$161 million over three years

 

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The Aligning Science Across Parkinson’s (or ASAP) initiative is a major new source of funding for Parkinson’s research. And I mean MAJOR!

It is a global basic research initiative focused on fostering collaboration and resources to better understand the underlying causes of Parkinson’s. A return to basics in order to get a better grip on the biology of the disease.

Recently, the initiative announced their first round of grant awardees – handing out US$161 million for 3 year projects. This is one of the largest single rounds of research funding for Parkinson’s research ever!

In today’s post, we will look at what ASAP is, what the awarded projects will be investigating, and what this means for Parkinson’s research.

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NIH Parkinson’s research funding. Source: NIH

In 2016, the US National Institutes of Health (NIH – the world’s largest funder of medical research) allocated $161 million to Parkinson’s research.

It was a small fraction of the $30+ billion spent by the NIH on medical research that year, but it was still a much needed amount of money invested into research on this neurodegenerative condition.

This week, a major new Parkinson’s research program – called Aligning Science Across Parkinson’s (or ASAP – click here to read a previous SoPD post on this initiative) – announced the rewarding of $161 million in research funding to 21 projects involving 96 research leaders from 60 institutions across 11 countries (and 31 of the research leaders are female). Importantly, all of them are seeking to “accelerate targeted basic research and move us toward more meaningful advancements for Parkinson’s” (Click here to read the annoucement).

Think about that for a second:

ASAP has basically just allocated the same amount of funding to Parkinson’s research as the entire US Government did in 2016.

Wow!

Continue reading “$161 million over three years”

ROPAD + LIPAD = NOT BAD :)

 

 

 

Approximately 10-20% of Parkinson’s cases are associated with a genetic risk factor which raises the chances of developing the condition.

Tremendous efforts are being made to not only better understand the underlying biology of these associations, but also to identify individuals who may be affected and invite them to take part in innovative new clinical trials.

The challenge is significant, however, as some genetic risk factors only affect less than 1% of the Parkinson’s community, meaning that hundreds of individuals must be genetically screened in order to identify 1 or 2 who might be eligible to take part in any subsequent study.

In today’s post, we will look at one such project (called the “Rostock International Parkinson’s Disease” (or ROPAD) study, and how it is helping to facilitate a second effort called the “LRRK2 International Parkinson’s Disease” (or LIPAD) project.

 


Rostock: Source: Lerbs

With 200,000+ inhabitants, Rostock was the third largest coastal city in Germany (after Kiel and Lübeck). The city lies on the estuary of the River Warnow in the Bay of Mecklenburg.

Each year, during the second weekend in August, Rostock holds one of the largest yachting events in the world: The Hanse Sail. It is a maritime celebration which attracts more than a million visitors and traditional sailing boats from all over the world.

Source: Hansetag-rostock

Rostock is also home to a company called Centogene.

What does Centogene do?

In 2006, neurologist Arndt Rolfs wanted to speed up the diagnosis of rare diseases. To do this, he founded Centogene. The company now has more than 300 employees and has built up one of the world’s largest data repository for genetic information on rare hereditary diseases. It sells genetic testing products and helps pharmaceutical firms develop new drugs for rare conditions.

It is also an instrumental part of a new Parkinson’s research project called ROPAD.

What is ROPAD?

Continue reading “ROPAD + LIPAD = NOT BAD :)”

Something LRRKing in the immune system

 

 

Canadian scientists recently reported that mice with a specific genetic variation – in the Parkinson’s-associated LRRK2 gene – differ in how they are able to deal with bacterial and viral infections.

Curiously, mice with the Parkinson’s-associated LRRK2 mutation could handle a bacterial infection better than normal mice, while mice with no LRRK2 protein struggled against the infection. And the researchers found that this effect was most prominent in female mice in particular.

And curiously, when the mice are infected with a dangerous virus, female mice with the Parkinson’s-associated LRRK2 mutation fared worse than their male counterparts.

In today’s post, we will discuss what LRRK2 is, review the new research, and explore what the sex difference could mean in terms of Parkinson’s.

 


Autumn colours. Source: Visitsunlimited

I am a big fan of Autumn.

The colours and the crisp/bracing air. I love the long, slow afternoon strolls and anticipation of the festive season to come.

But most of all I love the license to eat all the good wintery food. After a summer of salads and light food, there is nothing better that entering a warm cottage or pub, and smelling the hearty food (my wife if French – we navigate based on the quality of eateries).

