Genetic variations in a region of our DNA called PARKIN is associated with an increased risk of developing Parkinson’s – particularly young-onset PD (diagnosed before the age of 40yrs).
This area of DNA provides the instructions for making a protein (also referred to as PARKIN), which plays a number of important roles inside of cells.
Recently, a South Korean biotech company called Cellivery has published research on an experimental therapeutic agent that easily penetrates both the brain and cells within, delivering PARKIN protein to the cells that need it.
In today’s post, we will discuss what PARKIN does, review the new research report, and explore what could happen next.
Here on the SoPD we often talk about research regarding the prominent Parkinson’s associated proteins, think of alpha synuclein, LRRK2 and GBA. And they are of interest as there is a great deal of activity now at the clinical level exploring agents targetting these proteins.
But there are a number of interesting therapeutics being developed that are exploring some of the other Parkinson’s-associated proteins.
A good example was published this week:
Title: Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein
Authors: Chung E, Choi Y, Park J, Nah W, Park J, Jung Y, Lee J, Lee H, Park S, Hwang S, Kim S, Lee J, Min D, Jo J, Kang S, Jung M, Lee PH, Ruley HE & Jo D
Journal: Science Advances, 29 Apr 2020:6, 18, eaba1193
In this study, South Korean researchers demonstrated that a brain penetrating compound (including the PARKIN protein) can rescue numerous models of Parkinson’s.
Hang on a second: What is PARKIN?
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This week the outcome of an ongoing Parkinson’s clinical trial was announced.
Data collected during Part 1 of the ongoing Phase 2 PASADENA alpha synuclein immunotherapy study for Parkinson’s apparently suggests that the treatment – called prasinezumab – has not achieved it’s primary endpoint (the pre-determined measure of whether the agent has an effect in slowing Parkinson’s progression – in this case the UPDRS clinical rating scale).
But, intriguingly, the announcement did suggest ‘signals of efficacy‘ in secondary and exploratory measures.
In today’s post, we will discuss what immunotherapy is, what we know about the PASADENA study, and why no one should be over reacting to this announcement.
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At 7am on Wednesday, April 22nd, 2020, the pharmaceutical company Roche published its sales results for the 1st Quarter. This was just prior to the opening of the Swiss Stock Exchange. The financial report looked very good, particularly considering the current COVID-19 economic climate.
There was, however, one sentence on page 133 of the results that grabbed some attention:
For those of you (like myself) who struggle with fine print, the sentence reads:
“Study did not meet its primary objective, but showed signals of efficacy“
This was how the pharmaceutical giant announced the top line result of the ongoing Phase II PASADENA study evaluating the immunotherapy treatment prasinezumab in recently diagnosed individuals with Parkinson’s (listed on the Clinicaltrials.gov as NCT03100149).
At the time of publishing this SoPD post, Roche are yet to provide any further information (press release, announcement, memo, tweet, etc) regarding the results of the study.
Thankfully, a smaller biotech firm called Prothena – which is also involved in the development of the agent being tested in the Pasadena study – has kindly provided a few more details regarding these results.
In today’s post we will discuss what details have been shared in the Prothena press release regarding the Prasinezumab clinical trial in Parkinson’s (Click here to read the press release).
What is Prasinezumab?
Last week the German biotech firm MODAG announced that they had secure €12M in series A funding from various venture capital investors.
The company is going to use those funds to clinically develop their lead compound – Anle138b – in the neurodegenerative condition, Multiple Systems Atrophy (or MSA).
In today’s post, we will discuss how Anle138b works, what Multiple Systems Atrophy is, and how this news could be good for the Parkinson’s community.
Stealth mode. Source: Hackernoon
Last week a small biotech firm in Germany came out of ‘stealth mode’.
What is stealth mode?
According to wikipedia, “in business, stealth mode is a company’s temporary state of secretiveness, usually undertaken to avoid alerting competitors to a pending product launch or other business initiative”.
After years of developing a novel drug, the German company emerged from stealth mode with €12M in series A funding, which will be used to clinically test their new treatment.
The company’s name is MODAG.
They are planning to clinically test their lead compound which is called Anle138b.
The initial Phase I safety test will be conducted in healthy individuals, but then they will turn their attention to individuals with multiple systems atrophy.
What is Multiple System Atrophy?
Alpha synuclein is a protein that is closely associated with Parkinson’s. But exactly if and how it is connected to the neurodegenerative process underlying the condition, remains unclear.
Last week researchers reported that removing a particular form of alpha synuclein in mice results in a very early onset appearance of characteristics that closely resemble the features of Parkinson’s that we observe in humans. This finding has caused some excitement in the research community, as not only does this tell us more about the alpha synuclein protein, but it may also provide us with a useful, more disease-relevant mouse model for testing therapies.
In today’s post, we will discuss what alpha synuclein is, explain which form of the protein was disrupted in this mouse model, review the results of the new study, and look at how tetramer stablising drugs could be a new area of PD therapeutics.
The 337 metre (1,106 ft) long USS Gerald R. Ford. Source: Wikipedia
Imagine you and I are standing in front of the world’s largest aircraft carrier, the USS Gerald R. Ford.
It is a VAST warship – measuring in at 337 metres (1,106 ft) in length, 76 metres (250 feet) in height – and it is a wonder of engineering composed of over a billion individual components.
And as we are standing there, gazing up at this amazing machine, I turn to you and put a nut & bolt into the palm of your hand.
A nut and bolt. Source: Atechleader
You look down at it for a moment, then turn to me, puzzled.
And that is when I say: “I would like you to find (without aid/instructions) where on this ship versions of this particular type of nut and bolt live, and try to determine exactly what functions they have“.
Where would you even start?
What tools would you use for the job? Considering the size and complexity of the vessel, would you simply give up before even starting?
It sounds like a ridiculously daunting task, but this is in effect what neurobiologists are trying to do with their study of the brain. They start with a protein – one of the functional pieces of machinery inside each cell of our body – and then try to determine where in the brain it lives (the easy part) and what it does exactly (the REALLY hard part – most proteins have multiple functions and different configurations).
A good example of this is the Parkinson’s-associated protein alpha synuclein:
Alpha synuclein. Source: Wikipedia
Alpha synuclein is one of the most abundant proteins in our brains – making up about 1% of all the proteins floating around in each neuron in your head – and it is a very well studied protein (with over 9700 research reports listed on the Pubmed search engine with the key words ‘alpha synuclein’).
But here’s the thing: we are not entirely clear on what alpha synuclein actually does inside the cell.
In fact, biologists are not even sure about what the ‘native’ form of alpha synuclein is!
What do you mean?
This week, biotech firm Prothena published the results of their Phase I safety and tolerance clinical trial of their immunotherapy treatment called PRX002 (also known as RG7935).
Immunotherapy is a method of artificially boosting the body’s immune system to better fight a particular disease.
PRX002 is a treatment that targets a toxic form of a protein called alpha synuclein – which is believed by many to be one of the main villains in Parkinson’s.
In today’s post, we will discuss what immunotherapy is, review the results of the clinical trial, and consider what immunotherapy 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.
The Phase I results of a clinical trial being conducted by a company called Prothena suggest that a new immunotherapy approach in people with Parkinson’s is both safe and well tolerated over long periods of time.
The good folks at Prothena Therapeutics. Source: Prothena
What is immunotherapy?