A rising tide with liraglutide

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A class of diabetes drugs called GLP-1 receptor agonists have exhibited neuroprotective properties in models of Parkinson’s, and a Phase IIb clinical trial produced encouraging.

This research has led to a number of parties to start investigating new and old GLP-1 receptor agonists for their potential to slow the progression of Parkinson’s.

Recently, the results of a second Phase II clinical trial investigating a GLP-1 agonist were announced. The agonist being tested was liraglutide. 

In today’s post, we will discuss what GLP-1 receptor agonists are, what research has been conducted in PD, and look at the recent clinical trial announcement.

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The name “Golden Goose Award” doesn’t really conjure images of an inspirational kind of accomplishment. It does not suggest the same kind of gravitas that the Nobel prize carries. 

In fact, it sounds rather comical: The golden goose award? Sounds like a children’s book writers award.

 And yet…

The Award was originally established in 2012 with the goal of celebrating researchers whose seemingly odd or obscure federally funded research turned out to have a significant and positive impact on society as a whole.

And despite the name, it is a very serious award – past Nobel prize winners (such as Roger TsienDavid H. Hubeland Torsten N. Wiesel) are among the awardees.

In 2013, it was awarded to Dr John Eng, an endocrinologist from the Bronx VA Hospital.

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Dr John Eng. Source: Health.USnews

What did Dr Eng do to deserve the award?

Continue reading “A rising tide with liraglutide”

Be one with Vitamin B1

 

 

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BEFORE WE START: There are some topics that I am reluctant to address on this website, because there are folks within the community who have extremely vested interests in them. Thiamine (or Vitamin B1) is one of those topics. Some members of the Parkinson’s community have indicated to me that high doses of this vitamin are helping them. If you are one of those people, I say ‘Wonderful! Do what works for you”.

To stem the endless flow of emails asking for thoughts on high dose thiamine, however, I am writing this post to outline what research has been done on this topic in the Parkinson’s field. If you are looking for answers on thiamine, you may be disappointed. I am doing this to be able to point all future inquires towards it. That said, let’s begin:

In today’s post, we will delve into what thiamine (or vitamin B1) is and what it does in the body, how it relates to Parkinson’s, and we will discuss what clinical research exists for supporting its use as a treatment for PD.

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The Ryūjō. Source: Wikipedia

On December 19th 1882, the Japanese Naval training ship Ryujo (“Prancing Dragon”) set sail from Shinagawa, Japan, and over the next 10 months it called in at New Zealand (yay!), Chile, and Peru.

During this routine training voyage, however, 169 members of a crew of 376 crew became very sick.

That’s almost half (45%) of the crew.

In fact, the situation on board the boat got so bad that they had to stop in Hawaii on the homeward leg, because too many of the crew were sick to continue the voyage. Sadly by the time they returned to Japan in October 1883, there were 25 less members of the crew as a result of death due to sickness (and remember this was just a training voyage).

What was the sickness?

The men were suffering from a condition called beriberi.

What is beriberi?

Beriberi comes from a Sinhalese phrase which translates to “weak, weak” or “I cannot, I cannot“. There are two forms of the condition: ‘wet’ beriberi and ‘dry’ beriberi. Wet beriberi involves a fast heart rate, shortness of breath, and leg swelling. Dry beriberi is characterised by numbness of the hands and feet, confusion, trouble moving the legs, and pain. It is often said that ‘Wet’ involves the heart and ‘Dry’ involves the brain.

Source: Pinterest

Both forms of the condition, however, are caused by a deficiency in vitamin B1 – also known as thiamine.

What is Vitamin B1?

Continue reading “Be one with Vitamin B1”

The Llama-nation of LRRK2

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Antibodies are tiny y-shaped markers used by the immune system to label foreign agents within the body. Once bound to something, antibodies can alert immune cells to come and remove the object. Antibodies can also inhibit the object from doing anything nasty, like infecting or damaging a cell.

Between species, different types of antibodies have been identified and over the last few decades, scientists have re-engineered this natural system for many different purposes, including medicinal therapy. 

Recently, researchers have developed a new type of antibody and used it to better understand the activity of a Parkinson’s-associated protein: LRRK2

In today’s post, we will discuss what antibodies are, explore some of the different types that exist, re-examine what LRRK2 is, and review the recent research report.

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Winter. Source: Sky

Her name is Winter.

And she is a brown coated llama who lives on a research farm near Ghent (Belgium), along with 130 other llamas. You have probably never heard of her, but she has been a critical component in the fight against COVID-19.

