The road ahead: Parkinson’s research in 2019

 

“In preparing for battle I have always found that plans are useless, but planning is indispensable”

This quote has been attributed to General Dwight D. Eisenhower (Click here for the full story of this quote), and while the sentence does not immediately make a whole lot of sense, it does apply to our discussion here regarding research in Parkinson’s.

At the start of each year, it is a useful practise to layout what we are expecting and hoping to see in the world of Parkinson’s research over the next 12 months. This can help us better anticipate where ‘the battle’ may go, and allow us to prepare for things further ahead. Where it actually finishes is unpredictable, but where we currently stand will hopefully provide us with a useful measure.

In this post, I will lay out what we believe the next 12 months holds for us with regards to the Parkinson’s-related research.

And be warned: This is usually the longest post of the year.

 

Source: Protradeunited

In the introduction to last year’s outlook I wrote of the dangers of having expectations (Click here to read that post). A wise man (the great Charlie Munger) once said: If you want to lead a happy life, lower your expectations.

It is good advice, and as a rule, I try to follow it in life – I am a cup is completely empty kind of guy. I have no expectations, and so when anything happens – it is magic. I do have ambitions, but no expectations.

And others wrote about managing expectations in 2018 (Click here for a great example).

To put it plainly: Expectations are the primary cause of all disappointment.

Sage wisdom. Source: Unitystone

And it is important, as we look ahead at the next 12 months of Parkinson’s research, we need to be very careful not to have too many (or to build up too many) expectations.

 

Right, now, with all of that said, it may now befuddle some readers that the theme of the 2019 SoPD outlook is ‘great expectations‘.

Let me explain:

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2018: Year in review

 

In this end-of-year post we review the year that was 2018.

Month-by-month we will briefly discuss some of the major pieces of research/announcement that have define the year and advanced our understanding of Parkinson’s.

The list is based on nothing more than the author’s personal opinion – apologies to any researchers who feel left out.

And in the next post we will consider what the year ahead (2019) has in store for us.

 

Source: a-star

In the 525600 minutes that made up 2018, a lot happened in the world of Parkinson’s research.

A total of 7672 research papers were published with the keyword ‘Parkinson’s’ according to the Pubmed website (this compared to 7675 for all of 2017 – this obviously represents a dismal failure for the Parkinson’s research community: the first time in quite a while that we haven’t beaten the number of research reports from the previous year!

I am of course kidding. The quantity of research reports is irrelevant. But it does make me smile that we missed the mile stone by just 3 papers!

2018 has been another amazing year for Parkinson’s research. And while I appreciate that a comment like this means little to someone living with the condition on a day-to-day, remarkable progress has been made not only in our understanding of the condition, but also in the various ways in which the research is being done and potential therapies are approaching the condition.

In this post, we will review the year that was by briefly summarising some of the major research-related events of each month in 2018.

And that journey begins with:

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Monthly Research Review – December 2018

 

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 December2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 

 

So, what happened during December 2018?

In world news:

7th December  – The U.N.’s International Telecommunication Union reported that, by the end of 2018, more than half – a full 51.2 percent – of the world’s population will be using the Internet (Click here to read more about this).

 

8th December – Drama at the 24th Conference of the Parties to the United Nations Framework Convention on Climate Change (COP24) meeting in Katowice, Poland. The US, Saudi Arabia, Russia and Kuwait object to adopting the scientific report – which was commissioned at the 2015 meeting. The study suggests that the world is now “completely off track” on climate change, heading towards a 3 degree C. rise by the end of this century rather than a mere 1.5 degree C. rise (Click here to read more about this).

12th December – Negotiators at COP24 in Katowice finally secured an agreement on a range of measures that will make the Paris climate pact operational in 2020 (Click here to read more about this).

 

17th December – Astronomers announced that they have identified the most distant object ever observed within our solar system. Currently named “2018 VG18” (but nicknamed ‘Farout’), the 500km (310 miles) wide body is approximately is 120 times further away from the sun than Earth is (to put that in perspective, Pluto is only 34 times – Click here to read more about this).

