Tagged: GBA1

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?

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Making a strong case for GCase

Novel therapies are increasing being developed to focus on specific subtypes of Parkinson’s. The hope is that if they work on one type of Parkinson’s, then maybe they will also work on others.

Many of these new experimental treatments are focused on specific genetic subtypes of the condition, which involve having a specific genetic variation that increases one’s risk of developing Parkinson’s.

Increasing amounts of data, however, are accumulating that some of the biological pathways affected by these genetic variations, are also dysfunctional in people with sporadic (or idiopathic) Parkinson’s – where a genetic variation can not explain the abnormality.

In today’s post, we will review some new research that reports reductions in a specific Parkinson’s-associated biological pathway, and discuss what it could mean for future treatment of the Parkinson’s.


Source: Medium

I was recently at a conference on Parkinson’s research where a prominent scientist reminded the audience that just because a person with Parkinson’s carries certain genetic risk factor (an error in a region of their DNA that increases their risk of developing Parkinson’s), does not mean that their Parkinson’s is attributable that genetic variation. Indeed, lots of people in the general population carry Parkinson’s associated genetic risk factors, but never go on to develop the condition.

And this is a really important idea for the Parkinson’s community to understand: Most of the genetics of Parkinson’s deals with ‘association’, not with ‘causation’.

But that begs the question ‘if we do not know that these errors in our DNA are causing Parkinson’s, then why should we be trying to develop therapies based on their biology?’

It is a fair question (it is also a very deep and probing question to start a post off with!).

The genetics of Parkinson’s has been extremely instructive in providing us with insights into the potential underlying biology of the condition. We have learnt a great deal about what many of the biological processess thatare associated with these genetic risk factors, and (yes) various experimental therapies have been developed to target them.

These novel treatments are clinically tested in the hope that they will have beneficial effects not just on individuals carrying certain genetic risk factors, but also on the wider Parkinson’s community.

And recently, there has been increasing evidence supporting this possibility. Some of the biological pathways associated with these genetic mutations appear to also be abnormal in people with Parkinson’s who do not carry the genetic variation.

What do you mean?

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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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Don’t get mad! Get NAD!

Recently researchers have provided very interesting evidence that a form of vitamin B3, called Nicotinamide Riboside, may have beneficial effects for Parkinson’s.

Their data suggests that nicotinamide riboside was able to rescue problems in mitochondria – the power stations of cells – in both fly and human cell-based models of Parkinson’s.

And the results also suggest that this treatment could prevent the neurodegeneration of dopamine producing neurons.

In today’s post, we will discuss what nicotinamide riboside is, what is does in the body, how it may be having its beneficial effect, and we will consider the pros and cons of taking it as a supplement.


My pile of research reports to read. Source: Reddit

We have a serious problem in biomedical research at the moment.

Serious for ‘planet research’ that is (Good for ‘planet patient’! – click here to understand this sentence).

The problem is very simple: there is too much research going on, and there is now too much information to be absorbed. 

There has been an incredible increase in the number of research reports for ‘Parkinson’s’:

For Parkinson’s research alone, every day there is about 20 new research reports (approximately 120 per week). It used to be the case that there was one big research report per year. Then progress got to the crazy point of one big finding per month. And now things are ‘completely kray kray’ (as my 5 year old likes to say), with one new major finding every week!

On top of this, everyday there are new methodology reports, new breakthroughs in other fields that could relate to what is happening in PD, new clinical trial results, etc… The image below perfectly represents how many researchers are currently feeling with regards to the information flow:

How I feel most days. Source: Lean

Don’t get me wrong.

These are very exciting times, big steps are being made in our understanding of conditions like Parkinson’s. It’s just that it is really hard keeping up with the amazing flow of new data.

And this is certainly apparent here on the SoPD website. Occasionally, a few days after I publish something on a particular topic on the SoPD website, a fascinating new research report on that same topic will be published. When I get a chance to read it, I will sometimes add an addendum to the bottom of a post highlighting the new research.

Every now and then, however, the new research deserves a post all of its own.

Which is the case today.