Winter (Center, looking left) and friends. Source: Uchicago

Back in 2016, scientists chose a nine-month-old “Winter” as the llama they would inject with spike proteins from SARS-CoV-1 and MERS-CoV viruses, in the hope that she would produce antibodies that could neutralize all coronaviruses.

Note the date – this is why basic research is important to fund.

Jump forward to early 2020, and some of the antibodies that Winter produced back in 2016 were tested on samples of a new coronavirus called SARS-CoV-2 (aka COVID-19). They were found to potently inhibit the virus and Winter’s antibodies appeared in a major research publication:

Title: Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies.
Authors: Wrapp D, De Vlieger D, Corbett KS, Torres GM, Wang N, Van Breedam W, Roose K, van Schie L; VIB-CMB COVID-19 Response Team, Hoffmann M, Pöhlmann S, Graham BS, Callewaert N, Schepens B, Saelens X, McLellan JS.
Journal: Cell. 2020 May 28;181(5):1004-1015.e15.
PMID: 32375025                     (This report is OPEN ACCESS if you would like to read it)

This is great, but what do llama antibodies have to do with Parkinson’s?

Continue reading “The Llama-nation of LRRK2”

Monthly research review – March 2022

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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 March 2022.

The post is divided into 10 parts based on the type of research:

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So, what happened during March 2022?

In world news:

March 1st – It was announced that the US Patent and Trademark Office ruled that the Broad Institute of MIT and Harvard will retain their intellectual property over the use of CRISPR-Cas9 gene editing in eukaryotes – invalidating filings by the University of California, the University of Vienna, and Emmanuel Charpentier on use in eukaryotes.

 

March 6th – As the world watched the disaster unravelling in Ukraine, the UK Government quietly dropped plans to double their ‘moon shot’ dementia research fund, cutting the amount from £160 million to £75 million instead (Source). Probably due to the fraud and “error” on COVID-19 spending (possibly as much as £16 billionSource). Well, at least no money was wasted on dodgy personal protective equipment (Source… I’m really no good at sarcasm).

 

March 16th – A cross-party report from the UK Government’s Digital, Culture, Media and Sport Committee criticised the UNBOXED: Creativity in the UK” event (also known as the “Festival of Brexit”) as “vague and shape-shifting“, saying that it lacked clear direction and was an “irresponsible use of public money“. Taking place between March and November, the event will cost £120 million (Source).

 

March 30th – “I give you the light of Eärendil, our most beloved star” – Using gravitational lensing, NASA’s Hubble Space Telescope scientists detected light from the farthest individual star ever seen to date. They named it Eärendil. The newly detected star is so far away that its light has taken 12.9 billion years to reach Earth (Click here to read more about this).

March 31st – The Russian Ruble returned to pre-Ukraine invasion levels demonstrating the amazingly power and effectiveness of Western “sanctions”…

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

In March 2022, there were 1098 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (3412 for all of 2022 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

Continue reading “Monthly research review – March 2022”

Parkinson’s research in Nigeria

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In an effort to highlight under-represented populations within the Parkinson’s community world-wide, today we will look at some recent research that has been conducted in the central African republic of Nigeria.

Nigeria is a nation of more than 200 million people. Despite a lower general life expectancy rate, the country does have a large Parkinson’s community. In an effort to help those individuals, local researchers are conducting studies – both preclinical and clinical. 

In today’s post, we will review some of that research and discuss a clinical trial being conducted in Nigeria.

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Nigeria. Source: Britannica

Nigeria has been called the “Giant of Africa”, and for good reason.

Between 1990 and 2019, the population of Nigeria surged from 95 million to 201 million.

It currently sits around 220 million and it is on track to increase to over 400 million by 2050 (when it will overtake the USA as the world’s third most populated country). All of these people – who speak over 500 different languages/dialects – live in an area of 923,769 square kilometres (356,669 sq mi).

That is equivalent to the triangular area of land between Chicago, New York and Atlanta in the US:

Source: Quora

The country boasts the largest gross domestic product (GDP) in Africa, with a GDP of approximately $450 billion – making it the 29th largest economy in the world (Source). The sizeable GDP is mainly driven by finance, transport, infrastructure, tourism, and a large abundance of crude oil.

Source: Guardian

With such a large economy and significant resources at hand, improving health care has become a key goal for Nigeria. It currently spends only 3% of its GDP on health (compared to 16% in the US – Source). And this is unfortunately reflected in a high infant mortality rate (74/1000 live births), high maternal mortality rate (560/100 000 live births), and low life expectancy (<53 years – Source).

Interesting, but what does this have to do with Parkinson’s?

Continue reading “Parkinson’s research in Nigeria”

From NADPARK to NOPARK

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Researchers in Norway recently published the results of a small pilot study investigating the therapeutic potential of a form of Vitamin B3 – called nicotinamide riboside – in people with Parkinson’s.

