A.S.A.P

 

 

Yesterday the Aligning Science Across Parkinson’s (ASAP) initiative published a point of view in the scientific journal eLife. It laid out the objectives, themes and philosophy of an enormous new scientific effort to better understand Parkinson’s. The overall project is being led by a Nobel prize winner scientist and employing the considerable resources of a very wealthy family that has been affected by Parkinson’s. In today’s post we will have a look at what the ASAP initiative is planning to do and how it will hopefully significantly enhance our understanding of Parkinson’s.

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Google co-founder Sergey Brin. Source: Emaze

Every so often something comes along that is so ‘next level’ in its scale and ambition that it gives you pause.

Two years ago, key Parkinson’s researchers from around the world were invited to the Milken Institute Center in for a grand meeting that was organised to plan out the foundations of a major new Parkinson’s research program that was to be called Aligning Science Across Parkinson’s (or ASAP).

The event was organised by Google co-founder Sergey Brin and his family foundation. The Brin family have been affected by Parkinson’s (Sergey’s mother and aunt both have the condition, and Sergey has a genetic risk factor that increases his risk of developing Parkinson’s).

The Brin Family – Sergey and his mother on the right. Source: CS

Sergey and his mother both carry a genetic variation in a region of DNA called PARK8. It is also known as Leucine-rich repeat kinase 2 (or simply LRRK2 – pronounced ‘lark 2’). The variant increases the risk of developing an young-onset, slow progressing form of Parkinson’s (Click here to read more about LRRK2). Sergey may never develop the condition, but he has decided not to take any chances. He has taken out an “insurance policy” by investing hundreds of millions of dollars into Parkinson’s research.

Part of that insurance policy is the ASAP effort.

And ASAP is being coordinated by Prof Randy Schekman.

Who is Prof Randy Schekman?

Prof Schekman is an investigator of the Howard Hughes Medical Institute (only the best of the best get selected for the HHMI) and a Professor of Cell and Developmental Biology with a research group in the Department of Molecular and Cell Biology at the University of California at Berkeley.

Prof Randy Schekman. Source: Jiqizhixin

He was also co-awarded the Nobel prize in physiology or Medicine in 2013 along with James Rothman and Thomas Sudhof “for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells”.

Schekman donated his share of the Nobel prize money ($400,000) to UC Berkeley for the creation of an endowment for the Esther and Wendy Schekman (his mother and sister who both died of cancer) Chair in Basic Cancer Biology.

He has won more prizes and honors than I have had hot meals. It is without any doubt that we can say he is an eminent scientist.

Why has he turned his attention to Parkinson’s?

For Prof Schekman, the ASAP initiative is not simply a scientific interest, but a personal mission:

His late wife had Parkinson’s.

What does ASAP want to do?

ASAP “will allocate financial resources that significantly enlarge the basic science effort currently supported by the government and private foundations with the goal of understanding the underlying biology of Parkinson’s“.

And how do they plan to do this?

After a series of meeting over the last two years, the ASAP project has come up with a series of objectives and themes that they have laid out in a point of view piece that was published yesterday in the prestigious OPEN ACCESS research journal “eLife“.

Here is the point of view:

Title: Coordinating a new approach to basic research into Parkinson’s disease
Authors: Schekman R, Riley EAU
Journal: eLife 2019;8:e51167
PMID: N/A                (This report is OPEN ACCESS if you would like to read it)

As the two authors state in their intro, one of the problems with Parkinson’s research at present is that funding for the research is low.

“In the United States, for example, the economic burden of PD is estimated to be $52bn per year, yet the National Institutes of Health (NIH) only spent an estimated $168 m on PD research in FY 2017 (which was just 6.5% of what it spent on neurodegenerative diseases). And although two non-profit organizations – the Michael J. Fox Foundation for Parkinson’s Research and the Parkinson’s Foundation – spent a further $108 m on PD research in FY 2017, it is estimated that 1.04 million Americans have PD, so total spending on research is about $265 per patient”

One obvious solution to this situation is to inject a serious amount of additional funding (and this is where Sergey comes into the picture).

This new funding will be introduced via a research roadmap that focuses on three scientific themes:

The eLife article expands on each of these themes:

Biology of PD-associated genes – ASAP notes that DNA analysis “studies have identified nearly 90 risk loci for Parkinson’s, perhaps 20 of which are considered causal” (Click here for a good read on this topic). We know quite a bit about some of these genetic risk factors (think: alpha synuclein, LRRK2, GBA,…), but next to nothing about most of the others with regards to their actual function. We need to know more about these other genetic risk factors.

