They say that “we are what we eat”, and food can certainly have a major impact on health and wellbeing.
Recently, a research report has been published that looks into the topic of food in the context of Parkinson’s disease.
And the results are interesting.
In today’s post we will outline the new research, discuss the results, and what they mean for people living with Parkinson’s disease.
Seattle. Source: Wikipedia
Established in 1978, Bastyr University is an alternative medicines institute.
The original campus (Bastyr now has a second campus in San Diego, California) is tucked into the idyllic forested area of Saint Edward State Park on the edge of Lake Washington, just north-east of downtown Seattle (Washington).
Hang on a moment – ‘alternative medicines’?
While I can understand that some readers may immediately question why ‘alternative medicines’ are being mentioned on the “Science” of Parkinson’s disease website, here at the SoPD HQ we entertain any and all ideas with regards to Parkinson’s disease. And we are certainly open to any data that may be of interest to the Parkinson’s community.
Particularly, when that data comes from this individual:
This is Dr Laurie Mischley. She’s awesome.
She is an Associate Clinical Investigator at Bastyr University, a guru when it comes to nutrition, and our first port of call when we field questions regarding Parkinson’s disease and diet. You can see her in action in this video (recommended viewing for those with Parkinson’s disease and interested in the topic of diet/nutrition):
Importantly, Dr Mischley is also responsible for most of the clinical study data that we have on Acetylcysteine (also known as N-acetylcysteine or simply NAC) in Parkinson’s disease (Click here to read more about this).
And she is currently co-ordinating the “Complementary & Alternative Medicine Care in Parkinson’s Disease” (CAM Care in PD) study, which is attempting to ‘collect as much data as possible over a five-year period with the hope of finding dietary and lifestyle factors associated with a slower disease progression’. The study is still recruiting and I would encourage readers to take time to enrol in the study and fill in the survey (Click here to learn more).
This ongoing CAM study (and Dr Mischley’s efforts) has recently borne fruit that will be of real interest to the Parkinson’s community. It is a research report that reviews dietary and nutritional supplemental factors that can impact Parkinson’s disease progression.
This is the study here:
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.
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?
It is particularly useful for groups like the Parkinson’s community though, who are tired of having just one hour per year of assessments with their neurologist.
In today’s post, we will look at some new tracking/monitoring technologies that are being developed that could have important implications for not only how we assess Parkinson’s disease, but also for how we treat it.
Homo deus. Source: RealClearLife
I have recently finished reading ‘Homo Deus‘ by Yuval Noah Harari – the excellent follow-up to his previous book ‘Sapiens‘ (which is an absolute MUST READ!). The more recent book provides an utterly fascinating explanation of how we have come to be where we will be in the future (if that makes any sense).
In the final few chapters, Harari discusses many of the technologies that are currently under development which will change the world we live in (with a lot of interesting and cautionary sections on artificial intelligence – the machines that will know vastly more about us than we know about ourselves).
Of particular interest in this part of the book was a section on the Google-Novartis smart lens.
What is the Google-Novartis smart lens?
The initial project is rather ambitious: develop and take to the clinic a glucose-sensing contact lens for people with diabetes. The idea has been particularly championed by Google founder Sergey Brin (a prominent figure within the Parkinson’s community with his significant contributions to Parkinson’s research each year).
People with diabetes have to keep pricking their finger over the course of a day in order to check the levels of insulin in their blood. A less laborious approach would be welcomed by the diabetic world (an estimated 415 million people living with diabetes in the world).
This is what the lens may eventually look like:
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.
Last year – two years after actor Robin Williams died – his wife Susan Schneider Williams wrote an essay entitled The terrorist inside my husband’s head, published in the journal Neurology.
It is a heartfelt/heartbreaking insight into the actor’s final years. It also highlights the plight of many who are diagnosed with Parkinson’s disease, but experience an array of additional symptoms that leave them feeling that something else is actually wrong.
