An exercise in expectations: Exenatide III

 

In August 2017, the results of a Phase II double-blind, placebo controlled clinical trial investigating whether the diabetes drug Exenatide (aka Bydureon) can be repurposed for the treatment of Parkinson’s were published.

Despite the fact that the study did not meet most of its end points, the Parkinson’s community got very excited about one of the results: The exenatide treated group demonstrated a stabilisation of their motor features over the 48 week trial, while the control group continued to worsen.

Over night, for many in the community, the hypothetical (a “disease-halting medication”) suddenly become a possibility. After such a long trail of negative clinical trial results, it was a very human and natural response for everyone to get excited. But with the news this month, that the Phase III exenatide clinical trial is about to start, the community needs to curb that excitement in order for a proper evaluation of the drug to take place.

In today’s post, we will look at the details of the new Phase III clinical trial for Exenatide and discuss why it is important to manage expections.

 


 

Here on the SoPD website we are often discussing novel potentially disease modifying therapies for Parkinson’s. And it is rather staggering the number and range of different approaches currently being tested on Parkinson’s.

And I am often asked, “Simon, if you were a betting man, which one I would put my money on? Which one are you expecting to work?

Now, before we go on dear reader, please understand that my answer to this question will problably disappoint you.

You see, I do not expect any of these experimental treatments being clinically tested to work.

WHAT THE?!?

Now, before you turn off, please let me explain – because this is important (it is not click-bait).

Ok, I’m listening. Why don’t you expect any of these treatments to work?!?

Continue reading “An exercise in expectations: Exenatide III”

Remembering Tom

 

On 31st May in 2017, Tom Isaacs – one of the co-founder of the the Cure Parkinson’s Trust – passed away suddenly.

It was a terrible shock for the Parkinson’s community, many of whom saw Tom as a leader of advocacy efforts.

In today’s post, two years after his passing, we remember Tom.

 


tom isaacs

Tom Isaacs

In 1996 – at just 27-years of age – Tom Isaacs, a London-based surveyor, was diagnosed with Parkinson’s. After dealing with the initial shock of it all, Tom embraced his situation and became a committed, (utterly) tireless activist.

He firstly walked the entire coastline of the UK to raise money and awareness for Parkinson’s. His book, “Shake well before use“, discusses that trip and his journey in adapting to life with Parkinson’s. It is a wonderful read – not only providing an intimate insight into the trials and tribulations of the condition, but also offering glimpses into the brilliant wit and humor of the man himself.

Upon returning from his epic walk, Tom (along with three other gentlemen with Parkinson’s) founded and set up the Cure Parkinson’s Trust.

Continue reading “Remembering Tom”

The Bristol GDNF results

 

Today – 27th February, 2019 – the long-awaited results of the Phase II GDNF clinical trial were published.

GDNF (or glial cell line-derived neurotrophic factor) is a protein that our bodies naturally produce to nurture and support cells. Extensive preclinical research suggested that this protein was particularly supportive of dopamine neurons – a group of cells in the brain that are affected by Parkinson’s.

The results of the Phase II clinical trial suggest that the treatment was having an effect in the brain (based on imaging data), but the clinic-based methods of assessment indicated no significant effect between the treatment and placebo groups.

In today’s post we will look at what GDNF is, review the previous research on the protein, discuss the results of the latest study, and look at what happens next.

And be warned this is going to be a long post!

 


Boulder, Colorado. Source: Rps

It all began way back in 1991.

George H. W. Bush was half way into his presidency, a rock band called Nirvana released their second album (‘Nevermind’), Michael Jordan and the Chicago Bulls rolled over the LA Lakers to win the NBA championship, and Arnold Schwarzenegger’s ‘Terminator 2’ was the top grossing movie of the year.

Source: Stmed

But in the city of Boulder (Colorado), a discovery was being made that would change Parkinson’s research forever.

In 1991, Dr Leu-Fen Lin and Dr Frank Collins – both research scientists at a small biotech company called Synergen, isolated a protein that they called glial cell-derived neurotrophic factor, or GDNF.

And in 1993, they shared their discovery with the world in this publication:

Title: GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.
Authors: Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F.
Journal: Science, 1993 May 21;260(5111):1130-2.
PMID: 8493557

For the uninitiated among you, when future historians write the full history of Parkinson’s, there will be no greater saga than GDNF.

In fact, in the full history of medicine, there are few experimental treatments that people get more excited, divided, impassioned and evangelical than GDNF.

This ‘wonder drug’ has been on a rollercoaster ride of a journey.

What exactly is GDNF?

Continue reading “The Bristol GDNF results”

The UP Study – UDCA in Parkinson’s

 

Today we received word of a new clinical trial for Parkinson’s being initiated here in the UK. This trial – named the UP study – will evaluate the safety and tolerability of a compound called Ursodeoxycholic acid (or UDCA – click here to read the press release).

UDCA is clinically available medication that is used in the treatment of gall stone, but recently there has been a large body of research suggesting that this compound may also have beneficial effects in Parkinson’s.

