It is often said that only humans develop Parkinson’s. It is a distinctly human condiiton, and this is true (at the time of publishing this post).
But there are interesting Parkinson’s-related observations in the animal world that could tell us something about this ‘very human’ condition. We have previously highlighted reports of this nature (Click here for an example).
Recently Australian researchers have reported the accumulation of the Parkinson’s-associated protein alpha synuclein in the brains of kangaroos, after they ate a particular type of grass (phalaris pastures plants) which is toxic for them.
In today’s (short) post, we will discuss what the report found, look at what the plants contains, and consider what this could mean for our understanding of Parkinson’s.
The first interesting fact about kangaroos in today’s post: They are predominantly left handed
Researchers published a study in 2015 reporting that while most four legged marsupials show no preference between their limbs, kangaroos are very left handedness (Click here to read the report)
This finding is interesting as it could tell use much about our own handedness preference (Click here to read more about this).
Ok, interesting. But what on Earth does this have to do with Parkinson’s?
Ah, well that’s where we come to the second interesting fact about kangaroos in today’s post:
This week a new clinical trial was registered which caught our attention here at the SoPD HQ. It is being sponsored by a small biotech called Neuraly and involves a drug called NLY01.
NLY01 is a GLP-1R agonist – that is a molecule that binds to the Glucagon-like peptide-1 receptor and activates it. Other GLP-1R agonists include Exenatide (also called Bydureon) which is also also about to start a Phase III clinical trial in Parkinson’s (Click here to read a previous SoPD post about this).
There is a lot of activity in the Parkinson’s research world on GLP-1R agonists at the moment.
In today’s post, we will discuss what a GLP-1R agonist is, what we know about NLY01, and what the new clinical trial involves.
Every week there are new clinical studies being announced for Parkinson’s.
This week one particular newly registered clinical trial stood out. It involves a small biotech company Neuraly (which is owned by parent company D&D PharmaTech).
What is a GLP-1R agonist?
Stanford University researchers have recently published an interesting report in which they not only propose a novel biomarker for Parkinson’s, but also provide some compelling data for a novel therapeutic approach.
Their research focuses on a protein called Miro, which is involved in the removal of old or faulty mitochondria. Mitochondria are the power stations of each cells, providing cells with the energy they require to do what they do.
Specifically, the researchers found that Miro refuses to let go of mitochndria in people with Parkinson’s (which could act as a biomarker for the condition). They also found that pharmacologically forcing Miro to let go, resulted in neuroprotective benefits in models of Parkinson’s
In today’s post, we will discuss what Miro is, what the results of the new research suggest, and we will consider what will happen next.
Every now and then a research report comes along and you think: “Whoa, that’s amazing!”
It a piece of work that breaks down your cynicism (which you have proudly built up over years of failed experiments) and disciplined scepticism (a critical ingredient for a career in scientific research – mantra: ‘question everything’). And for a moment you are taken in by the remarkable beauty of not just good research, but biology itself.
A couple of weeks ago, one such research report was published.
This is it here:
Title: Miro1 Marks Parkinson’s Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson’s Models.
Authors: Hsieh CH, Li L, Vanhauwaert R, Nguyen KT, Davis MD, Bu G, Wszolek ZK, Wang X.
Journal: Cell Metab. 2019 Sep 23. [Epub ahead of print]
It’s a really interesting study for several reasons.
So what did they report?
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.
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?
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.
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
Previously researchers have described an intrinsic ultraviolet–visible optical property to amyloid proteins.
What does that mean?
Earlier this year, a San Francisco-based biotech company – called Cortexyme – published a research report that grabbed my attention.
The study presented data supporting an alternative theory of the cause of Alzheimer’s – one in which a bacteria involved in gum disease appears to be playing a leading role – and evidence that the company’s lead experimental compound COR388 could have beneficial effects in the treatment of the condition.
While the study was intriguing, what completely blew my mind was the fact that the company had already tested COR388 in a couple of Phase I clinical trials, and since then they have initiated a large Phase II/III trial.
In today’s post, we will discuss this new theory of Alzheimer’s, look at what Cortexyme are doing, and how this could relate to Parkinson’s.
The dashed lines show associations. Source: Slideplayer
Before we start today’s post, a word on ‘associations‘.
Please remember while reading this material that association does not equate to causation.
So if I write something like “researchers have found an association between a type of bacteria that causes gum disease and Alzheimer’s”, it does not mean that someone with either condition necessarily has the other. It only means that they have both simply appeared in the same individuals at a higher than chance rate.
So what is today’s post about?
A very interesting report in which researchers have found an association between a type of bacteria that causes gum disease and Alzheimer’s.
Researchers at the University of Cambridge have published an interesting research report last week regarding a clinically available drug that they suggest boosts autophagy in the brain.
Autophagy is one of several processes that cells use to dispose of waste and old proteins.
The drug is called Felodipine, and it is a calcium channel blocker that is used to treat high blood pressure.
In today’s post, we will look at what autophagy is, how boosting it could help with neurodegenerative conditions, and whether Felodipine should be clinically tested for re-purposing to Parkinson’s.
Prof Rubinsztein is the Deputy Director of the CIMR, the Academic Lead of the UK Alzheimer’s Research UK Cambridge Drug Discovery Institute, and he is a group leader at the UK Dementia Research Institute at the University of Cambridge.
He is also one of the world’s leading experts in the field of autophagy in neurodegenerative conditions.
What is autophagy?