Today’s post is all about Dementia with Lewy bodies (or DLB). In particular, we will review the latest refinements and recommendations of the Dementia with Lewy Bodies Consortium, regarding the clinical and pathologic diagnosis of DLB.
Robin Williams. Source: Quotesgram
On the 28th May of 2014, the actor Robin Williams was diagnosed with Parkinson’s disease.
At the time, he had a slight tremor in his left hand, a slow shuffling gait and mask-like face – some of the classical features of Parkinson’s disease.
According to his wife, the diagnosis gave the symptoms Robin had been experiencing a name. And this brought her a sense of relief and comfort. Now they could do something about the problem. Better to know what you are dealing with rather than be left unsure and asking questions.
But Mr Williams sensed that something else was wrong, and he was left unsure and asking questions. While filming the movie Night at the Museum 3, Williams experienced panic attacks and regularly forgot his lines. He kept asking the doctors “Do I have Alzheimer’s? Dementia? Am I schizophrenic?”
Williams took his own life on the 11th August 2014, and the world mourned the tragic loss of a uniquely talented performer.
When the autopsy report came back from the coroner, however, it indicated that the actor had been misdiagnosed.
He didn’t have Parkinson’s disease.
What he actually had was Dementia with Lewy bodies (or DLB).
What is Dementia with Lewy bodies?
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.
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:
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.
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.
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.
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:
The title of today’s post is written in jest – my job as a researcher scientist is to find a cure for Parkinson’s disease…which will ultimately make my job redundant! But all joking aside, today was a REALLY good day for the Parkinson’s community.
Last night (3rd August) at 23:30, a research report outlining the results of the Exenatide Phase II clinical trial for Parkinson’s disease was published on the Lancet website.
And the results of the study are good:while the motor symptoms of Parkinson’s disease subject taking the placebo drug proceeded to get worse over the study, the Exenatide treated individuals did not.
The study represents an important step forward for Parkinson’s disease research. In today’s post we will discuss what Exenatide is, what the results of the trial actually say, and where things go from here.
Last night, the results of the Phase II clinical trial of Exenatide in Parkinson’s disease were published on the Lancet website. In the study, 62 people with Parkinson’s disease (average time since diagnosis was approximately 6 years) were randomly assigned to one of two groups, Exenatide or placebo (32 and 30 people, respectively). The participants were given their treatment once per week for 48 weeks (in addition to their usual medication) and then followed for another 12-weeks without Exenatide (or placebo) in what is called a ‘washout period’. Neither the participants nor the researchers knew who was receiving which treatment.
At the trial was completed (60 weeks post baseline), the off-medication motor scores (as measured by MDS-UPDRS) had improved by 1·0 points in the Exenatide group and worsened by 2·1 points in the placebo group, providing a statistically significant result (p=0·0318). As you can see in the graph below, placebo group increased their UPDRS motor score over time (indicating a worsening of motor symptoms), while Exenatide group (the blue bar) demonstrated improvements (or a lowering of motor score).
Reduction in motor scores in Exenatide group. Source: Lancet
This is a tremendous result for Prof Thomas Foltynie and his team at University College London Institute of Neurology, and for the Michael J Fox Foundation for Parkinson’s Research who funded the trial. Not only do the results lay down the foundations for a novel range of future treatments for Parkinson’s disease, but they also validate the repurposing of clinically available drug for this condition.
In this post we will review what we know thus far. And to do that, let’s start at the very beginning with the obvious question:
So what is Exenatide?
In Silicon valley (California), everyone is always looking for the “next killer app” – the piece of software (or application) that is going to change the world. The revolutionary next step that will solve all of our problems.
The title of today’s post is a play on the words ‘killer app’, but the ‘app’ part doesn’t refer to the word application. Rather it relates to the Alzheimer’s disease-related protein Amyloid Precursor Protein (or APP). Recently new research has been published suggesting that APP is interacting with a Parkinson’s disease-related protein called Leucine-rich repeat kinase 2 (or LRRK2).
