Regular readers will be aware that here at the SoPD, we are on a mission to change the way we clinically test drugs (Click here for the most recent rant on this topic).
We have a lot of interesting drugs waiting in the pipeline to be clinically tested and an eager (read: desperate) population of individuals affected by Parkinson’s, but we are missing one critical part of the equation: better tools of assessment.
How can we determine whether a drug is actually working or not? And how can we better monitor people over time on said drug?
Our current methods assessing individuals with Parkinson’s rely heavily on clinical rating scales and brain imaging. These are basic tools at best, conducted episodically (annually in general, or once every 2-6 months during a clinical trial), and provide little in the way of useful objective data (on an individual basis).
In today’s post, we will look at a single aspect of Parkinson’s – sleep – and try to nut-out a better/more informative method of assessing it over time.
The Bluesky project. Source: Mirror
Last week tech industry giants Pfizer and IBM made an big announcement.
It was news that I have been quietly waiting to hear for some time.
It related to their “BlueSky Project” – a collaboration between the two companies to provide better methods of assessment/monitoring of Parkinson’s.
The two companies announced that they are now ready to start accepting the first participants for a new clinical trial.
And it is a really intriguing study for one simple reason:
The entire trial will take place inside one house.
This week Austrian biotech firm, AFFiRiS AG, made an announcement regarding their experimental immunotherapy/’vaccine’ approach for Parkinson’s.
In their press release, the company provided the results of a long-term Phase I clinical trial testing the tolerability and safety of their treatment AFFITOPE® PD01A.
The treatment was found to be safe and well-tolerated in people with Parkinson’s. But there was one sentence which was particularly intriguing in the press release regarding clinical symptoms.
In today’s post, we will discuss what is meant by ‘immunotherapy’, outline what this particular clinical trial involved, review the results, and explore what this could mean for the Parkinson’s community.
I have previously mentioned on this website that any ‘cure for Parkinson’s’ is going to require three components:
- A disease halting mechanism
- A neuroprotective agent
- Some form of cell replacement therapy
This week we got some interesting clinical news regarding the one of these components: A disease halting mechanism
Clinical trial results from Austria suggest that a new immunotherapy approach in people with Parkinson’s is both safe and well tolerated over long periods of time.
What is immunotherapy?
This week multiple research groups at the University of Oxford and Boston-based FORMA Therapeutics announced a collaboration to identify, validate and develop deubiquitinating enzyme (DUB) inhibitors for the treatment of neurodegenerative conditions, like Parkinson’s.
But what exactly are DUB inhibitors? And how do they work?
In today’s post, we will answer these questions, look at what the new collaboration involves, and look at what else is happening with DUB inhibitors for Parkinson’s.
Dubstep is a genre of electronic dance music that originated in South London in the late 1990s. Only recently -in the 2010s – has the culture really become more mainstream. And while I have a hard time appreciating the heavy bass music (man, I am becoming a grumpy old man before my time), it is amazing to watch some of the dancers who robotically embody this form of music:
The guy on the right is named Marquese Scott. Sometimes he simply defies the laws of physics.
The title of today’s post is a play on words, because rather than doing ‘Dubstep’ we are going to be discussing how to ‘DUB-stop’.
Researchers in Oxford have recently signed an agreement with a US company to focus resources and attention on a new approach for tackling neurodegenerative conditions, including Parkinson’s.
What they are proposing is a complicated biological dance.
Their idea: to stop deubiquitinating (DUB) enzymes.
What are deubiquitinating enzymes?
This is Mariëtte Robijn:
She’s really ‘leuk’ (Dutch for nice).
Diagnosed at 46 with Parkinson’s, Mariëtte keeps a great blog that touches on many areas of life, including boxing. But it also provides her with a medium to discuss how she lives with Parkinson’s (you should follow her if you don’t already).
In a recent post on her blog – called “Planet Patient vs Planet Researcher” – Mariëtte asks ‘are we really so very different, we patients and researchers?‘
Her answer is ‘Yes!‘ and she listed 10 areas where the differences are apparent.
Mariëtte’s points are made from an educated point of view – she is a very dedicated Parkinson’s research advocate.
Reading through her post, however, I saw it as a nice opportunity to provide the view of things from the other world (Planet Researcher). So, with her permission, I have copied her 10 points here and I have tried to provide a Planet Researcher view of her thoughts (below in red). And I should add that I do not speak for everyone on Planet Researcher – my views are simply that: mine.