Autumn bliss. Source: Askdrake

But there is a down side to autumn: The start of the flu season.

Luckily, our immune systems are pretty robust – doing battle on a moment-to-moment basis with all manner of pathogenic agents.

Recently, some Canadian scientists discovered something interesing about the immune system and it relates to Parkinson’s.

What did they find?

Continue reading “Something LRRKing in the immune system”

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?

Continue reading “Making sense of antisense”

AdoCbl + LRRK2 = modulation

 

Approximately 1 person with Parkinson’s in every 100 will have a genetic variation in a specific section of their DNA that is referred to as LRRK2 – pronounced ‘lark 2’. The variation results in changes to the activity of the LRRK2 protein, and these changes are suspected of influencing the course of LRRK2-associated Parkinson’s.

Numerous biotech companies are now developing LRRK2 targetting agents that will modulate the activity of the LRRK2 protein.

Recently, however, a research report was published which points towards a potentially accessible method of LRRK2 modulation – one of the active forms of vitamin B12 – and if this research can be independently replicated, it may provide certain members of the Parkinson’s community with another means of dealing with the condition.

In today’s post, we will look at what LRRK2 is, review the new research, and discuss what could happen next.

 


This is Sergey Brin.

You may have heard of him – he was one of the founders of a small company called “Google”. Apparently it does something internet related.

Having made his fortune changing the way we find stuff, he is now turning his attention to other projects.

One of those other projects is close to our hearts: Parkinson’s.

Why is he interested in Parkinson’s?

In 1996, Sergey’s mother started experiencing numbness in her hands. Initially it was believed to be a bit of RSI (Repetitive strain injury). But then her left leg started to drag. In 1999, following a series of tests and clinical assessments, Sergey’s mother was diagnosed with Parkinson’s.

The Brin Family – Sergey and his mother on the right. Source: CS

It was not the first time the family had been affected by the condition – Sergey’s late aunt had also had Parkinson’s.

Given this coincidental family history of this particular condition, both Sergey and his mother decided to have their DNA scanned for any genetic errors (also called ‘variants’ or ‘mutations’) that are associated with an increased risk of developing Parkinson’s. And they discovered that they were both carrying a genetic variation in a gene (a section of DNA that provides the instructions for making a protein) called PARK8 – one of the Parkinson’s-associated genes (Click here to read more about the genetics of Parkinson’s and the PARK genes).

The PARK8 gene is also known as Leucine-rich repeat kinase 2 (or LRRK2 – pronounced ‘lark 2’).

What is LRRK2?

Continue reading “AdoCbl + LRRK2 = modulation”

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.

Continue reading “A Lewy body condition?”

New LRRK2 results: Game changer?

 

Millions of dollars in research funding for Parkinson’s has been poured into the biology and function of just one hyperactive protein. It is called Leucine-rich repeat kinase 2 (or LRRK2). Genetic mutations in the gene that gives rise to this abnormal version of the protein can leave carriers with a higher risk of developing Parkinson’s. 

All of that research funding has resulted in an incredible leap forward in our understanding of LRRK2, which has further led to clinical trials focused solely on LRRK2. Mutations in the LRRK2 gene occur in only 1-2% of the Parkinson’s population, however, which has led to some complaints that too much research is being focused on only a small fraction of the people affected by PD.

New research published this week could silence those complaints.

In today’s post we will discuss a new report suggesting that independent of any genetic mutations, LRRK2 may actually play a role in idiopathic (or spontaneous) forms of Parkinson’s, which means that the treatments being developed for LRRK2 could be beneficial for a wider section of the PD community.

 


sergey_brin

This is Sergey Brin.

He’s a dude.

You may have hear of him – he was one of the founders of a small company called “Google”.

Having changed the way the world searches the internet, he is now turning his attention to other projects.

One of those other projects is close to our hearts: Parkinson’s.

Why is he interested in Parkinson’s?

Continue reading “New LRRK2 results: Game changer?”

“What’s the evolutionary advantage of Parkinson’s?”

Each year King’s College London holds the Edmond J. Safra Memorial Lecture. It is a public event – exploring cutting-edge research on Parkinson’s – held in honour of the late philanthropist and financier, Mr Edmond J Safra, .

