Recently a Parkinson’s-associated research report was published that was the first of many to come.
It involves the use of a genetic screening experiment that incorporates new technology called ‘CRISPR’.
There is an absolute tidal wave of CRISPR-related Parkinson’s disease research coming down the pipe towards us, and it is important that the Parkinson’s community understands how this powerful technology works.
In today’s post we will look at what the CRISPR technology is, how it works, what the new research report actually reported, and discuss how this technology can be used to tackle a condition like Parkinson’s.
Me and my mother (and yes, the image is to scale). Source: Openclipart
My mother: Simon, what is all this new ‘crispy’ research for Parkinson’s I heard about on the news?
Me: Huh? (I was not really paying attention to the question. Terrible to ignore one’s mother I know, but what can I say – I am the black sheep of the family)
My mother: Yes, something about ‘crispy’ and Parkinson’s.
Me: Oh! You mean CRISPR. Yeah, it’s really cool stuff.
My mother: Ok, well, can you explain it all to me please, this ‘Crisper’ stuff?
CRISPR.101 (or CRISPR for beginners)
In almost every cell of your body, there is a nucleus.
It is the command centre for the cell – issuing orders and receiving information concerning everything going on inside and around the cell. The nucleus is also a storage bank for the genetic blueprint that provides most of the instructions for making a physical copy of you. Those grand plans are kept bundled up in 23 pairs of chromosomes, which are densely coiled strings of a molecule called Deoxyribonucleic acid (or DNA).
DNA’s place inside the cell. Source: Kids.Britannica
This week a biotech company called Voyager Therapeutics announced the results of their ongoing phase Ib clinical trial. The trial is investigating a gene therapy approach for people with severe Parkinson’s disease.
Gene therapy is a technique that involves inserting new DNA into a cell using a virus. The DNA can help the cell to produce beneficial proteins that go on help to alleviate the motor features of Parkinson’s disease.
In today’s post we will discuss gene therapy, review the new results and consider what they mean for the Parkinson’s community.
On 25th August 2012, the Voyager 1 space craft became the first human-made object to exit our solar system.
After 35 years and 11 billion miles of travel, this explorer has finally left the heliosphere (which encompasses our solar system) and it has crossed into the a region of space called the heliosheath – the boundary area that separates our solar system from interstellar space. Next stop on the journey of Voyager 1 will be the Oort cloud, which it will reach in approximately 300 years and it will take the tiny craft about 30,000 years to pass through it.
Where is Voyager 1? Source: Tampabay
Where is Voyager actually going? Well, eventually it will pass within 1 light year of a star called AC +79 3888 (also known as Gliese 445), which lies 17.6 light-years from Earth. It will achieve this goal on a Tuesday afternoon in 40,000 years time.
Gliese 445 (circled). Source: Wikipedia
Remarkably, the Gliese 445 star itself is actually coming towards us. Rather rapidly as well. It is approaching with a current velocity of 119 km/sec – nearly 7 times as fast as Voyager 1 is travelling towards it (the current speed of the craft is 38,000 mph (61,000 km/h).
Interesting, but what does any of that have to do with Parkinson’s disease?
Well closer to home, another ‘Voyager’ is also ‘going boldly where no man has gone before’ (sort of).
One of the most common observations that people make when they attend a Parkinson’s disease support group meeting is the huge variety of symptoms between sufferers.
Some people affected by this condition are more tremor dominant, while others have more pronounced gait (or walking) issues. In addition, some people have an early onset version, while others has a very later onset. What could explain this wide range of features?
A group of Stanford researchers have recently proposed an interesting new idea regarding our understanding of genetics that could partly explain some of this variability. In todays post I speculate on whether their idea could be applied to Parkinson’s disease.
Earlier this year an interesting study was published in the prestigious journal Nature on the topic of the genetics of height (yes height. Trust me, I’m going somewhere with this):
Title: Rare and low-frequency coding variants alter human adult height
Authors: Marouli E, Graff M, Medina-Gomez C, Lo KS, Wood AR, Kjaer TR, Fine RS, Lu Y, Schurmann C,………at least 200 additional authors have been deleted here in order to save some space…….EPIC-InterAct Consortium; CHD Exome+ Consortium; ExomeBP Consortium; T2D-Genes Consortium; GoT2D Genes Consortium; Global Lipids Genetics Consortium; ReproGen Consortium; MAGIC Investigators, Rotter JI, Boehnke M, Kathiresan S, McCarthy MI, Willer CJ, Stefansson K, Borecki IB, Liu DJ, North KE, Heard-Costa NL, Pers TH, Lindgren CM, Oxvig C, Kutalik Z, Rivadeneira F, Loos RJ, Frayling TM, Hirschhorn JN, Deloukas P, Lettre G.
Journal: Nature. 2017 Feb 9;542(7640):186-190.
In this study, the researchers – who are part of the GIANT consortium – were analysing DNA collected from over 700,000 people and trying to determine what genetic differences could influence height.
Height is not important for music. Source: Imgur
Why study height?