The outcome of that interaction can have negative consequences though.
In today’s post we will discuss what is known about both proteins, what the new research suggests and what it could mean for Parkinson’s disease.
Seattle. Source: Thousandwonders
In the mid 1980’s James Leverenz and Mark Sumi of the University of Washington School of Medicine (Seattle) made a curious observation.
After noting the high number of people with Alzheimer’s disease that often displayed some of the clinical features of Parkinson’s disease, they decided to examined the postmortem brains of 40 people who had passed away with pathologically confirmed Alzheimer’s disease – that is, an analysis of their brains confirmed that they had Alzheimer’s.
What the two researchers found shocked them:
Title: Parkinson’s disease in patients with Alzheimer’s disease.
Authors: Leverenz J, Sumi SM.
Journal: Arch Neurol. 1986 Jul;43(7):662-4.
Of the 40 Alzheimer’s disease brains that they looked at nearly half of them (18 cases) had either dopamine cell loss or Lewy bodies – the characteristic features of Parkinsonian brain – in a region called the substantia nigra (where the dopamine neurons are located). They next went back and reviewed the clinical records of these cases and found that rigidity, with or without tremor, had been reported in 13 of those patients. According to their analysis 11 of those patients had the pathologic changes that warranted a diagnosis of Parkinson’s disease.
And the most surprising aspect of this research report: Almost all of the follow up studies, conducted by independent investigators found exactly the same thing!
It is now generally agreed by neuropathologists (the folks who analyse sections of brain for a living) that 20% to 50% of cases of Alzheimer’s disease have the characteristic round, cellular inclusions that we call Lewy bodies which are typically associated with Parkinson disease. In fact, in one analysis of 145 Alzheimer’s brains, 88 (that is 60%!) had chemically verified Lewy bodies (Click here to read more about that study).
A lewy body (brown with a black arrow) inside a cell. Source: Cure Dementia
Oh, and if you are wondering whether this is just a one way street, the answer is “No sir, this phenomenon works both ways”: the features of the Alzheimer’s brain (such as the clustering of a protein called beta-amyloid) are also found in many cases of pathologically confirmed Parkinson’s disease (Click here and here to read more about this).
So what are you saying? Alzheimer’s and Parkinson’s disease are the same thing???
In October 2015, researchers from Georgetown University announced the results of a small clinical trial that got the Parkinson’s community very excited. The study involved a cancer drug called Nilotinib, and the results were rather spectacular.
What happened next, however, was a bizarre sequence of disagreements over exactly what should happen next and who should be taking the drug forward. This caused delays to subsequent clinical trials and confusion for the entire Parkinson’s community who were so keenly awaiting fresh news about the drug.
Earlier this year, Georgetown University announced their own follow up phase II clinical trial and this week a second phase II clinical trial funded by a group led by the Michael J Fox foundation was initiated.
In todays post we will look at what Nilotinib is, how it apparently works for Parkinson’s disease, what is planned with the new trial, and how it differs from the ongoing Georgetown Phase II trial.
The FDA. Source: Vaporb2b
This week the U.S. Food and Drug Administration (FDA) has given approval for a multi-centre, double-blind, randomised, placebo-controlled Phase IIa clinical trial to be conducted, testing the safety and tolerability of Nilotinib (Tasigna) in Parkinson’s disease.
This is exciting and welcomed news.
What is Nilotinib?
Nilotinib (pronounced ‘nil-ot-in-ib’ and also known by its brand name Tasigna) is a small-molecule tyrosine kinase inhibitor, that has been approved for the treatment of imatinib-resistant chronic myelogenous leukemia (CML).
What does any that mean?
Basically, it is the drug that is used to treat a type of blood cancer (leukemia) when the other drugs have failed. It was approved for treating this cancer by the FDA in 2007.