 

In the world of Parkinson’s research, a great deal of new research and news was reported:

In December 2018, there were 597 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (7672 for all of 2018 – compared to 7675 for all of 2017….seriously?!? Just 3 papers difference?!?). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 5 pieces of Parkinson’s news

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From Alchemy to Alkahest

 

Numerous readers have asked about a curious new clinical trial being conducted by a biotech firm called ‘Alkahest’. The company has recently initiated a large (90 participants) Phase II study of their Parkinson’s-focused treatment called GRF6021.

This is an experimental, intravenously-administered treatment, which is derived from a components of blood.

In today’s post, we will discuss some of the research behind GRF6021, what this new clinical trial involves, and have a look at some other interesting Parkinson’s-related activities that Alkahest has ongoing.

 

Source: SFN

The Society of Neuroscience meeting is the largest annual research conference on brain relelated research, bringing approximately 40,000 neuroscientists together in October. At the Society of Neuroscience meeting in San Diego this year, however, there was considerable interest focused on several presentations dealing with blood.

The first presentation was from a group of researchers at the University of California, San Francisco.

The research team – led by group leader Dr Saul Villeda – were presenting new data suggesting that circulating immune cells were most likely responsible for the age-related reduction in neurogenesis (formation of new neurons) that occurs in certain areas of the brain (Click here to read the abstract for this presentation). They reported that the aged hematopoietic (blood) system led to impaired neurogenesis. Their take-home-message: the older the blood system, the less new cells being produced by the brain.

Sounds interesting right?

Well, at the same time in another part of the conference a second group of researchers were presenting equally impressive data: They have zeroed in of a small fraction of normal, young blood that they believe has interesting properties, particularly in reversing the cognitive deficits associated with aging mice (Click here to read the abstract of this presentation).

Their research has even narrowed down to a specific protein, called C-C chemokine receptor type 3 (or CCR3), which when inhibited was found to improve cognitive function and decreased neuroinflammation in aged mice (Click here to read the abstract of the presentation).

The humble lab mouse. Source: Pinterest

But specifically for our interests here at the SoPD, these same researchers displayed data which demonstrated that treatment with a novel fraction of human plasma resulted in significant improvements in motor function, cell survival and neuroinflammation three weeks after treatment in multiple mouse models of Parkinson’s (Click here to read the abstract of the poster).

(PLEASE NOTE: The author of this blog was not present at the SFN meeting and is working solely with the abstracts provided)

This second group of scientists were from a company called Alkahest, and they have recently started a clinical trial for people with Parkinson’s based on these results. That trial has garnered quite a bit of interest in the Parkinson’s community.What do Alkahest do?

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The Parkinson’s Nebula?

 

There is a great deal of interest in genetic risk factors in Parkinson’s at the moment. A number of companies are providing direct-to-consumer services which provide individuals with some information about their family history and whether they have any of the more common genetic variations that are associated with medical conditions, like Parkinson’s.

Recently a new genetic data company has started – called Nebula Genomics – and they are offering a slightly different kind of service.

While many of the direct-to-consumer genetic companies have a business model that involves selling on genetic information to third parties, Nebula is offering a more patient-empowering option.

In today’s post, we will discuss the genetics of Parkinson’s, what Nebula Genomics is offering, and how this new service could be useful for the Parkinson’s community.

 

Prof George Church. Source: Biospace

Professor George Church is a person most readers will have never heard of.

He is the Robert Winthrop Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT, and was a founding member of the Wyss Institute for Biologically Inspired Engineering at Harvard.

He has co-author of over 500 academic papers, 143 patents and co-founded 22 biotech companies. In addition, he has participated in technology development, advising most of the major Genetic Sequencing companies, and he has been at the forefront of genetic research since the 1980s when he was involved with setting up the Human Genome Project.

His impact in the world of genetics has been tremendous.

But Prof Church is also something of a maverick. A left-field thinker. A disrupter.

He is a great supporter of open access genome sequencing and shareable human medical data. He is also keen to bring back extinct species, such as the Woolly Mammoth (Click here for more on this idea).

The return of the woolly mammoth. Source: Phys

Most recently, however, his name has been associated with a new company called Nebula Genomics.

What does Nebula Genomics do?

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EuPaTh: The Italian connection

 

The SoPD has a policy of not advertising or endorsing products/services.