In today’s post, we will look at what UDCA is, discuss the preclinical research exploring UDCA, and outline the structure of the new clinical trial.

 


Source: Youtube

How often do you consider your gallbladder?

It is one of the less appreciated organs. A pear-shaped, hollow organ located just under your liver and on the right side of your body. Its primary function is to store and concentrate your bile. What is bile you ask? Bile is a yellow-brown digestive enzyme – made and released by the liver – which helps with the digestion of fats in your small intestine (the duodenum).

Source: Mayoclinic

One of the down sides of having a gall bladder: gallstones.

Gallstones are hardened deposits that can form in your gallbladder. About 80% of gallstones are made of cholesterol. The remaining 20% of gallstones are made of calcium salts and bilirubin. Bilirubin is the yellow pigment in bile. When the body produces too much Bilirubin or cholesterol, gallstones can develop.

Gallstones – ouch! Source: Healthline

About 10-20% of the population have gallstones (Source), but the vast majority experience no symptoms and need no treatment.

Interesting intro, but what does any of this have to do with Parkinson’s or a new clinical trial?

One of the treatments for gallstones is called UDCA. And today we found out that this compound is being clinically tested for “repurposing” as a treatment for Parkinson’s.

What is UDCA?

Continue reading “The UP Study – UDCA in Parkinson’s”

The Australian Parkinson’s Mission

 

At 9am on the 30th January, 2019, the Australian Government Federal Health Minister Greg Hunt announced the initiation of the ‘Australian Parkinson’s Mission‘ – a very massive $30 million clinical trial programme that will be focused on potentially disease modifying treatments for Parkinson’s.

This huge endeavour will being with a large multi-arm study – involving 300 hundred participants and investigating 4 drugs (compared to a single placebo). It will be a first of its kind project in the world targeting Parkinson’s.

This is a very exciting development for the Parkinson’s community!

In today’s post, we will discuss what we currently know about the Australian Parkinson’s Mission project, what we hope to see resulting from the initiative, and why this is a tremendous step forward for the international Parkinson’s community as a whole.

 


Source: Atom

Being a patriotic kiwi there is always enormous potential to make fun when writing a post about any Parkinson’s-related news coming out of Australia. New Zealand and Australia have always had a big brother/little brother kind of relationship (and just so we are clear: NZ is the big brother!).

But today is different.

It is very strange to say, but… today… I am actually very proud of you Australia.

At 9am this morning at the Garvan Institute of Medical Research in Sydney, Greg Hunt – the Federal Health Minister of the Australian Government – announced the commencement of a major clinical trial initiative (named ‘The Australian Parkinson’s Mission‘), which is going to be a very large, world-leading clinical programme focused on potentially disease modifying drugs for Parkinson’s (Click here to read the press release).

Struth mate!!! This sounds fantastic. What do we know about the study?

Continue reading “The Australian Parkinson’s Mission”

Exciting Exenatide Exosomes

 

Recent analysis of blood samples collected during the Phase II clinical trial of Exenatide in Parkinson’s has uncovered a very interesting finding that could have major implications for not only Parkinson’s, but for many different neurological conditions.

Exenatide is a treatment that helps to control glucose levels in people with diabetes. More recently, however, it has been suggested that this drug may also have beneficial effects in Parkinson’s. A collection of clinical trials in Parkinson’s are currently unway to test this idea.

The researchers who conducted a Phase II clinical trial of Exenatide in Parkinson’s have analysed ‘exosomes‘ collected from the blood of participants, and they found something rather remarkable.

In today’s post we will discuss what exosomes are, what the researchers found, and why their discovery could have major implications for all of neurological research.

 


 

Here on the SoPD website we have discussed at length the Phase II clinical trial of Exenatide in Parkinson’s (Click here, here and here to read more about this).

This week, however, researchers involved in the study reported yet another really interesting finding from the trial. And this one could have profound consequences for how we study not only Parkinson’s, but many other neurological conditions.

What did they find?

Last week this report was published:

Title: Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial.
Authors: Athauda D, Gulyani S, Karnati H, Li Y, Tweedie D, Mustapic M, Chawla S, Chowdhury K, Skene SS, Greig NH, Kapogiannis D, Foltynie T.
Journal: JAMA Neurol. 2019 Jan 14. doi: 10.1001/jamaneurol.2018.4304. [Epub ahead of print]
PMID: 30640362

In the Exenatide Phase II clinical trial, 60 people with moderate Parkinson’s were randomly assigned to receive either 2mg of Exenatide or placebo once weekly for 48 weeks followed by a 12-week washout (no treatment) period. The results suggested a stablisation of motor features over the 48 weeks of the study in the treated group (while the condition in the placebo group continued to progress).

During the study (which was conducted between June 2014 – June 2016), blood samples were collected at each assessement.

From those blood samples, serum was collected and analysed.

Remind me again, what is serum?

Continue reading “Exciting Exenatide Exosomes”