Tag: gene

A tête-à-tête about TET2

~ Simon ~ 3 Comments

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Epigenetics is the study of how non-genetic factors affect genetics. It explores the influence of lifestyle or environmental factors on the activity surrounding our DNA.

Recently researchers have been investigating epigenetics within the context of Parkinson’s, and they have discovered a “master switch” that could represent an important target for future therapeutic treatments for the condition.

The research focuses on a protein called TET2.

In today’s post, we will discuss what epigenetics means, review the new research, and consider what the implications of these new findings could be.

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Not the same. Source: AutismBlog.

Identifical twin studies have been extremely useful to our understanding of conditions like Parkinson’s (Click here to read a previous SoPD post on twins research in Parkinson’s)

But the funny thing about identical twins is that in 100% of cases they aren’t identical.

Yeah sure, they initially share exactly the same DNA, but the further they get away from that magically moment of conception, the less alike they are.

Same DNA, subtle differences. Source: National Geographic

And we’re not talking about personality or likes/dislikes here.

As biological organisms twins diverge significantly after conception and as the age through life. But if they share the same DNA – the same genetic blueprint – how are these difference possible?

The answer to this question may lie in epigenetics.

What is epigenetics?

Continue reading “A tête-à-tête about TET2” →

Novartis focuses on improving PARKIN control

~ Simon ~ 8 Comments

Last week, as everyone was preparing for Christmas celebrations, researchers at the pharmaceutic company Novartis published new research on a gene that is involved with Parkinson’s, called PARKIN (or PARK2).

They used a new gene editing technology – called CRISPR – to conduct a large screening study to identify proteins that are involved with the activation of PARKIN.

In today’s post we will look at what PARKIN does, review the research report, and discuss how these results could be very beneficial for the Parkinson’s community.

Source: Novartis

As many people within the Parkinson’s community will be aware, 2017 represented the 200th anniversary of the first report of Parkinson’s disease by James Parkinson.

It also the 20th anniversary of the discovery of first genetic mutation (or variant) that increases the risk of developing Parkinson’s. That genetic variation occurs in a region of DNA (a gene) called ‘alpha synuclein’. Yes, that same alpha synuclein that seems to play such a critical role in Parkinson’s (Click here to read more about the 20th anniversary).

In 2018, we will be observing the 20th anniversary of the second genetic variation associated with Parkinson.

That gene is called PARKIN:

Title: Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
Authors: Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N
Journal: Nature. 1998 Apr 9; 392(6676):605-8
PMID: 9560156

In 1998, Japanese researchers published this report based on 5 individuals from 4 Japanese families who were affected by juvenile-onset Parkinson’s. In family 1, the affected individual was a female, 43 years old, born of first-cousin parents, and her two younger brothers are healthy. Her condition was diagnosed in her teens and it had then progressed very slowly afterwards. Her response to L-dopa was very positive, but L-dopa-induced dyskinesia were frequent. In family 2-4, affected individuals (born to unrelated parents) exhibited very similar clinical features to the subject in family 1. The age of onset was between 18 to 27 years of age.

Using previous research and various techniques the investigators were able to isolate genetic variations that were shared between the 5 affected individuals. They ultimately narrowed down their search to a section of DNA containing 2,960 base pairs, which encoded a protein of 465 amino acids.

They decided to call that protein PARKIN.

PARKIN Protein. Source: Wikipedia

How much of Parkinson’s is genetic?

Continue reading “Novartis focuses on improving PARKIN control” →

Non-invasive gene therapy: “You never monkey with the truth”

~ Simon ~ 5 Comments

Gene therapy involves treating medical conditions at the level of DNA – that is, altering or enhancing the genetic code inside cells to provide therapeutic benefits rather than simply administering drugs. Usually this approach utilises specially engineered viruses to deliver the new DNA to particular cells in the body.

For Parkinson’s, gene therapy techniques have all involved direct injections of these engineered viruses into the brain – a procedure that requires brain surgery. This year, however, we have seen the EXTREMELY rapid development of a non-invasive approach to gene therapy for neurological condition, which could ultimately see viruses being injected in the arm and then travelling up to the brain where they will infect just the desired population of cells.

Last week, however, this approach hit a rather significant obstacle.

In today’s post, we will have a look at this gene therapy technology and review the new research that may slow down efforts to use this approach to help to cure Parkinson’s.

Gene therapy. Source: rdmag

When you get sick, the usual solution is to visit your doctor.

They will prescribe a medication for you to take, and then all things going well (fingers crossed/knock on wood) you will start to feel better. It is a rather simple and straight forward process, and it has largely worked well for most of us for quite some time.