This rule is in place to avoid any ethical/conflict of interest situations. It does little, however, to stop folks from bombarding the comments sections with links for wondrous magical cures which probably involve more ‘magical’ than actual cure.

Having said all that, every now and then I find or read about something that I think may be of interest to readers. In many of those cases, I can not vouch for the information being provided, but where I think there is the potential for readers to benefit, I am happy to take a chance and share it.

Today’s post is all about one such case: The European Parkinson Therapy Centre

 

Until very recently, I was working in Parkinson’s research centre in Cambridge (UK).

I conducted both lab- and clinic-based research on Parkinson’s in the lab of Prof Roger Barker. And it was in the clinic – several years ago – that I started hearing about a mysterious place that was not offering ‘to cure’ people of Parkinson’s, but rather helping them to live a better life with the condition.

Initially it was just a trickle of questions:

“Have you ever heard of this therapy place in Europe for people with Parkinson’s?” (“Nope, sorry” was my response).

But then an individual came in for their assessment, and spoke with tremendous enthusiasm about their own personal experience of visiting “this wonderful place in Italy” (“Sounds very interesting,” was my response, “Tell me more“).

Gradually, more and more people started sharing their own stories with me (both in the clinic, at support group meetings, and via correspondence to the SoPD website) about the place in Italy. And eventually it all led to me making some inquiries about the European Parkinson Therapy Centre.

What is the European Parkinson Therapy Centre?

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The lipidomics of Parkinson’s

 

Lipids are ‘waxy’ molecules that make up a large proportion of your brain and they play very important roles in normal brain function. For a long time researchers have also been building evidence that lipids may be involved with neurodegenerative conditions as well.

Recently, new research was presented that supports this idea (in the case of Parkinson’s at least), as two research groups published data indicating that certain lipids can influence the toxicity of the Parkinson’s associated protein alpha synuclein.

One of those research groups was a biotech company called Yumanity, and they are developing drugs that target the enzymes involved with the production of the offending lipids.

In today’s post, we will look at what lipids are, what the new research suggests, and discuss some of the issues that will need to be considered in the clinical development of these lipid enzyme inhibitors.

 

Yummy. Source: Healthline

Adherence to the ‘Mediterranean diet‘ has been associated with a reduced risk of developing Parkinson’s (Click here and here to read more about this), but no one has ever really explained why.

There has been the suggestion from some corners that this association may be due to the richness of monounsaturated fats in the foods generally included in this diet.

For example, olive oil is rich in monounsaturated fat.

What are monounsaturated fats?

Mmmm, before I answer that we need to have a broader discussion about “what is fat?“.

Fat is one of the three main macronutrients (carbohydrate and protein being the other two) that the body requires for survival.

Source: Visionpt

Fat serves as a ready source of energy for the body and can also provide insulation against cold temperatures or compression. All fats are derived from combinations of fatty acids (and also glycerol).

What are fatty acids?

A fatty acid is simply a chain of hydrocarbons terminating in a carboxyl group (having a carbonyl and hydroxyl group both linked to a carbon atom). Don’t worry too much about what that means, just understand that fatty acids are basically chains of hydrocarbons that look like this:

A chain of hydrocarbons ending in a carboxyl group (right). Source: Wikipedia

Fatty acids come in two forms:

  • Saturated
  • Unstaturated

In the case of a saturated fat, each carbon molecule in the chain of hydrocarbons is bonded to two other carbons by a single bond. Whereas in the case of a saturated fat, one or more carbon molecule in the chain of hydrocarbons is bonded to another carbon molecule by a double bond. For example:

Saturated fatty acids vs unsaturated fatty acids. Source: Medium

And unsaturated fatty acids can be further divided into:

  1. Monounsaturated fatty acids (or MUFAs) are simply fatty acids that have a single double bond in the fatty acid chain with all of the remainder carbon atoms being single-bonded.
  2. Polyunsaturated fatty acids (or PUFAs) are fatty acids that have more than one double bond.

Source: Medium

OK, but how might monounsaturated fats be involved with Parkinson’s?

That, dear reader, is the focus of numerous studies in the field of lipidomics.