A week after I published the recent Vitamin B3/Niacin post, a new study was published that dealt with a different form of Vitamin B3, called Nicotinamide Riboside. And the results of that study were really interesting.

Wait a minute. Vitamin B3 comes in different forms?

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When GCase is away, the GSLs will play

 

 

New research published in the last week provides further experimental support for numerous clinical trials currently being conducted, including one by the biotech company Sanofi Genzyme.

Researchers have demonstrated that tiny proteins which usually reside on the outer wall of cells could be playing an important role in the protein clustering (or aggregation) that characterises Parkinson’s

In today’s post we will look at this new research and discuss what it could mean for the on going clinical trials for Parkinson’s. 


Source: Stevedalepetworld

The proverb ‘When the cat is away, the mice will play’ has Latin origins.

Dum felis dormit, mus gaudet et exsi litantro (or ‘When the cat falls asleep, the mouse rejoices and leaps from the hole’)

It was also used in the early fourteenth century by the French: Ou chat na rat regne (‘Where there is no cat, the rat is king’).

And then Will Shakespeare used it in Henry the Fifth(1599), Act I, Scene II:

Westmoreland, speaking with King Henry V, Gloucester, Bedford, Exeter and Warwick
“But there’s a saying very old and true,
‘If that you will France win,
Then with Scotland first begin:’
For once the eagle England being in prey,
To her unguarded nest the weasel Scot
Comes sneaking and so sucks her princely eggs,
Playing the mouse in absence of the cat,
To tear and havoc more than she can eat”

The phrase first appears in its modern form in the United States in the literary and political magazine The Port folio in 1802 (2; 323):

Interesting. But what does any of this have to do with Parkinson’s?

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AAV-PHP.B: The future is apparently now

In addition to looking at current Parkinson’s disease research on this website, I like to look at where technological advances are taking us with regards to future therapies.

In July of this year, I wrote about a new class of engineered viruses that could potentially allow us to treat conditions like Parkinson’s disease using a non-invasive, gene therapy approach (Click here to read that post). At the time I considered this technology way off at some point in the distant future. Blue sky research. “Let’s wait and see” – sort of thing.

So imagine my surprise when an Italian research group last weekend published a new research report in which they used this futurist technology to correct a mouse model of Parkinson’s disease. Suddenly the distant future is feeling not so ‘distant’.

In today’s post we will review and discuss the results, and look at what happens next.


Technological progress – looking inside the brain. Source: Digitial Trends

I have said several times in the past that the pace of Parkinson’s disease research at the moment is overwhelming.

So much is happening so quickly that it is quite simply difficult to keep up. Not just here on the blog, but also with regards to the ever increasing number of research articles in the “need to read” pile on my desk. It’s mad. It’s crazy. Just as I manage to digest something new from one area of research, two or three other publications pop up in different areas.

But it is the shear speed with which things are moving now in the field of Parkinson’s research that is really mind boggling!

Source: Pinterest

Take for example the case of Squalamine.

In February of this year, researchers published an article outlining how a drug derived from the spiny dogfish could completely suppress the toxic effect of the Parkinson’s associated protein Alpha Synuclein (Click here to read that post).

The humble dogfish. Source: Discovery

And then in May (JUST 3 MONTHS LATER!!!), a biotech company called Enterin Inc. announced that they had just enrolled their first patient in the RASMET study: a Phase 1/2a randomised, controlled, multi-center clinical study evaluating a synthetic version of squalamine (called MSI-1436) in people with Parkinson’s disease. The study will enrol 50 patients over a 9-to-12-month period (Click here for the press release).

Source: Onemednews

Wow! That is fast.

Yeah, I thought so too, but then this last weekend a group in Italy published new research that completely changed my ideas on the meaning of the word ‘fast’. Regular readers will recall that in July I discussed amazing new technology that may one day allow us to inject a virus into a person’s arm and then that virus will make it’s way up to the brain and only infect the cells that we want to have a treatment delivered to. This represents non-invasive (as no surgery is required), gene therapy (correcting a medical condition with the delivery of DNA rather than medication). This new study used the same virus we discussed in July.

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