As the overall population has started to live longer, however, we have begun to see more and more chronic conditions which require long-term treatment regimes. The “long-term” aspect of this means that some people are regularly taking medication as part of their daily lives. In many cases, these medications are taken multiple times per day.

A good example of this is Levodopa (also known as Sinemet or Madopar) which is the most common treatment for the chronic condition of Parkinson’s disease.

When you swallow your Levodopa pill, it is broken down in the gut, absorbed through the wall of the intestines, transported to the brain via our blood system, where it is converted into the chemical dopamine – the chemical that is lost in Parkinson’s disease. This conversion of Levodopa increases the levels of dopamine in your brain, which helps to alleviate the motor issues associated with Parkinson’s disease.

7001127301-6010801

Levodopa. Source: Drugs

This pill form of treating a disease is only a temporary solution though. People with Parkinson’s – like other chronic conditions – need to take multiple tablets of Levodopa every day to keep their motor features under control. And long term this approach can result in other complications, such as Levodopa-induced dyskinesias in the case of Parkinson’s.

Yeah, but is there a better approach?

Continue reading “Non-invasive gene therapy: “You never monkey with the truth”” →

Beware of the PINK-SNO(W) man!

~ Simon ~ 3 Comments

There is a protein in most of the cells in your body called “PTEN-induced putative kinase 1″ (or simply PINK1). It plays an important role in keeping your cells healthy.

Genetic variations in the PINK1 gene have been shown to increase ones risk of developing Parkinson’s. 

This week researchers have identified a method by which the function of the PINK1 protein can be inhibited and this results in increased vulnerability to Parkinson’s. In this post, we will look at what PINK1 does, how it is inhibited, and what this could mean for the Parkinson’s community.

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Mitochondria (green) in health cells (left) and in unhealthy cells (right).
The nucleus of the cell is in blue. Source: Salk Institute

I have previously spoken a lot about mitochondria and Parkinson’s on this website.

For the uninitiated, mitochondria are the power house of each cell. They help to keep the lights on. Without them, the party is over and the cell dies.

Mitochondria

Mitochondria and their location in the cell. Source: NCBI

You may remember from high school biology class that mitochondria are tiny bean-shaped objects within the cell. They convert nutrients from food into Adenosine Triphosphate (or ATP). ATP is the fuel which cells run on. Given their critical role in energy supply, mitochondria are plentiful (some cells have thousands) and highly organised within the cell, being moved around to wherever they are needed.

Like you and I and all other things in life, however, mitochondria have a use-by date.

As mitochondria get old and worn out (or damaged) with time, the cell will recycle them via a process called mitophagy (a blending of the words mitochondria and autophagy which is the waste disposal system of each cell).

What does this have to do with Parkinson’s disease?

Continue reading “Beware of the PINK-SNO(W) man!” →

We need a clinical trial of broccoli. Seriously!

~ Simon ~ 6 Comments

In a recent post, I discussed research looking at foods that can influence the progression of Parkinson’s (see that post here). I am regularly asked about the topic of food and will endeavour to highlight more research along this line in future post.

In accordance with that statement, today we are going to discuss Cruciferous vegetables, and why we need a clinical trial of broccoli.

I’m not kidding.

There is growing research that a key component of broccoli and other cruciferous vegetables – called Glucoraphanin – could have beneficial effects on Parkinson’s disease. In today’s post, we will discuss what Glucoraphanin is, look at the research that has been conducted and consider why a clinical trial of broccoli would be a good thing for Parkinson’s disease.

 

Cruciferous vegetables. Source: Diagnosisdiet

Like most kids, when I was young I hated broccoli.

Man, I hated it. With such a passion!

Usually they were boiled or steamed to the point at which they have little or no nutritional value, and they largely became mush upon contact with my fork.

The stuff of my childhood nightmares. Source: Modernpaleo

As I have matured (my wife might debate that statement), my opinion has changed and I have come to appreciate broccoli. Our relationship has definitely improved.

In fact, I have developed a deep appreciation for all cruciferous vegetables.

And yeah, I know what you are going to ask:

What are cruciferous vegetables?

Cruciferous vegetables are vegetables of the Brassicaceae family (also called Cruciferae). They are a family of flowering plants commonly known as the mustards, the crucifers, or simply the cabbage family. They include cauliflower, cabbage, garden cress, bok choy, broccoli, brussels sprouts and similar green leaf vegetables.

Cruciferous vegetables. Source: Thetherapyshare

So what have Cruciferous vegetables got to do with Parkinson’s?

