This week a group of scientists have published an article which indicates differences between mice and human beings, calling into question the use of these mice in Parkinson’s disease research.
The results could explain way mice do not get Parkinson’s disease, and they may also partly explain why humans do.
In today’s post we will outline the new research, discuss the results, and look at whether Levodopa treatment may (or may not) be a problem.
The humble lab mouse. Source: PBS
Much of our understanding of modern biology is derived from the “lower organisms”.
From yeast to snails (there is a post coming shortly on a snail model of Parkinson’s disease – I kid you not) and from flies to mice, a great deal of what we know about basic biology comes from experimentation on these creatures. So much in fact that many of our current ideas about neurodegenerative diseases result from modelling those conditions in these creatures.
Now say what you like about the ethics and morality of this approach, these organisms have been useful until now. And I say ‘until now’ because an interesting research report was released this week which may call into question much of the knowledge we have from the modelling of Parkinson’s disease is these creatures.
You see, here’s the thing: Flies don’t naturally develop Parkinson’s disease.
Nor do mice. Or snails.
Or yeast for that matter.
So we are forcing a very un-natural state upon the biology of these creatures and then studying the response/effect. Which could be giving us strange results that don’t necessarily apply to human beings. And this may explain our long history of failed clinical trials.
We work with the best tools we have, but it those tools are flawed…
What did the new research report find?
This is the study:
Title: Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease
Authors: Burbulla LF, Song P, Mazzulli JR, Zampese E, Wong YC, Jeon S, Santos DP, Blanz J, Obermaier CD, Strojny C, Savas JN, Kiskinis E, Zhuang X, Krüger R, Surmeier DJ, Krainc D
Journal: Science, 07 Sept 2017 – Early online publication
The researchers who conducted this study began by growing dopamine neurons – a type of cell badly affected by Parkinson’s disease – from induced pluripotent stem (IPS) cells.
What are induced pluripotent stem cells?
The image above presents a ‘before treatment’ (left) and ‘after treatment’ (right) brain scan image from a recent research report of a clinical study that looked at the use of Acetylcysteine (also known as N-acetylcysteine or simply NAC) in Parkinson’s disease.
DaTscan brain imaging technique allows us to look at the level of dopamine processing in an individual’s brain. Red areas representing a lot; blue areas – not so much. The image above represents a rather remarkable result and it certainly grabbed our attention here at the SoPD HQ (I have never seen anything like it!).
In today’s post, we will review the science behind this NAC and discuss what is happening with ongoing clinical trials.
Source: The Register
Let me ask you a personal question:
Have you ever overdosed on Paracetamol?
Regardless of your answer to that question, one of the main treatments for Paracetamol overdose is administration of a drug called ‘Acetylcysteine’.
Why are you telling me this?
Because acetylcysteine is currently being assessed as a potential treatment for Parkinson’s disease.
Oh I see. Tell me more. What is acetylcysteine?
Acetylcysteine. Source: Wikimedia
Acetylcysteine (N-acetylcysteine or NAC – commercially named Mucomyst) is a prodrug – that is a compound that undergoes a transformation when ingested by the body and then begins exhibiting pharmacological effects. Acetylcysteine serves as a prodrug to a protein called L-cysteine, and – just as L-dopa is an intermediate in the production of dopamine – L-cysteine is an intermediate in the production of another protein called glutathione.
Take home message: Acetylcysteine allows for increased production of Glutathione.
What is glutathione?
Glutathione. Source: Wikipedia
Glutathione (pronounced “gloota-thigh-own”) is a tripeptide (a string of three amino acids connected by peptide bonds) containing the amino acids glycine, glutamic acid, and cysteine. It is produced naturally in nearly all cells. In the brain, glutathione is concentrated in the helper cells (called astrocytes) and also in the branches of neurons, but not in the actual cell body of the neuron.
It functions as a potent antioxidant.