Good question. There are several reasons:
Firstly, it is easy to accurately measure. Second, the researchers believed that if we can master the complex genetics of something simple like height maybe what we learn will give us a blueprint for how we should study more complex medical disorders that have thus far eluded our complete understanding.
On the 27th June, 1997, a research report was published in the prestigious scientific journal ‘Science’ that would change the world of Parkinson’s disease research forever.
And I am not exaggerating here.
The discovery that genetic variations in a gene called alpha synuclein could increase the risk of developing Parkinson’s disease opened up whole new areas of research and eventually led to ongoing clinical trials of potential therapeutic applications.
Todays post recounts the events surrounding the discovery, what has happened since, and we will discuss where things are heading in the future.
It is fair to say that 1997 was an eventful year.
In world events, President Bill Clinton was entering his second term, Madeleine Albright became the first female Secretary of State for the USA, Tony Blair became the prime minister of the UK, and Great Britain handed back Hong Kong to China.
#42 – Bill Clinton. Source: Wikipedia
In the world of entertainment, author J. K. Rowling’s debut novel “Harry Potter and the Philosopher’s Stone” was published by Bloomsbury, and Teletubbies, South Park, Ally McBeal, and Cold Feet (it’s a British thing) all appeared on TV for the first time, amusing and entertaining the various age groups associated with them.
South Park. Source: Hollywoodreporter
Musically, rock band Blur released their popular hit song ‘Song 2‘ (released 7th April), “Bitter Sweet Symphony” by the Verve entered the UK charts at number 2 in June, and rapper Notorious B.I.G. was killed in a drive by shooting. Oh, and let’s not forget that “Tubthumping” (also known as “I Get Knocked Down”) by Chumbawamba was driving everybody nuts for its ubiquitous presence.
And at the cinemas, no one seemed to care about anything except a silly movie called Titanic.
Titanic. Source: Hotspot
Feeling old yet?
This is Lysimachos.
Pronounced: “Leasing ma horse (without the R)” – his words not mine.
He is one of the founders of an Edinburgh-based biotech company called “Parkure“.
In today’s post, we’ll have a look at what the company is doing and what it could mean for Parkinson’s disease.
The first thing I asked Dr Lysimachos Zografos when we met was: “Are you crazy?”
Understand that I did not mean the question in a negative or offensive manner. I asked it in the same way people ask if Elon Musk is crazy for starting a company with the goal of ‘colonising Mars’.
In 2014, Lysimachos left a nice job in academic research to start a small biotech firm that would use flies to screen for drugs that could be used to treat Parkinson’s disease. An interesting idea, right? But a rather incredible undertaking when you consider the enormous resources of the competition: big pharmaceutical companies. No matter which way you look at this, it has the makings of a real David versus Goliath story.
But also understand this: when I asked him that question, there was a strong element of jealousy in my voice.
Incorporated in October 2014, this University of Edinburgh spin-out company has already had an interesting story. Here at the SoPD, we have been following their activities with interest for some time, and decided to write this post to make readers aware of them.
There was an interesting new study published yesterday:
Title: Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns.
Author: Sanchez-Mut JV, Heyn H, Vidal E, Moran S, Sayols S, Delgado-Morales R, Schultz MD, Ansoleaga B, Garcia-Esparcia P, Pons-Espinal M, de Lagran MM, Dopazo J, Rabano A, Avila J, Dierssen M, Lott I, Ferrer I, Ecker JR, Esteller M.
Journal: Transl Psychiatry. 2016 Jan 19;6:e718. doi: 10.1038/tp.2015.214.
PMID: 26784972 – this article is OPEN ACCESS if you would like to read it.
The researchers were curious to look for common genetic markers between the major neurodegenerative disease. It is often forgotten that the different neurodegenerative conditions, such as Alzheimer’s disease and Parkinson’s disease, share some common pathological features (the characteristic signs of the diseases in the brain).
For example, when you look at the brains of people with Alzheimer’s disease, approximately 50% of them will also have the alpha-synuclein-containing ‘Lewy bodies’ in their brains, which are more commonly associated with Parkinson’s disease. Likewise, Beta-amyloid plaques and neurotangles, which are characteristic features of Alzheimer’s disease are commonly found in Parkinson’s disease brains (click here and click here for more on this topic).
To find these shared genetic markers, the researcher extracted DNA from the prefrontal cortex (Brodmann area 9) of the brains of people with Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease and Alzheimer-like neurodegenerative profile associated with Down’s syndrome samples (more than 75 percent of people with Down Syndrome aged 65 and older develop Alzheimer’s disease – click here for more on this).
Importantly, the researchers were looking at DNA methylation, which is a commonly used tool that allows a cell to fix genes in the “off” position. That is to say, the gene can not be activated. Thus the researchers were looking for regions of DNA that have to closed down.
They found that a very defined set of genes are turned off in these neurodegenerative disorders, suggesting that these condition might have similar underlying mechanisms or processes that subsequently develop into different clinical entities. These newly identified regions of DNA methylation will be further investigated with the goal that one day they may be used as biomarkers in diagnosis and also as potential new targets for the regenerative therapies.