what research has been conducted in the context of Parkinson’s, and some of the limitations of this approach that still exist.

 


Source: Youtube

Spinal muscular atrophy (or SMA) is a genetic disorder that results in the degeneration of motor neurons in the spinal cord. This leads to progressive weakening and atrophy of muscules, ultimately leaving sufferers paralysed. It is caused by loss-of-function mutations in the survival motor neuron 1 (SMN1) gene.

It is a terrible condition that starts in very young children and has an incidence approaching 1:10,000 live births.

Luckily, novel therapies are being developed to deal with this condition, and in 2016, the US FDA approved a new treatment – following rather dramatic clinical trial results – called Nusinersen. This new therapy has caused a great deal of excitement as it basically halted the progression of SMA in many cases.

And a recent long term report highlights some of these very impressive results:

Title: Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies.
Authors: Darras BT, Chiriboga CA, Iannaccone ST, Swoboda KJ, Montes J, Mignon L, Xia S, Bennett CF, Bishop KM, Shefner JM, Green AM, Sun P, Bhan I, Gheuens S, Schneider E, Farwell W, De Vivo DC; ISIS-396443-CS2/ISIS-396443-CS12 Study Groups.
Journal: Neurology. 2019 May 21;92(21):e2492-e2506.
PMID: 31019106                (This report is OPEN ACCESS if you would like to read it)

Most importantly, Nusinersen is having real impact on the children who are affected by this condition:

Interesting, but what exactly is Nusinersen?

It is an antisense oligonucleotide.

What are antisense oligonucleotides?

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“So, will my head glow in a disco?”

 

The clustering (or aggregation) of misfolded proteins is a key feature of many neurodegenerative conditions. These aggregating proteins are collectively referred to as ‘amyloid’ proteins, and the way that they have misfolded allows many copies of these proteins to stick together.

Amyloid proteins are associated with more than 50 medical conditions (from Alzheimer’s, ALS, Huntinton’s and Parkinson’s through to rheumatoid arthritis and diabetes).

In addition to being public enemy no. 1 for their respective conditions, amyloid proteins also share another curious feature:

They glow when exposed to specific wavelengths of light (like near-infrared).

In today’s post, we will look at what we mean by ‘amyloid proteins’, what this new research found, and how this property could be extremely useful in the tracking of Parkinson’s over time.

 


Source: Yoursalesplaybook

If you have recently sent me an email, you may not have had a response. I apologise profusely for this, but I have gradually become inundated with questions and requests, and have had a hard time keeping up (in addition: family and day job take priority).

I do get some wonderfully titled emails though, which immediately grab the attention.

For example, the other day I recieved an email entitled:

“So, will my head glow in a disco?”

A brief glance at the contents confirmed suspicions that the sender was referring to this new research report:

Title: Ultraviolet–visible–near-infrared optical properties of amyloid fibrils shed light on amyloidogenesis
Authors: Pansieri J, Josserand V, Lee S-J, Rongier A, Imbert D, Sallanon MM, Kövari E, Dane TG, Vendrely C, Chaix-Pluchery O, Guidetti M, Vollaire J, Fertin A, Usson Y, Rannou P, Coll J-L, Marquette C, & Forge V
Journal: Nature Photonics, published 13th May 2019
PMID: N/A

Previously researchers have described an intrinsic ultraviolet–visible optical property to amyloid proteins.

What does that mean?

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WPC 2019 – Day 3

 

Today’s post is a recap of Day 3 – the final day – at the World Parkinson’s Congress meeting in Kyoto, Japan.

I will highlight some of the presentations I was able to catch and try to reflect on what was an amazing meeting.

 


The final day of the WPC meeting for me started with Parkinson’s advocate Heather Kennedy‘s presentation on “Your radical new life: Creative ways to overcome our challenges”. In her talk, she spoke of the mindset that is required for tackling Parkinson’s and provided some advice on what-to-do and what-not-to-do.

And Heather was speaking from personal experience. Having been diagnosed in 2012, she has become an active advocate, supporter of Davis Phinney and Michael J Fox Foundations, and an administrator on several online sites. And she regularly speaks about different methods for overcoming the challenges of Parkinson’s:

“It is not ‘why is this happening to me?’, it is ‘what is this teaching me?”

Here is a presenation she gave at the recent Parkinson’s Eve meeting in the UK earlier this year:

Key among her pieces of advice is the need to make connections:

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