In a recent SoPD post, we discussed the importance of calcium and looked at how it interacts with the Parkinson’s-associated protein alpha synuclein, affecting the function and clustering of that protein.
During the writing of that post, another interesting research report was published on the same topic of calcium and alpha synuclein. It involved a different aspect of biology in the cell – a structure called the endoplasmic reticulum – but the findings of that study could also explain some aspects of Parkinson’s.
In today’s post, we will review the new research report, consider the biology behind the findings and how it could relate to Parkinson’s, and discuss how this new information could be used.
The original berserker. Source: Wikipedia
I can remember my father often saying “If you kids don’t be quiet, I’ll go berserk!”
Growing up, I never questioned the meaning of the word ‘berserk‘.
I simply took it as defining the state of mindless madness that my dad could potentially enter if we – his off-spring – pushed him a wee bit too far (and for the record, Dad actually ‘going berserk’ was a very rare event).
My father. But only on the odd occasion. Source: Screenrant
But now as I find myself repeating these same words to my own off-spring, I am left wondering what on Earth it actually means?
What is ‘berserk‘?
At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during April 2018.
The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and a new feature: Review articles/videos).
So, what happened during April 2018?
In world news:
- April 4–15th – The 2018 Commonwealth Games were held in Gold Coast, Queensland, Australia (New Zealand came 5th in the medals tally… not bragging, just saying).
- April 27th – Kim Jong-un crosses into South Korea to meet with President Moon Jae-in, becoming the first North Korean leader to cross the Demilitarised Zone since its creation in 1953. In initial small steps towards reconciliation, South Korea said it would remove loudspeakers that blare propaganda across the border, while North Korea said it would shift its clocks to align with its southern neighbour.
BFFs? Source: QZ
- April 18th – NASA’s Transiting Exoplanet Survey Satellite (TESS) was launched. TESS will monitor more than 200,000 stars for temporary drops in brightness caused by planetary transits.
- And finally the city of Trier in Germany is already struggling to keep up with demand for ‘0-euro’ notes, bearing the face of its most famous son and communism’s creator Karl Marx. Sold for 3 euros each, the notes are part of celebrations for his 200th birthday (5th May 1818).
You get what you pay for. Source: DDR
In the world of Parkinson’s research, a great deal of new research and news was reported:
The cryptic title of this post will hopefully make sense by the time you have finished reading the material present here.
This week, new research from the USA points towards an increased risk of Parkinson’s (PD) for people that suffer from inflammatory bowel disease (IBD).
That same research, however, also points towards a clinically available treatment that appears to reduce the risk of Parkinson’s in individuals affected by inflammatory bowel disease. That treatment being: anti–tumor necrosis factor antibodies (TNF AB). Is that title making sense yet? If not, read on.
In today’s post, we will outline what inflammatory bowel disease is, review what the new research found, and discuss what is known about TNF in Parkinson’s.
Inflammatory bowel disease. Source: Symprove
Inflammatory bowel disease (or IBD) is one of these umbrella terms that is used to refer to a group of inflammatory conditions of the large and small intestine:
The large and small intestine. Source: Adam
The symptoms of IBD can include abdominal pain, diarrhoea, vomiting, rectal bleeding, severe internal cramps/muscle spasms in the region of the pelvis, and weight loss.
There has been an increased incidence of IBD since World War II, which could be associated with increased awareness and reporting of the condition, but it could also be linked with increases in meat consumption (Click here to read more about this). For example, in 2015, an estimated 1.3% of U.S. adults (3 million) were diagnosed with IBD, which was a large increase on the levels in 1999 (0.9% or 2 million adults – Source: CDC).
This is delightful, but what does it have to do with Parkinson’s?
So this week, an interesting study was published on the Journal of the American Medical Association – Neurology edition website:
Bumetanide (Bumex) is a diuretic drug (a medication that removes water, by increasing the production of urine). It is used to treat swelling caused by heart failure or liver or kidney disease.
Recently, researchers in France have been exploring its use in Parkinson’s, and their results are really interesting.
‘Interesting’ because they not only point towards a clinically available drug that could (potentially) be repurposed for the treatments of Parkinson’s, but they also help to explain how our brains control movement.
