Tag: disease

O’mice an’ men – gang aft agley

~ Simon ~ 16 Comments

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
PMID: 28882997

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?

Continue reading “O’mice an’ men – gang aft agley” →

QUATS going on?!?

~ Simon ~ 8 Comments

BE WARNED: THIS POST MIGHT UPSET SOME READERS

A recently published research report has caused a bit of a fuss in the media, and I have been contacted by a lot of concerned readers regarding this particular study.

It deals with some chemicals – which can be found in everyday products – that may be having a negative effect on biological processes that are related to Parkinson’s disease – specifically, the normal functioning of the mitochondria (the power stations of each cell).

In today’s post we will discuss the new research, what the chemicals do, and whether the Parkinson’s community should be concerned.

Source: Sacramentodentistry

Toothpaste.

It is something that most of us take completely for granted in the modern world. A product that sits in our bathroom, by the sink or on a shelf, and 2-3 times per day we stick some of it in our mouth and brush it around a bit. Given the well ingrained habit of repetitively ingesting of the stuff, we have little trouble with the idea of switching brands or trying new variations (“Oooh look, this one will make your teeth whiter. Let’s try it”).

I mean, come on – it’s just toothpaste. It’s safe, right?

It probably won’t surprise many of you to learn that the composition of toothpaste has changed quite a bit over the years, but what might amaze you is just how many years are involved with that statement: 

Egyptian toothbrush. Source: Nathanpaarth

The Egyptians recognised the importance of looking after one’s teeth at a very early stage. Apparently they had a lot of trouble with their teeth because their bread had grit in it which wore away their enamel. As far back as 5000BC, they had a form of toothpaste that they used to clean their teeth. It was a mix of powdered ashes of ox hooves, myrrh, powdered and burnt eggshells, and pumice (Source: Wikipedia). The Greeks, followed by the Romans, improved on the recipes (by adding abrasive ingredients such as crushed bones and oyster shells – delightful, huh?), but it wasn’t until after World War I that the modern day pre-mixed toothpastes became popular.

The cavity fighting chemical, Fluoride, was first added to toothpastes in the 1890s, and in 1908 Newell Sill Jenkins (an American dentist) invented the first toothpaste that contained disinfectants. It was called Kolynos (from the Greek words Kolyo nosos (κωλύω νόσος), meaning “disease prevention”). 

Source: Flickr

Following the advent of Kolynos, most toothpaste companies added antiseptic and disinfectant agents to improve the quality and effectiveness of their product. Being offered a tooth cleaning product with magical antibiotic properties seemed to reassure consumers that they were buying something that might actually work. And this led to more and more chemicals being added to toothpaste. Such additions included chemical like triclosan, cetylpyridinium chloride and benzalkonium chloride.

These chemicals are safe though…right?

Continue reading “QUATS going on?!?” →

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” →

Dear FDA, this is bigly wrong…and you know it!

~ Simon ~ 12 Comments

maxresdefault

Dopamine agonist treatments are associated with approximately 90% of hyper-sexuality and compulsive gambling cases that occur in people with Parkinson’s disease.

This issue does not affect everyone being treated with this class of drugs, but it is a problem that keeps popping up, with extremely damaging consequences for the affected people who gamble away their life’s saving or ruin their marriages/family life. 

The U.S. Food and Drug Administration (FDA) is yet to issue proper warning for this well recognised side-effect of dopamine agonists, and yet last week they gave clearance for the clinical testing of a new implantable device that will offer continuous delivery of dopamine agonist medication.

In today’s post, we will discuss what dopamine agonists are, the research regarding the impulsive behaviour associated with them, and why the healthcare regulators should acknowledge that there is a problem.

2000px-dopamine2-svg

Dopamine. Source: Wikimedia

Before we start talking about dopamine agonists, let’s start at the very beginning:

What is dopamine?

By the time a person is sitting in front of a neurologist and being told that they ‘have Parkinson’s disease’, they will have lost half the dopamine producing cells in an area of the brain called the midbrain.

Dopamine is a chemical is the brain that plays a role in many basic functions of the brain, such as motor co-ordination, reward, and memory. It works as a signalling molecule (or a neurotransmitter) – a way for brain cells to communicate with each other. Dopamine is released from brain cells that produce this chemical (not all brain cells do this), and it binds to target cells, initiating biological processes within those cells.

1471340161-dopamine-banner

Dopamine being released by one cell and binding to receptors on another. Source: Truelibido

Dopamine binds to target cells via five different receptors – that is to say, dopamine is released from one cell and can bind to one of five different receptors on the target cell (depending on which receptor is present). The receptor is analogous to a lock and dopamine is the key. When dopamine binds to a particular receptor it will allow something to happen in that cell. And this is how information from a dopamine neuron is passed or transmitted on to another cell.

dopamine-receptors-150803

Dopamine acts like a key. Source: JourneywithParkinsons

Continue reading “Dear FDA, this is bigly wrong…and you know it!” →

Hey DJ, I-so-sit-rate!