Well, it’s not the vegetables as such that are important. Rather, it is a particular chemical that this family of plants share – called Glucoraphanin – that is key.

What is Glucoraphanin?

Continue reading “We need a clinical trial of broccoli. Seriously!” →

Voyager Therapeutics: phase Ib clinical trial results

~ Simon ~ 15 Comments

 

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.

Source: Joshworth

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).

Continue reading “Voyager Therapeutics: phase Ib clinical trial results” →

Future of gene therapy: hAAVing amazing new tools

~ Simon ~ 5 Comments

image-20151106-16253-1rzjd0s

In this post I review recently published research describing interesting new gene therapy tools.

“Gene therapy” involved using genetics, rather than medication to treat conditions like Parkinson’s disease. By replacing faulty sections of DNA (or genes) or providing supportive genes, doctors hope to better treat certain diseases.

While we have ample knowledge regarding how to correct or insert genes effectively, the problem has always been delivery: getting the new DNA into the right types of cells while avoiding all of the other cells.

Now, researchers at the California Institute of Technology may be on the verge of solving this issue with specially engineered viruses.

gene_therapy_augmentation_yourgenome

Gene therapy. Source: yourgenome

When you get sick, the usual solution is to visit your doctor. They will prescribe a medication for you to take, and then all things going well (fingers crossed/knock on wood) you will start to feel better. It is a rather simple and straight forward process, and it has largely worked well for most of us for quite some time.

As the overall population has started to live longer, however, we have become more and more exposed to chronic conditions which require long-term treatment regimes. The “long-term” aspect of this means that some people are regularly taking medication as part of their daily lives. In many cases, these medications are taken multiple times per day.

An example of this is Levodopa (also known as Sinemet or Madopar) which is the most common treatment for the chronic condition of Parkinson’s disease. When you swallow your Levodopa pill, it is broken down in the gut, absorbed through the wall of the intestines, transported to the brain via our blood system, where it is converted into the chemical dopamine – the chemical that is lost in Parkinson’s disease. This conversion of Levodopa increases the levels of dopamine in your brain, which helps to alleviate the motor issues associated with Parkinson’s disease.

7001127301-6010801

Levodopa. Source: Drugs

This pill form of treating a disease is only a temporary solution though. People with Parkinson’s disease – like other chronic conditions – need to take multiple tablets of Levodopa every day to keep their motor features under control. And long term this approach can result in other complications, such as Levodopa-induced dyskinesias in the case of Parkinson’s.

Yeah, but is there a better approach?

Some researchers believe there is. But we are not quite there yet with the application of that approach. Let me explain:

Continue reading “Future of gene therapy: hAAVing amazing new tools” →

Tetrabenazine: A strategy for Levodopa-induced dyskinesia?

~ Simon ~ 7 Comments

Dyk

For many people diagnosed with Parkinson’s disease, one of the scariest prospects of the condition that they face is the possibility of developing dyskinesias.

Dyskinesias are involuntary movements that can develop after long term use of the primary treatment of Parkinson’s disease: Levodopa

In todays post I discuss one experimental strategy for dealing with this debilitating aspect of Parkinson’s disease.

Dysco

Dyskinesia. Source: JAMA Neurology

There is a normal course of events with Parkinson’s disease (and yes, I am grossly generalising here).

First comes the shock of the diagnosis.

This is generally followed by the roller coaster of various emotions (including disbelief, sadness, anger, denial).

Then comes the period during which one will try to familiarise oneself with the condition (reading books, searching online, joining Facebook groups), and this usually leads to awareness of some of the realities of the condition.

One of those realities (especially for people with early onset Parkinson’s disease) are dyskinesias.

What are dyskinesias?

Dyskinesias (from Greek: dys – abnormal; and kinēsis – motion, movement) are simply a category of movement disorders that are characterised by involuntary muscle movements. And they are certainly not specific to Parkinson’s disease.

As I have suggested in the summary at the top, they are associated in Parkinson’s disease with long-term use of Levodopa (also known as Sinemet or Madopar).

7001127301-6010801

Sinemet is Levodopa. Source: Drugs

Continue reading “Tetrabenazine: A strategy for Levodopa-induced dyskinesia?” →

The omnigenics of Parkinson’s disease?

~ Simon ~ 6 Comments

agarose-gel-electrophoresis-dna

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.

shutterstock_225119212

Source: Discover

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):

Nature
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.
PMID: 28146470

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.

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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.

Continue reading “The omnigenics of Parkinson’s disease?” →