I was lucky enough to attend this year’s event (entitled A vision of tomorrow: How can technology improve diagnosis and treatment for Parkinson’s patients?). It highlighted the fantastic research being carried out by Professor Marios Politis and his team.

During the Q&A session of the event though, a question was asked from the audience regarding what the evolutionary advantage of Parkinson’s might be. The question drew a polite chuckle from the audience.

But the question wasn’t actually as silly as some might think.

In today’s post we look at some evidence suggesting an evolutionary advantage involving Parkinson’s.


King’s College London Chapel. Source: Schoolapply

Despite the impressive name, King’s College London is not one of the grand old universities of England.

Named after its patron King George IV (1762-1830), the university was only founded in 1829 (compare this with 1096 for Oxford and 1209 for Cambridge; even silly little universities like Harvard date back further – 1636). The university is spread over five separate campuses, geographically spread across London. But if you ever get the chance to visit the main Strand campus, ask for the chapel and take a moment to have a look – it is very impressive (the image above really doesn’t do it justice).

As I mentioned in the intro, each year King’s College London holds the Edmond J. Safra Memorial Lecture. It is an event that is open to the public and it involves a discussion regarding innovative new research on Parkinson’s. The evening is held in honour of the late Mr Edmond J Safra.

Edmond J. Safra. Source: Edmondjsafrafoundation

This year, Professor Marios Politis and members of his research group were presenting lectures on “How can technology improve diagnosis and treatment for Parkinson’s”. The lectures were very interesting, but the reason I am writing about it here is because during the question and answer session at the end of the lectures, the following question was asked:

“What’s the evolutionary advantage of Parkinson’s?”

Given the debilitating features of the condition, the audience was naturally amused by the question. And there was most likely several people present who would have thought the idea of any evolutionary advantage to Parkinson’s a ridiculous concept.

But it’s not.

And there is actually research to suggest that something evolutionary could be happening with Parkinson’s.

?!?!? What do you mean?

Continue reading ““What’s the evolutionary advantage of Parkinson’s?””

Inhibiting LRRK2: The Denali Phase I results

Denali

This week Denali Therapeutics released the results of a phase I clinical trial of their primary product, called DNL-201.

DNL-201 is a LRRK2 inhibitor that the company is attempting to take to the clinic for Parkinson’s disease. 

In today’s post we will look at what LRRK2 is, how an inhibitor might help in Parkinson’s, and what the results of the trial actually mean.


Wonder_Lake_and_Denali

Denali. Source: Wikipedia

Denali (Koyukon for “the high one”; also known as Mount McKinley) in Alaska is the highest mountain peak in North America, with a summit elevation of 20,310 feet (6,190 m) above sea level. The first verified ascent to Denali’s summit occurred on June 7, 1913, by four climbers Hudson Stuck, Harry Karstens, Walter Harper, and Robert Tatum.

Tatum (left), Karstens (middle), and Harper (right). Source: Gutenberg

Robert Tatum later commented, “The view from the top of Mount McKinley is like looking out the windows of Heaven!”

More recently another adventurous group associated with ‘Denali’ have been trying to scale lofty heights, but of a completely different sort from the mountaineering kind.

Continue reading “Inhibiting LRRK2: The Denali Phase I results”

The LRRK Ascending

Genetic mutations (or ‘variants’) in the Leucine-rich repeat kinase 2 (or LRRK2; also known as Dardarin) gene are associated with increased risk of Parkinson’s. As a result this gene has become the focus of a lot of genetic research.

But what about LRRK2’s less well-known, rather neglected sibling LRRK1?

In today’s post, we will look at new research that suggests the LRRK siblings could both be involved with Parkinson’s disease. 


I recommend to the reader that today’s post should be read with the following music playing in the background:

Inspired by a poem of the same title, English composer Ralph Vaughan Williams wrote ‘The Lark Ascending’ in 1914. It is still to this day, a tune that remains a firm favourite with BBC listeners here in the UK (Source).

On to business:

While the music and the poem are about a songbird, today’s SoPD post deals with a different kind of Lark.

Or should I say LRRK.

This is Sergey Brin.

sergey_brin

Nice guy.

He was one of the founders of a small company you may have heard of – it’s called “Google”.

Having changed the way the world searches the internet, he is now turning his attention to other projects.

One of those other projects is close to our hearts: Parkinson’s disease.

Continue reading “The LRRK Ascending”