~ Simon ~ 3 Comments

The title of this post probably reads like the mad, drug-fuelled scream of a drunk Saturday night party animal, but the elements of it may be VERY important for a particular kind of Parkinson’s disease.

Mutations in a gene called DJ-1 can cause an early onset form of Parkinson’s disease. The protein of DJ-1 plays an important role in how cells handle oxidative stress – or the increase in damaging free radicals (explained below).

This week researchers announced that they have found an interesting new therapeutic target for people with DJ-1 associated Parkinson’s disease: A chemical called Isocitrate.

In this post, we will discuss what DJ-1 is involved with Parkinson’s disease, how isocitrate helps the situation, and what the results of new research mean for future therapeutic strategies.

original-26772-1364707371-8

Source: Listchallenge

In 2017, we are not only observing the 200 year anniversary of the first description of Parkinson’s disease (by one Mr James Parkinson), but also the 20th anniversary of the discovery of the first genetic variation associated with the condition (Click here to read more about that). Our understanding of the genetics of Parkinson’s disease since 1997, has revolutionised the way we look at Parkinson’s disease and opened new doors that have aided us in our understanding.

During the last 20 years, we have identified numerous sections of DNA (these regions are called genes) where small errors in the genetic coding (mutations or variants) can result in an increased risk of developing Parkinson’s disease. As the graph below indicates, mutations in some of these genes are very rare, but infer a very high risk, while others are quite common but have a low risk of Parkinson’s disease.

The genetics of PD. Source: Journal of Parkinson’s disease

Some of the genetic mutation need to be provided by both the parents for Parkinson’s to develop (an ‘autosomal recessive‘ mutation – the yellow circles in the graph above); while in other cases the genetic variant needs only to be provided by one of the parents (an ‘autosomal dominant’ mutation – the blue circles). Many of the genetic mutations are very common and simply considered a region of increased risk (green circles).

Importantly, all of these genes provide the instructions for making a protein – which are the functional parts in a cell. And each of these proteins have specific roles in biological processes. These functions tell us a little bit about how Parkinson’s disease may be working. Each of them is a piece of the jigsaw puzzle that we are trying to finish. As you can see in the image below, many of the genes mentioned in the graph above give rise to proteins that are involved in different parts of the process of autophagy – or the waste disposal system of the cell. You may notice that some proteins, like SCNA (otherwise known as alpha synuclein), are involved in multiple steps in this process.

The process of autophagy. Source: Nature

In today’s post we are going to look at new research regarding just one of these genes/proteins. It is called DJ-1, also known as Parkinson disease protein 7 (or PARK7).

What is DJ-1?

Continue reading “Hey DJ, I-so-sit-rate!” →

Lrrking in low orbit

~ Simon ~ 8 Comments

Last Monday, a SpaceX rocket lifted off from the Florida peninsular on route to the International Space Station.

On board that craft was an experiment that could have big implications for Parkinson’s disease. It involves a Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (or LRRK2).

In today’s post, we will discuss why we needed to send this protein into orbit.

The International Space Station. Source: NASA

When you look up at the sky tonight – if you look for long enough – you may well see a bright little object hurtling across the sky (Click here to learn more about how to track the International Space Station). Know that inside that bright little object passing over you there is currently some Parkinson’s disease-related research being conducted.

What is the International Space Station?

The International Space Station (or the ISS) is the largest human-made object that we have ever put into space. It is so big in fact that you can see it with the naked eye from Earth.

(How’s that for exciting viewing?)

The current space station is 73.3 metres (240 feet) long and 44.5 metres (146 feet) wide, weighing approximately 420 tonnes (924,740 lb), and it has been continuously occupied for 16 years and 289 days, making it the longest continuous human presence in low Earth orbit. The ISS travels at a speed of 7.67 km/second, maintains an altitude of between 330 and 435 km (205 and 270 mi), and completes 15.54 orbits per day (it has made over 102,000 orbits!).

The size of the the ISS compared to a Boeing Jumbo jet. Source: Reddit

First approved by President Ronald Reagan in 1984, it was not until November 1998 that the first components of the International space station were first launched into orbit. 36 shuttle flights were made to help build the station. The first crew members took up residence on the 2nd November 2000, and the station was completed in 2011. There is always 6 crew members on board – the current team are Expedition 52 – and it has been visited by 220 astronauts, cosmonauts and space tourists from 17 different nations since the project began.

Oh yeah, and if you want to see what it looks like on board the ISS, in 2015 the European Space Agency provided an interactive tour and earlier this year Google Maps added an interactive tour of the ISS.

Continue reading “Lrrking in low orbit” →

DPP-4: Not a Star Wars character

~ Simon ~ 9 Comments

Banner

Dipeptidyl peptidase-4 (or DPP-4) is an enzyme that breaks down the protein (GLP-1) that stimulates insulin release in your body. 

Inhibitors of DPP-4 are used in the treatment of Type 2 diabetes, because they help increase insulin levels in the body.

Recently some Swedish researchers noticed something curious about DPP-4 inhibitors: They appear to reduce the risk of developing Parkinson’s disease.