What is lipidomics?

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Denali: Phase Ib clinical trial starts

 

Biotech firm Denali announced the dosing of the first person in their Phase Ib clinical study of their experimental treatment for Parkinson’s called DNL201.

DNL201 is an inhibitor of a Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (LRRK2).

In Parkinson’s, there is evidence that LRRK2 is over activate, and by inhibiting LRRK2 Denali is hoping to slow the progression of Parkinson’s.

In today’s post, we will discuss what LRRK2 is, what evidence exists for DNL201, and what the new clinical trial will involve.

 

 

Founded in 2013, by a group of former Genentech executives, San Francisco-based Denali Therapeutics is a biotech company which is focused on developing novel therapies for people suffering from neurodegenerative diseases. Although they have product development programs for other condition (such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease), Parkinson’s is their primary interest.

And their target for therapeutic effect?

The Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (or LRRK2).

What is LRRK2?

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The good, the GAD, and the not-so ugly

 

This post is a game of two halves.

The first half will explain the concept of a surgical procedure for Parkinson’s called ‘subthalamic deep brain stimulation‘, in which doctors permenantly implant electrodes into the brain to stimulate a region – the subthalamic nucleus. By stimulating this region with electrical impulses, doctors can provide a better quality of life (in most cases) to people with severe features of Parkinson’s.

In the second half of this post, we will look at an approach to doing the same thing,… but without the electrodes.

Rather, researchers are using gene therapy.

In today’s post, we will discuss what deep brain stimulation is, what gene therapy is, and how the gene therapy approach is having a different kind of impact on the brain to that of deep brain stimulation.

 

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Source: Youtube

Welcome to the first half of today’s post.

It begins with you asking the question:

What is deep brain stimulation?

Deep brain stimulation (or DBS) is a treatment method that involves embedding electrodes into the brain to help modulate the brain activity involved in movement.

It is a prodcedure that is usually offered to people with Parkinson’s who have excessive tremor or debilitating dyskinesias.

First introduced in 1987, deep brain stimulation consists of three components: the pulse generator, an extension wire, and the leads (which the electrodes are attached to). All of these components are implanted inside the body. The system is turned on, programmed and turned off remotely.

Shahlaie_DBS_Illustration-full

Source: Ucdmc

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Not bohemian, just ‘Rapsodi’

 

Moving forward into 2019 and beyond, we are going to be getting more sophisticated and targetted with our clinical trials for Parkinson’s. We are gradually moving away from the days when a drug was tested on anyone in the Parkinson’s-affected community, and heading for an age of sub-type specific treatments (Click here for a previous SoPD post on subtyping efforts for PD).

As part of this shift, there are a series of ongoing studies that are trying to identify not only the clinical & biological characteristics of those Parkinson’s sub-types, but also individuals who may already be in those groupings.

One such study is called “Rapsodi” – and it is focused on the identification of people with a particular genetic risk factor of PD – the GBA gene – who also demonstrate the early signs of Parkinson’s.

In today’s post, we will discuss what GBA is, how it is associated with Parkinson’s, and why the Rapsodi study is worthy of the PD community’s attention.

 

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Ambroxol. Source: Skinflint

The clinical trial of Ambroxol in Parkinson’s that has been conducted in London (UK) is close to announcing their final results. The Ambroxol study report should be published in early 2019.

What is the ambroxol study?

Started in February 2017, the Ambroxol study (named AiM-PD – Ambroxol in Disease Modification in Parkinson Disease) is a phase IIA prospective, single-centre, open label clinical trial to evaluate the safety, tolerability and pharmacodynamic effects of Ambroxol in Parkinson’s (Click here to read more about this trial and click here for the press release announcing the start of the study).

This trial, which is funded by the Cure Parkinson’s Trust and the Van Andel Research Institute (USA), has been conducted at the Royal Free Hospital in London (UK). The study has involved 20 people with Parkinson’s self-administering Ambroxol (in 60 mg per tablet) over a 6 month time frame. The participants were given 5 escalating doses of the drug for the first few weeks of the study (from 60 mg three times per day, gradually building up to 420 mg three times a day after the first month of the study).

But hang on a second. What is exactly is Ambroxol?

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