In today’s post we will review the new results, discuss what they suggest about our ability to move, and we will look at efforts to take this drug to the clinic for Parkinson’s.
Heart failure (sometimes referred to as congestive heart failure) occurs when the heart is unable to pump sufficiently enough to maintain the required blood flow to meet the body’s needs. The most common causes of heart failure include coronary artery disease, high blood pressure, atrial fibrillation,valvular heart disease, and lifestyle issues (such as excess alcohol use). Overall around 2% of adults have heart failure; in those over the age of 65, this percentage increases to 6–10%. In 2015, it was estimated to affected approximately 40 million people worldwide (Source).
Common symptoms include:
- shortness of breath
- excessive tiredness
- leg swelling.
A common treatment option for heart failure are diuretics.
What are diuretics?
Diuretics (sometimes called water pills) are medications that have been designed to increase the amount of water and salt expelled from the body as urine.
There are three types of diuretic medications. They are:
Thiazide diuretics are the most commonly prescribed, generally for the treatment of high blood pressure. This class of drugs not only decreases the level of fluids in your body, they also cause your blood vessels to relax. Potassium-sparing diuretics reduce fluid levels in your body without – as the label suggests – causing you to lose potassium. The other types of diuretics can cause you to lose potassium, which can result in other health complications such as arrhythmia.
And then there are loop diuretics, which also decrease the level of fluid in the body.
But some loop diuretics have additional properties. And today we are going to have a look at one of them in the context of Parkinson’s.
It is called Bumetanide.
Why is Bumetanide interesting for Parkinson’s?
A reader recently asked me about an experimental drug called Ibudilast.
It is a ‘Phosphodiesterase 4 inhibitor’.
Recently there was a very interesting result in a clinical trial looking at Ibudilast in a specific neurodegenerative condition. Sadly for the reader that condition was not Parkinson’s, in fact very little research has been done on Ibudilast in Parkinson’s
In today’s post we will look at what Phosphodiesterase inhibitors are, how they work, and discuss why Ibudilast may not be such a good experimental treatment for Parkinson’s.
On April 21-27th, 2018, the American Academy of Neurology (AAN) will hold their 70th Annual Meeting in Los Angeles (California).
I will not be at the meeting, but I will definitely be keeping an eye out for any news regarding the results of one particular clinical trial. At the meeting, a biopharmaceutical company called MediciNova Inc. will be presenting data regarding one of their clinical trials.
The presentation, entitled “Ibudilast – Phosphodiesterase Type 4 Inhibitor – Bi-Modal Therapy with Riluzole in Early Cohort and Advanced Amyotrophic Lateral Sclerosis (ALS) Patients – Final Report and Future Directions“ (Source) will be presented by principal investigator of the clinical study, Dr. Benjamin Rix Brooks, of the Carolinas HealthCare System’s Neuromuscular/ALS-MDA Center at Carolinas HealthCare System Neurosciences Institute.
Dr Brooks will be presenting the results of a single-center, randomized, double-blind, placebo-controlled clnical trial which was conducted to evaluate the safety, tolerability and clinical endpoint responsiveness of a drug called Ibudilast (or MN-166) in subjects with the neurodegenerative condition, Amyotrophic Lateral Sclerosis (or ALS – also known as motor neuron disease; Click here to read a previous SoPD post about ALS and Click here to learn more about this clinical trial).
What is Ibudilast?
Ibudilast is a phosphodiesterase inhibitor.
What is a phosphodiesterase inhibitor?
There has been a lot of discussion on this site (and elsewhere on the web) regarding the need for more objective systems of measuring Parkinson’s – particularly in the setting of clinical trials.
Yes, subjective reports of patient experience are important, but they can easily be biased by ‘placebo responses’.
Thus, measures that are beyond the clinical trial participants conscious control – and focused on biological outcomes – are needed.
In today’s post, we will consider one possible approach: Smart pills. We will discuss what they are, how they work, and how they could be applied to Parkinson’s research.
In order to encourage a growing discussion regarding objective measures of Parkinson’s (and to follow up on previous rants – Click here and here for examples), I have decided to regularly (once a month) highlight new technologies that could provide the sort of unbiased methods of data collection that are required for assessing whether a treatment is having an impact on Parkinson’s.
Today, we will look at smart pills.
What is a smart pill?