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?
A research paper was published in the prestigious journal Cell this week that has some people excitedly suggesting that we are one step closer to living longer.
Age is the no. 1 correlate with neurodegenerative conditions like Parkinson’s disease. A better understanding of the ageing process would greatly aid us in understanding these conditions.
In today’s post we will review the research paper in question and discuss what it will mean for Parkinson’s disease.
Henrietta Lacks with her husband David. Source: HuffingtonPost
The lady in this photo is basically immortal.
Henrietta Lacks was an African American woman who died in October, 1951, but (it could be argued) lives in almost every research institute in the world. Henrietta died with cervical cancer, and during her treatment, she had a (unethical) biopsy conducted on her tumor which give rise to the first human immortalised cell line that is named after her: Hela cells (Henrietta Lacks).
And I kid you not when I say that there are samples of Hela cells in a freezer in almost every research institute in the world. Since the 1950s, scientists have grown 20 tons (and counting) of her cells (Source). And some of our greatest advances have been made with Hela cells, for example in 1954, Jonas Salk used HeLa cells in his research to develop the polio vaccine.
Unwittingly, Henrietta achieved immortality.
Hercules fighting off death. Source: ProactionaryTranshumanist
We humans have a strange fascination with immortality. It could be argued that it underlies our religions, and also drives us to achieve great things during our live times.
During the last three decades, science has begun probing the biology of ageing with the goal of helping us to understand how and why our bodies degrade over time in the hope that it will lead to better treatments for disease that predominantly affect the elderly.
Last week research groups from Spain and the Salk institute in California published the results of a study that may be considered the first tentative steps towards actually extending life and perhaps reversing the ageing process.
This is the article:
Title: In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming.
Authors: Ocampo A, Reddy P, Martinez-Redondo P, Platero-Luengo A, Hatanaka F, Hishida T, Li M, Lam D, Kurita M, Beyret E, Araoka T, Vazquez-Ferrer E, Donoso D, Roman JL, Xu J, Rodriguez Esteban C, Nuñez G, Nuñez Delicado E, Campistol JM, Guillen I, Guillen P, Izpisua Belmonte JC.
Journal: Cell. 2016 Dec 15;167(7):1719-1733.
In their study, the researchers used something called the ‘Yamanaka factors’ to try and reverse the ageing process in mice.
What are the Yamanaka factors?
This is Prof Shinya Yamanaka:
Source: Glastone Institute
He’s a dude.
In 2012 he and Prof John Gurdon (University of Cambridge) were awarded the Nobel prize for Physiology and Medicine for the discovery that mature cells can be converted back to stem cells. Prof Gurdon achieved this feat by transplanting a young nucleus into an old cell, while Prof Yamanaka did the same thing with the ‘Yamanaka factors’.
The Yamanaka factors are a set of 4 genes (named Myc, Oct3/4, Sox2 and Klf4) that when turned on in a mature cells (like a skin cell) can force the cell to ‘de-differentiate’ back into an immature cell that is capable of becoming any kind of cell. This induced un-programmed state means that the once adult cell has changed into something similar to an embryonic stem cell.
This new cell is called an induced pluripotent stem (IPS) cell – ‘pluripotent’ meaning capable of any fate.
So what did the researchers in the Cell paper do with the Yamanaka factors?
A lab mouse. Source: USNews
They genetically engineered mice that produced the Yamanaka factors in every cell in the body. They could turn on the Yamanaka factors by adding a special chemical to the drinking water of the mice for 2 out of every 7 days.
By turning on the 4 genes in this manner, the researchers found that they could extend the life span of the mice by 30%. In human terms, this would increase the average age of death from the current 80 years to 105 years!
Not only did they not the increase in the life span of the mice, but the researchers also found that the reprogramming of cells improved the regenerative ability of the cells in the aged mice. They even demonstrated this in human cells carrying the Yamanaka factors.
The study is very artificial – the mice and the human cell lines were engineered to produce the Yamanaka factors, which does not happen in normal nature – and we won’t be seeing any clinical trial for this kind of approach anytime soon. But the results will have big implications for the field of neurodegeneration.
Ok, but what has all this got to do with Parkinson’s disease?
Remember that the no. 1 correlate (association) with Parkinson’s disease is age. That is to say, your risk of developing Parkinson’s disease increases with age.
So this begs the question: if we had a better understanding of the ageing process (or even just a concept of what ageing is), could we beat off Parkinson’s disease?
Until the research paper reviewed above was published last week, this was all just silly hypothetical stuff. Now that we can extend the lives of mice by 30%, however, do we need to start actually considering the hypothetical as possible?
Science has brought us along way and provided us with many wonderful things (I would be lost without my Apple ipod). But we are now interesting a strange new world where science is going beyond normal basic biology and this may allow us to reverse what was previously un-negotiable facts. We can argue till the cows come home over the ethics of letting people live longer, but there is tremendous potential to use this technology to deal with the neurodegenerative conditions currently affecting us.
This is all very speculative, but it will be interesting to see where this leads. Stay tuned.
The banner for today’s post was sourced from TechieKids