We have previously discussed the powerful antioxidant Resveratrol, and reviewed the research suggesting that it could be beneficial in the context of Parkinson’s disease (Click here to read that post).
I have subsequently been asked by several readers to provide a critique of the Parkinson’s-associated research focused on Resveratrol’s twin sister, Pterostilbene (pronounced ‘Terra-still-bean’).
But quite frankly, I can’t.
Why? Because there is NO peer-reviewed scientific research on Pterostilbene in models of Parkinson’s disease.
In today’s post we will look at what Pterostilbene is, what is known about it, and why we should seriously consider doing some research on this compound (and its cousin Piceatannol) in the context of Parkinson’s disease.
Blue berries are the best natural source of Pterostilbene. Source: Pennington
So this is likely to be the shortest post in SoPD history.
Because there is nothing to talk about.
There is simply no Parkinson’s-related research on the topic of today’s post: Pterostilbene. And that is actually a crying shame, because it is a very interesting compound.
What is Pterostilbene?
Like Resveratrol, Pterostilbene is a stilbenoid.
Stilbenoids are a large class of compounds that share the basic chemical structure of C6-C2-C6:
Resveratrol is a good example of a stilbenoid. Source: Wikipedia
Stilbenoids are phytoalexins (think: plant antibiotics) produced naturally by numerous plants. They are small compounds that become active when the plant is under attack by pathogens, such as bacteria or fungi. Thus, their function is generally considered to part of an anti-microbial/anti-bacterial plant defence system for plants.
The most well-known stilbenoid is resveratrol which grabbed the attention of the research community in a 1997 study when it was found to inhibit tumour growth in particular animal models of cancer:
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?
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).
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.
This is one of the first immuno-therapies being tested in Parkinson’s disease, and the results indicate that the treatment was active and well tolerated.
In this post we will review the press release and what it tells us regarding this clinical trial.
Antibodies binding to proteins. Source: AXS
When your body is infected by a foreign agent, it begins to produce some things called antibodies. In most cases, these are Y-shaped proteins that binds to the un-wanted invader and act as a beacon for the immune system. It is a very effective system, allowing us to go about our daily business without getting sick on a regular basis. Antibodies allow us to build up immunity, or resistance of an organism to infection or disease.
Scientist have harnessed the power of this natural process, and they have use it to develop methods of helping our bodies fight off disease.
The first approach is called Acquired Immunity (or adaptive immunity), and it is based on the idea that exposure of the immune system to a pathogen (disease/damage causing agent) creates an ‘immunological memory’ within our immune system, and this leads to an enhanced response to subsequent future encounters with that same pathogen.
Scientists have used the idea of acquired immunity to develop what we call vaccines – which are simply small, neutral fragments of specific pathogen that help the immune system to build up immunity (or resistance) before the body is attacked by the disease-causing pathogen itself.
Vaccination. Source: WebMD
The second approach is called Passive Immunity.
Passive immunisation is simply the sharing of antibodies. And that might sound a bit disturbing, but it is actually a naturally occurring process. For example, a mother’s antibodies are transferred to her baby in the womb via the placenta.
And again, scientists have devised ways of producing passive immunisation artificially. And recently researchers have been using this approach to attack many medical conditions (particularly cancer), in an area of medicine called immunotherapy.
Think of it as simply boosting the immune system by supplementing the supply of antibodies. Scientists can produce high levels of antibodies that specifically target a particular pathogen and then transfer those antibodies to affected people via an intravenous injection.
How is this being used for Parkinson’s disease?
Well, we have previously discussed the idea of a vaccine for Parkinson’s disease (click here to read that post), and we have been closely following the progress of an Austrian company, AffiRis, who are leading the vaccination approach (Click here for that post).
The vaccine approach is targeting the Parkinson’s disease associated protein, Alpha synuclein. It is believed that a bad kind of alpha synuclein is causing the spread of the condition, by being passed from cell to cell. The goal of the vaccine is to capture and remove all of the alpha synuclein being passed between cells and thus (hopefully) halt the progress of – or at least slow down – the disease.
And this week, another company – Prothena – has reported the results of their phase 1 trial for a passive immunity approach to Parkinson’s disease. They have been injecting subjects in the trial with a treatment called PRX002.
(Remember that a phase 1 trial simply tests the safety of a treatment in humans, it is not required to test efficacy of the treatment. Efficacy comes with phases 2 & 3 trials)
What is PRX002?
PRX002 is a monoclonal antibody. The scientists at the biotech company Prothena have artificially produced large amounts of antibodies to alpha synuclein and these have been injected into people with Parkinson’s disease.
Monoclonal antibodies. Source: Astrazeneca
Prothena provide a short video explaining this concept (click here to view the video).
So what were the results of the Prothena study?
The study was conducted in collaboration the pharmaceutical company Roche. It was a double-blind (so both the researchers and subjects did not know what they were receiving until the conclusion of the study), placebo-controlled study involving 80 people with Parkinson’s disease. The subjects were randomly assigned to one of six groups, which received either PRX002 or a placebo. There were six doses of PRX002 tested in the study (0.3, 1, 3, 10, 30 or 60 mg/kg).
The study was conducted over six-month, during which patients received three once-a-month injections of either PRX002 or placebo. The subjects were then followed for an observational period of three months.
According to the press release, no serious treatment-related adverse events were reported in PRX002 treated patients. Mild treatment-related adverse events (greater than anything experienced within the placebo group) were noted in 4 of the 12 subjects in the highest dosage group of PRX002, including constipation and diarrhoea.
Importantly, the investigators reported that thePRX002 antibodies were crossing the blood brain barrier and entering the brain. This resulted in a rapid reduction of alpha-synuclein levels (in some cases by up to 97 percent after a single dose!).
The follow-on Phase 2 clinical study is expected to begin in 2017.
What is the difference between the vaccine and the passive immunity approaches?
Basically, it comes down to levels of control. With a vaccination, once you have injected the vaccine and the immune system is activated, there isn’t much you can do to control the response of the body. And that immune memory is going to last a long time. The passive immunity response, on the other hand, requires regular injections of antibodies which can be stopped if adverse effects are noted.
Plus – and forgive me if I sound a little bit cynical here – drug companies prefer a regular treatment approach (which they can charge for each visit) compared to a one-shot cure. It’s simply a better business model.
What happens next?
In both cases – the vaccine and the passive immunity approaches – phase 2 trials are being set up by the respective companies and we will wait to see have affective these treatments are at slowing down Parkinson’s disease.
If they are affective, expect big headlines in the media and plans for adults everywhere to start being vaccinated. If they fail,…. well, we will have to re-address our understanding of the role of alpha synuclein in Parkinson’s disease.
Interesting times lie ahead.
The banner for todays post was sourced from Prothena