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Today’s post is ‘blue sky’ stuff (meaning that it is not going to be in the clinical any time soon), but it is utterly fascinating (almost sci fi) research.
Scientists at Stanford University have developed a method by which they can reprogram cells to use synthetic materials (provided by the scientists themselves) to build functional artificial structures.
And to add to the sci fi nature of it, they have called this approach “GTCA” (“genetically targeted chemical assembly”).
In today’s post, we discuss what GTCA is, what they found in their study, and where this wondrous discovery could go next.
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Prof Karl Deisseroth. Source: Ozy
This is Karl Deisseroth.
Looks like the mad scientist type, right? Well, remember his name because this guy is fast heading for a Nobel prize.
He is the D. H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University. And he is one of the leading researchers in a field that he basically started. That field is called optogenetics (Click here to read a previous SoPD post about this topic).
Optogenetics. Source: Harvard
He also developed (along with Kwanghun Chung) a better way of visualising the brain called CLARITY.
CLARITY is a technique that transforms intact tissue (like the brain) to make it completely transparent. With a clear brain – and some additional biological techniques – an exceptionally detailed map of neuronal pathways can be generated.
For an example, watch this video:
Prof Deisseroth and colleagues are also seeking to pioneer additional areas of neuroscience, and in today’s post we will be exploring a new research report that could have important implications for Parkinson’s.
Here on the SoPD we often discuss research focused on the slowing or stopping of Parkinson’s, but often overlooked are efforts to restore and rejuvenate. Replace the lost cells and circuits that have been lost to degeneration.
At the start of this year (in the 2020 wish list post), I said that I was hoping to see “a focus on rejuvenation”.
And it is fair to say that Prof Deisseroth and colleagues appear to be trying to deliver on that particular wish.
Interesting. What have Prof Deisseroth and his team done?
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?
Nuclear receptor related 1 protein (or NURR1) is a protein that has been shown to have a powerful effect on the survival of dopamine neurons – a population of cells in the brain that is severely affected by Parkinson’s.
For a long time researchers have been searching for compounds that would activate NURR1, but the vast majority of those efforts have been unsuccessful, leaving some scientists suggesting that NURR1 is “undruggable” (meaning there is no drug that can activate it).
Recently, however, a research report was published which suggests this “undruggable” protein is druggable, and the activator is derived from a curious source: dopamine
In today’s post, we will discuss what NURR1 is, what the new research suggests, and how this new research could be useful in the development of novel therapeutics for Parkinson’s.
It always seems impossible until it’s done – Nelson Mandela
In 1997, when Nelson Mandela was stepping down as President of the African National Congress, some researchers in Stockholm (Sweden) published the results of a study that would have a major impact on our understanding of how to keep dopamine neurons alive.
(Yeah, I know. That is a strange segway, but some of my recent intros have dragged on a bit – so let’s just get down to business)
Dopamine neurons are of the one groups of cells in the brain that are severely affected by Parkinson’s. By the time a person begins to exhibit the movement symptoms of the condition, they will have lost 40-60% of the dopamine neurons in a region called the substantia nigra. In the image below, there are two sections of brain – cut on a horizontal plane through the midbrain at the level of the substantia nigra – one displaying a normal compliment of dopamine neurons (on the left) and the other from a person who passed away with Parkinson’s demonstrating a reduction in this cell population (on the right).
The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinsonian brain (right). Source:Memorangapp
The researchers in Sweden had made an amazing discovery – they had identified a single gene (a specific region of DNA) that was critical to the survival of dopamine neurons. When they artificially disrupted the section of DNA where this gene lives – an action which resulted in no protein for this gene being produced – it resulted in mice being born with no midbrain dopamine neurons:
Title: Dopamine neuron agenesis in Nurr1-deficient mice
Authors: Zetterström RH, Solomin L, Jansson L, Hoffer BJ, Olson L, Perlmann T.
Journal: Science. 1997 Apr 11;276(5310):248-50.
The researchers who conducted this study found that the mice with no NURR1 protein exhibited very little movement and did not survive long after birth. And this result was very quickly replicated by other independent research groups (Click here and here to see examples)
So what was this amazing gene called?
Nuclear receptor related 1 protein (or NURR1; it is also known as NR4A2 – nuclear receptor subfamily 4, group A, member 2)
And what is NURR1?
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?