In today’s post, we will review what DPP-4 inhibitors do and look at how this could be reducing the risk of Parkinson’s disease.

januvia

Sitagliptin. Source: Diabetesmedicine

Last year an interesting research report about a class of medications that could possibly reduce the risk of developing Parkinson’s disease was published in the journal Movement disorders:

SWeds

Title: Reduced incidence of Parkinson’s disease after dipeptidyl peptidase-4 inhibitors-A nationwide case-control study.
Authors: Svenningsson P, Wirdefeldt K, Yin L, Fang F, Markaki I, Efendic S, Ludvigsson JF.
Journal: Movement Disorders 2016 Jul 19.
PMID: 27431803

In this study, the investigators used the Swedish Patient Register, to find the medical records of 980 people who were diagnosed with Parkinson’s disease but also had type 2 diabetes. Importantly, all of the subjects had been treated with Type 2 diabetes medication for at least 6 months prior to the date of Parkinson’s being diagnosed.

For comparative sake, they selected 5 controls (non-Parkinsonian) with Type 2 diabetes (n = 4,900) for each of their Parkinsonian+diabetes subjects. They next looked at whether GLP-1R agonists (such as Exenatide), Dipeptidyl peptidase-4 (or DPP-4) inhibitors, or any other oral Type 2 diabetic medication can influence the incidence of Parkinson’s disease.

Now, if all things are considered equal, then when looking at each diabetes medication there should be 1 person in the Parkinson’s disease + Type 2 diabetes for every 5 people in the Type 2 diabetes control group taking each medication right? That is because there are almost 1000 people in the first group and 5000 in the second group.

But this is not what the researchers found.

Continue reading “DPP-4: Not a Star Wars character” →

Exenatide: An editorial

~ Simon ~ 26 Comments

editorial

In my previous post, we briefly reviewed the results of the phase II double-blind, randomised clinical trial of Exenatide in Parkinson’s disease. The study indicates a statistically significant effect on motor symptom scores after being treated with the drug.

Over the last few days, there have been many discussions about the results, what they mean for the Parkinson’s community, and where things go from here, which have led to further questions.

In this post I would like to address several matters that have arisen which I did not discuss in the previous post, but that I believe are important.

bydureon

I found out about the Exenatide announcement – via whispers online – on the afternoon of the release. And it was in a mad rush when I got home that night that I wrote up the post explaining what Exenatide is. I published the post the following evening however because I could not access the research report from home (seriously guys, biggest finding in a long time and it’s not OPEN ACCESS?!?!?) and I had to wait until I got to work the next day to actually view the publication.

I was not really happy with the rushed effort though and decided to follow up that post. In addition, there has been A LOT of discussion about the results over the weekend and I thought it might be good to bring aspects of those different discussion together here. The individual topics are listed below, in no particular order of importance:

1. Size of the effect

There are two considerations here.

Firstly, there have been many comments about the actual size of the effect in the results of the study itself. When people have taken a deeper look at the findings, they have come back with questions regarding those findings.

And second, there have also been some comments about the size of the effect that this result has already had on the Parkinson’s community, which has been considerable (and possibly disproportionate to the actual result).

The size of the effect in the results

The results of the study suggested that Exenatide had a positive effect on the motor-related symptoms of Parkinson’s over the course of the 60 week trial. This is what the published report says, it is also what all of the media headlines have said, and it sounds really great right?

The main point folks keep raising, however, is that the actual size of the positive effect is limited to just the motor features of Parkinson’s disease. If one ignores the Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores and focuses on the secondary measures, there isn’t much to talk about. In fact, there were no statistically significant differences in any of the secondary outcome measures. These included:

Continue reading “Exenatide: An editorial” →

Higher socioeconomic status jobs

~ Simon ~ 11 Comments

o-INEQUALITY-GIF-facebook

People with high socioeconomic status jobs are believed to be better off in life.

New research published last week by the Centre for Disease Control, however, suggests that this may not be the case with regards to one’s risk of developing Parkinson’s disease.

In today’s post we will review the research and discuss what it means for our understanding of Parkinson’s disease.

childrenoflo

The impact of socioeconomic status. Source: Medicalxpress

In 2013, a group of researchers at Carnegie Mellon University found a rather astonishing but very interesting association:

Children from lower socioeconomic status have shorter telomeres as adults.

Strange, right?

Yeah, wow, strange… sorry, but what are telomeres?

Do you remember how all of your DNA is wound up tightly into 23 pairs of chromosomes? Well, telomeres are at the very ends of each of those chromosomes. They are literally the cap on each end. The name is derived from the Greek words ‘telos‘ meaning “end”, and ‘merοs‘ meaning “part”.

Telomeres are regions of repetitive nucleotide sequences (think the As, Gs, Ts, & Cs that make up your DNA) at each end of a chromosome. Their purpose seems to involve protecting the end of each chromosome from deteriorating or fusing with neighbouring chromosomes. Researchers also use their length is a marker of ageing because every time a cell divides, the telomeres on each chromosome gradually get shorter.

Continue reading “Higher socioeconomic status jobs” →

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?” →