Nuclear receptor related 1 protein (or NURR1) is a protein that has been shown to have a powerful effect on the survival of dopamine neurons – a population of cells in the brain that is severely affected by Parkinson’s.
For a long time researchers have been searching for compounds that would activate NURR1, but the vast majority of those efforts have been unsuccessful, leaving some scientists suggesting that NURR1 is “undruggable” (meaning there is no drug that can activate it).
Recently, however, a research report was published which suggests this “undruggable” protein is druggable, and the activator is derived from a curious source: dopamine
In today’s post, we will discuss what NURR1 is, what the new research suggests, and how this new research could be useful in the development of novel therapeutics for Parkinson’s.
It always seems impossible until it’s done – Nelson Mandela
In 1997, when Nelson Mandela was stepping down as President of the African National Congress, some researchers in Stockholm (Sweden) published the results of a study that would have a major impact on our understanding of how to keep dopamine neurons alive.
(Yeah, I know. That is a strange segway, but some of my recent intros have dragged on a bit – so let’s just get down to business)
Dopamine neurons are of the one groups of cells in the brain that are severely affected by Parkinson’s. By the time a person begins to exhibit the movement symptoms of the condition, they will have lost 40-60% of the dopamine neurons in a region called the substantia nigra. In the image below, there are two sections of brain – cut on a horizontal plane through the midbrain at the level of the substantia nigra – one displaying a normal compliment of dopamine neurons (on the left) and the other from a person who passed away with Parkinson’s demonstrating a reduction in this cell population (on the right).
The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinsonian brain (right). Source:Memorangapp
The researchers in Sweden had made an amazing discovery – they had identified a single gene (a specific region of DNA) that was critical to the survival of dopamine neurons. When they artificially disrupted the section of DNA where this gene lives – an action which resulted in no protein for this gene being produced – it resulted in mice being born with no midbrain dopamine neurons:
Title: Dopamine neuron agenesis in Nurr1-deficient mice
Authors: Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T.
Journal: Science. 1997 Apr 11;276(5310):248-50.
The researchers who conducted this study found that the mice with no NURR1 protein exhibited very little movement and did not survive long after birth. And this result was very quickly replicated by other independent research groups (Click here and here to see examples)
So what was this amazing gene called?
Nuclear receptor related 1 protein (or NURR1; it is also known as NR4A2 – nuclear receptor subfamily 4, group A, member 2)
And what is NURR1?
It is often said that Parkinson’s is a ‘distinctly human’ condition. Researchers will write in their reports that other animals do not naturally develop the features of the condition, even at late stages of life.
But how true is this statement?
Recently, some research has been published which brings into question this idea.
In today’s post, we will review these new findings and discuss how they may provide us with a means of testing both novel disease modifying therapies AND our very notion of what Parkinson’s means.
Checking his Tinder account? Source: LSE
Deep philosphical question: What makes humans unique?
Seriously, what differentiates us from other members of the animal kingdom?
Some researchers suggest that our tendency to wear clothes is a uniquely human trait.
The clothes we wear make us distinct. Source: Si-ta
But this is certainly not specific to us. While humans dress up to ‘stand out’ in a crowd, there are many species of animals that dress up to hide themselves from both predator and prey.
A good example of this is the ‘decorator crab’ (Naxia tumida; common name Little seaweed crab). These creatures spend a great deal of time dressing up, by sticking stuff (think plants and even some sedentary animals) to their exoskeleton in order to better blend into their environment. Here is a good example:
Many different kinds of insects also dress themselves up, such as Chrysopidae larva:
Dressed for success. Source: Bogleech
In fact, for most of the examples that people propose for “human unique” traits (for example, syntax, art, empathy), mother nature provides many counters (Humpback whales, bower birds, chickens – respectively).
So why is it that we think Parkinson’s is any different?
Wait a minute. Are there other animals that get Parkinson’s?
In today’s post we are going to look at a recent piece of research that suggests some of the bacteria in our gut can influence the availability of the medication we use to treat Parkinson’s.
In addition, we will look at a novel way researchers are re-engineering bacteria in the gut to correct other medical conditions (such as phenylketonuria) and we will ask if the same can not be applied to Parkinson’s.
The Platypus. Source: National geographic
The interesting, but utterly useless fact of the day: The duck-billed Platypus of Australia does not have a stomach.
No really. These oddities of evolution have no stomach. There’s no sac in the middle of their bodies that secrete powerful acids and digestive enzymes. The oesophagus (the tube from the mouth) of the platypus connects directly to its intestines.
The platypus. Source: Topimage
And believe it or not, platypus are not alone on this ‘sans estomac‘ trend. At least a 1/4 of the fish species on this planet do not have a stomach (Source).
And this absense of the stomach isn’t even remotely weird in the animal kingdom. Some creatures don’t even have a gastrointestinal system. No mouth. No anus. No intestines. Nothing.
The giant tube worm – Riftia pachyptila – lives on the floor of the Pacific Ocean, next to hot hydrothermal vents and can tolerate extremely high levels of hydrogen sulfide (hazardous for you and I). These creatures – which can grow up to 2.4 meters (or 7+ feet) in length – have no gastrointestinal tract whatsoever. Zip, zero, nada.
Rather they have an internal cavity – called a trophosome – filled with bacteria which live symbiotically with them.
Watch this video of Ed Yong explaining it all (great video!):
WOW! Fascinating! But what does ANY of this have to do with Parkinson’s?