For those readers who are unfamilar with the current ideas regarding the genetics of Parkinson’s (and how a better knowledge of it could be used to design therapies for the condition), this video might be useful:

Neuro-immune interactions – As authors wrote in the point of view: “Recent research suggests that Parkinson’s is not purely a neurodegenerative disease of the brain, but involves peripheral organ systems including the immune system and microbiome“. We are really only just beginning to explore the complexity of organs like the gastrointestinal system and its potential influence on the course of Parkinson’s. How these other organs in the body are interacting with the immune system and brain may be fundamental to our ability to actually properly treating the condition.

Circuitry and brain-body interactions – given that we are increasingly viewing Parkinson’s as a multisystem disorder (not just the brain, but also the gut, etc), ASAP believes we require a more holistic approach. And within the brain, we need to look beyond the dopamine neurons, and ASAP is excited about exploring “how new tools developed through the BRAIN Initiative could be integrated into basic Parkinson’s research“.

A fourth theme will be progression which is “interconnected with each of the aforementioned themes, as progression affects every aspect of the underlying disease pathology“.

The overall goal of ASAP is “to fund a basic research program that amplifies and coordinates the efforts of researchers around the world, both inside and outside of the existing Parkinson’s community“.

In addition to these themes and grand goal, however, ASAP also has some major objectives which could be rather transformational for the way we conduct research. These objectives include:

• Supporting meaningful collaboration (the point of view discusses this particular topic at length)
• Generating research resources
• Democratizing data

And these objectives will apply to all of the themes mentioned above:

The point of view piece lays out certain requirements for researchers being awarded funding from ASAP, such as making tools, resources, and data openly available. Manuscripts of completed studies will be made available on preprint websites like bioRxiv and publishing the results only in journals “that offers immediate open access with a Creative Commons CC-BY license, in clear alignment with Plan S principles“.

And ASAP “will also seek to open lines of communication to the public, especially to patient groups“. The important part of it all will be the need for collaboration.

In generating new tools/resources there will apparently be a strong focus on the enabling of biomarker discovery (a much needed component of better assessing and tracking Parkinson’s).

And ASAP will also put effort into making “data and other research objects discoverable, publicly available, and fully integrated into the PD data ecosystem”. It all sounds very good.

What are we hoping for from ASAP?

Beyond a better understanding of basic biology of Parkinson’s and oh, maybe a cure?

Let’s get specific (and maybe irritate a few people). Here at the SoPD, we are hoping to see:

1. No research focused on alpha synuclein (it is by far the most studied Parkinson’s-associated protein, there are multiple clinical trials targeting it, and we really need to focus resources elsewhere).
2. A re-defining of what we mean when we say “Parkinson’s disease” (Parkinson’s advocate Ben Stecher recently discussed this issue – click here to read more about this).
3. Major collaboration with other significant Parkinson’s research efforts (such as the NIH Accelerating Medicines Partnership – Parkinson’s, which should be rolling out soon as well) and non-Parkinson’s research efforts (such as Accelerating Medicines Partnership – Alzheimer’s and Accelerating Medicines Partnership – heumatoid arthritis and lupus).
4. The ASAP programme have impact on other forms of Parkinsonisms (such as Progressive supranuclear palsy (PSP) or Multiple System Atrophy (MSA)) as well as other medical conditions beyond just Parkinson’s.
5. The patient voice – by this I mean that the current view point/themes/objectives read like they have been written by scientists. And I get it that the “Aligning Science Across Parkinson’s” project is focused on the “basic biology” of Parkinson’s. But my reading is that there is an absence of patient involvement in planning of this (and I would be very happy to be corrected on this). And if it is not patient-focused, then what is it?

So what does it all mean?

The Sergey Brain family foundation – which is already a major contributor to Parkinson’s research via donations to major charities – is about to start a MAJOR new project that will have the goal of enhancing our understanding about the basic biology of this neurodegenerative condition and help to identify novel potential therapies.

To say that I am HUGELY excited by the ASAP project would be a gross understatement. I have been looking forward to ASAP kicking off since I first heard about it in 2017. It is an EXTREMELY positive step forward for the Parkinson’s community. And you will be reading a lot more about it here on the SoPD as progress is made on the project.

Starting on the 15th October (2019), there will be an international call for pre-proposals for research funding and a little bird has told me that it is going to be massive! We already know from the point of view piece that ASAP will be awarding up to $9 million per research team over a three year period (understand that that is a transformational amount of money for the vast majority of research labs, and it would allow some scientists to test some extremely ambitious ideas – click here to read more about the funding).

Very exciting stuff for the Parkinson’s research community.

 

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The banner for today’s post was sourced from ASAP