The results of that randomised, double-blind study were encouraging as they demonstrated that orally-administered nicotinamide riboside treatment could boost energy levels in the brain and reduce the amount of inflammatory signaling.

The study was small, but provides strong justification for a much larger, ongoing Phase II clinical trial evaluating the disease modifying potential of nicotinamide riboside in 400 people with Parkinson’s.

In today’s post, we will discuss what nicotinamide riboside is, review the results of the published study, and explore what the ongoing trial looks like.

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Tromso, Norway (best new year’s eve ever!). Source: Outdooractive

As you read, you may notice that there is a slight Norwegian theme running through today’s post.

And it begins with Conrad Elvehjem:

Conrad Elvehjem. Source: Aboutnad

Who was Conrad Elvehjem?

He was the son of Norwegian emigrants to the US, and in 1937, he published this report:

Title: The isolation and identification of the anti-black tongue factor. 1937 (reprinted).
Authors: Elvehjem CA, Madden RJ, Strong FM, Wolley DW.
Journal: J Biol Chem. 2002 Aug 23;277(34):e22.
PMID: 12243127              (This report is OPEN ACCESS if you would like to read it)

In this study, Elvehem and colleagues noted that when dogs get pellagra (a vitamin B₃ deficiency disease) due to a poor diet, their tongues would turn black. This curious feature provided the researchers with an assay to test different food extracts on the dogs and see which ones could rescue the animals from the “black tongue disease”.

Their efforts led to the discovery of two vitamins – Nicotinic acid (also known as niacin) and nicotinamide – which cured the “black tongue disease” in the dogs. They are both forms of “vitamin B3” and they are now recognised as precursors of nicotinamide adenine dinucleotide (or NAD+).

What is –

We’ll come to that in a minute. Just let me get the intro out of the way.

The discovery of two forms of vitamin B3 was remarkable. But it was what happened 67 years later that was even more remarkable, and it was announced in this study:

Title: Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans.
Authors: Bieganowski P, Brenner C.
Journal: Cell. 2004 May 14;117(4):495-502.
PMID: 15137942            (This report is OPEN ACCESS if you would like to read it)

In this study, the researchers announced the discovery of a third form of vitamin B3 and another precursor to NAD+.

That new precursor was nicotinamide riboside.

Ok, stop. What is nicotinamide riboside? And what is NAD+ and nicotinamide ade…nine dinuc…stuff?

Continue reading “From NADPARK to NOPARK”

GCase: Mutants matter?

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Tiny genetic variations in a region of DNA called the GBA gene are associated with an increased risk of developing Parkinson’s. The information in the GBA gene provides the instructions for making an enzyme (called GCase) which is involved with waste disposal inside of cells.

Individuals with Parkinson’s who carry a variation in their GBA gene typically have low levels of GCase activity, so researchers have been attempting to identify therapeutic molecules that will enhance the level and activity of GCase as an approach towards slowing the progression of Parkinson’s.

Recently, however, new research has provide novel insights into how the biology of GCase pathway may be affected in individuals with Parkinson’s who carry a GBA genetic variation. 

In today’s post, we will explain what the GBA gene and GCase enzyme are, review the new research, and consider the potential implications of these findings.

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Prof Sulzer. Source: Youtube

Professor David Sulzer is one individual in the scientific research community who truly fascinates me.

In addition to being at the absolute top of his game academically (he is a professor of Psychiatry, Neurology, Pharmacology at Columbia University and maintains a very large research group investigating neurodegenerative conditions), he is also a composer and musician with a discography that any professional artists would be extremely proud of (his recording alias is Dave Soldier).

He’s also written books (for example Music Math and Mind“).

Source: Twitter

Where he finds the time to do all of these thing I do not know, but I really like the combination of art and science.

Oh, and did I forget to mention the Thai Elephant Orchestra?

I’m sorry: The what?!?

Just watch:

They have released three CDs and the band grew up to 14 elephants.

Fascinating, but what does this have to do with Parkinson’s?

Continue reading “GCase: Mutants matter?”

Patients not patents

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Patent protection provides an inventor/discoverer with an exclusive right to prevent or stop others from commercially exploiting the patented invention for a set period of time.

Patents are supposed to encourage innovation by providing the patent holder with an unchallenged opportunity to develop and profit from an idea. But it could be argued that patents are increasingly generating more problems than they are solving. In addition, they have led to the hording of data, which reduces collaboration and further limits progress.

Luckily there are some ambitious efforts trying to change this.

In today’s post, we will discuss some examples of these efforts.

