One of the most common questions I get from SoPD readers is what’s new with inflammasome research? Another version of this question is where are the clinical trials for NLRP3 inhibitors in Parkinson’s?
Readers have become very enchanted by this new class of anti-inflammatory drugs as a potential future treatment for Parkinson’s – and there is preclinical evidence to support this vibe. But the clinical development of these experimental therapies has been slow.
Recently, the pharmaceutical company Roche has initiated Phase 1b testing of their NLRP3 inhibitor (called Selnoflast) in people with Parkinson’s – the first in this class.
In today’s post, we will discuss what the inflammasome is, how NLRP3 inhibitors work, and what the new clinical trial involves.
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On the 21st September 2020, the website for an Ireland-based biotech company called Inflazome suddenly disappeared. In its place was a single page, that stated the large pharmaceutical company Rochehad purchased the biotech firm and taken on all of its inflammasome-targeting intellectual property (Source).
This was a big deal for folks who were watching the inflammasome research world. It suggested that the big players (pharma) were now interested in this space ($449 million interested in the case of Inflazome). And since then, there has been a rush of other pharma companies buying or developing inflammasome-targeting agents.
The Inflazome purchase was also interesting because the company was targeting Parkinson’s as one of their indications of interest.
And it would appear that Roche is now following up on this interest, having initiated a clinical trial program focused on inflammasomes in Parkinson’s.
Hang on a second. Remind me, what are inflammasomes?
Over the past two decades, pharmaceutical companies have shifted from maintaining large in-house drug development platforms to a model that involves acquiring small biotech firms with interesting agents once those companies reach a certain point in their maturation.
This week a biotech firm called Inflazome was bought by the big pharma Roche.
Inflazome has been developing a novel NLRP3 inhibitor, which targets inflammasome activation and the company has had Parkinson’s in it’s sights as far as indications of interest.
In today’s post, we will discuss what the inflammasome is, how NLRP3 inhibitors work, and what will be happening next.
One of the hottest areas of Parkinson’s research world is ‘inflammation‘ (cheesy pun intended).
What is inflammation?
When cells in your body are stressed or sick, they begin to release tiny messenger proteins which inform the rest of your body that something is wrong.
When enough of these messenger proteins are released that the immune system becomes activated, it can cause inflammation.
Inflammation is a critical part of the immune system’s response to trouble. It is the body’s way of communicating to the immune system that something is wrong and activating it so that it can help deal with the situation.
By releasing the messenger proteins (called cytokines), injured/sick cells kick off a process that results in multiple types of immune cells entering the troubled area of the body and undertaking very specific tasks.
Inflammation is part of the immune system’s response to damage or infection. It is a very natural process that our bodies undergo when we come into harms way.
Researchers at the University of Queensland, have recently demonstrated something interesting about the inflammation associated with Parkinson’s: by inhibiting a very specific part of the inflammatory process, they can reduce the spread of Parkinson’s associated alpha synuclein pathology in models of PD.
And they have developed a drug – called MCC950 – that specifically targets that component of the inflammation process which they are now seeking to test in clinical trials.
In today’s post, we will discuss what inflammation is, review this new research, and consider what it could all mean for the Parkinson’s community.
Spot the unhealthy cell – exhibiting signs of stress (yellow). Source: Gettyimages
No silly preamble today – this is going to be a very long post, so we’re diving straight in:
When cells in your body are stressed or sick, they begin to release messenger proteins which inform the rest of your body that something is wrong.
When enough cells release these messenger proteins, it can cause inflammation.
What is inflammation?
Inflammation is a vital part of the immune system’s response to trouble. It is the body’s way of communicating to the immune system that something is wrong and activating it so that it can help deal with the situation.
By releasing the messenger proteins, injured/sick cells kick off a process that results in multiple types of immune cells entering the troubled area of the body and undertaking very specific tasks.
In December of of 2017, the results of a clinical trial suggested that a particular kind of exercise may have beneficial effects against certain aspects of Parkinson’s. Specifically, a high-intensity treadmill regime was found to be ‘non-futile’ as an intervention for the motor symptoms in de novo (newly diagnosed) Parkinson’s.
Recently, however, new pre-clinical research has been published which reported that when mice with particular Parkinson’s-associated genetic mutations are exercised to exhaustion, they have high levels of inflammation which can exaggerate the neurodegeneration associated with that model of PD.
So naturally, some readers are now asking “So should I be exercising or not?!?”
In today’s post we will review the results of the two studies mentioned above, and discuss why exercise is still important for people with Parkinson’s.
Readers are recommended to click on the image above and listen to the music (Michael Sembello’s “Maniac” from 1983) whilst reading this post.
This song was made famous by one particular scene from the 1983 movie “Flashdance” starring Jennifer Beals, in which the lead character undertook an intense dance routine. Ever since that iconic scene, exercise fanatics have long used the music to help get themselves into the mood for their workouts.