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The Venetian Patent Statute. Source: Wikipedia

Patents are a form of intellectual property that provide the holder with the legal right to block others from manufacturing or selling an invention during a limited period of time. In exchange, the patent holder will publicly disclose the invention.

The use of patents began on the 19th March, 1474 when the the Venetian Patent Statute was established in the Republic of Venice.

The republic of Venice (in red) across the Mediterranean. Source: Alchetron

The Venetian Patent Statute provided that patents may be granted for “any new and ingenious device, not previously made“, IF that invention was considered useful.

More recently, some folks in the research and legal worlds have started arguing that patents themselves are no longer “useful”.

Patents are suppose to encourage innovation, but in the US alone, the costs brought on by patent trolls (these are holding companies that acquire strategic patents and use legal threats to extract steep royalties) now amounts to 12% of business R&D spending (Source). It is literally blocking innovation rather than stimulating it – if there is no certainty of a profit to cover the cost of royalties, there will be no innovation.

Patent troll. Source: Medium

And patents also inhibit medical research.

Many biotech firms will stop working on novel potential therapies (and even block others from working on them) because there is not a long enough period of time left in the patent to make a “business case” for supporting it.

As we have discussed in a previous post here on the SoPD, 30% of all Phase II clinical trials do not continue on to Phase III not because the therapy fails in terms of efficacy or safety, but rather the companies behind the agent can not find a business model that will justify continuing.

Pause and think about that for a moment.

1/3 of all Phase II trials…

…because limited profits can be made.

This is crazy. What can we do?

Continue reading “Patients not patents”

Are we Enterin a new age?

 

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A Parkinson’s-focused biotech company called Enterin has had a very busy start to the new year, with publication of some interesting preclinical research and the announcement of Phase II clinical trial results.

The clinical trial results met both the primary and secondary endpoints (the pre-determined measures of whether the treatment is effective) indicating a successful study, and the preclinical result provides new potential insights into the functions of the Parkinson’s-associated protein, alpha synuclein.

In today’s post, we will discuss both the clinical trial results and the preclinical work, and consider what this means for our understanding of Parkinson’s.

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Source: Discovery

In scientific nomenclature, they are referred to as Squalus acanthias.

Many people call them ‘Spurdogs’. Or ‘Mud sharks’. Or even ‘Piked dogfish’.

But they are more commonly known as spiny dogfish.

Source: X-ray Mag

Fun facts about spiny dogfish:

  1. They live in the shallow saltwater habitats of the North Pacific and the North Atlantic oceans
  2. The females are longer (49 inches or 124 cm) than the males (39 inches or 99 cm)
  3. They have two dorsal fins, both with venomous spines (hence the name)
  4. A pregnant females will have an average litter of 6 pups
  5. They have very long gestation periods – up to 24 months!
  6. The average lifespan ranges between 20 and 24 years
  7. Spiny dogfish are very fast swimmers – able to swim at about 6.2 feet/s (1.9 m/s)
  8. They have a special organ called the ‘Ampullae of Lorenzini‘ which they use to detect the electric field generated by their prey.
  9. They have a very keen sense of smell and two-thirds of their brain is involved in their sense of smell.

Oh, and they are extremely robust when it comes to infection.

Seriously, they never get sick, which is fascinating given that they have a relatively “primitive” immune system (Click here to read more on this).

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

Continue reading “Are we Enterin a new age?”

The mannitol clinical trial results

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Without a shadow of doubt, one of the most popular topics that readers search for on this website is ‘mannitol’. 

It is a widely used sweetner that became very popular in the Parkinson’s community after a 2013 research report presented compelling results that this molecule exhibited robust anti-aggregation properties on the Parkinson’s-associated protein alpha synuclein.

Recently the results of a carefully designed clinical trial evaluating mannitol have been published.

In today’s post, we will look at what mannitol is, review the previous research conducted on this agent in the context of Parkinson’s, and consider the results of the clinical trial.

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Source: History

During the forty years that the Israelites wandered the desert after leaving Egypt, they faced many hardships, most notably a scarcity of food. To resolve this particular issue, God kindly provided the Israelites with “bread from heaven”.

According to the scriptures, it was a “fine, flake-like thing, fine as frost on the ground” and “It was like coriander seed, white, and the taste of it was like wafers made with honey” (Exodus, Chapter 16).

They called “manna”.

Hence the phrase: Like manna from heaven

More recently, a substance called manna, has been the focus of a lot of attention in the Parkinson’s community.

A group of Israeli researchers have been exploring the potential of the sweetener ‘Mannitol’ (also known as Manna sugar) in the context of Parkinson’s.

What is mannitol?

Continue reading “The mannitol clinical trial results”