Monitoring an Apple in motion

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Wearable technology offers the potential to more accurately monitor the symptoms of Parkinson’s in real time. Such information could allow for better and more precise management of the condition, as well as providing objective measures for clinical trials exploring novel therapies.

Assessing some of the features of Parkinson’s, however, is not easy. Differentiating jerky involuntary movements like tremor or dyskinesias from planned movements like typing or shaking someone’s hand has proven difficult

Recently, researchers at the tech giant Apple have been applying some focus to this problem and they are now sharing their results with the Parkinson’s community.

In today’s post, we will review a research report presenting the results of the Apple study and discuss other recent events in wearable tech for Parkinson’s.

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Source: Tes

I used to be an Apple fan back in the day (mid-late 2000s). Wonderful user interface, superb design, lovely innovative products.

But I have to admit: gradually over time I became disenchanted with them.

Why?

The products became too expensive, the “Walled garden” mentality around the operating system frustrated me, and there has been a lack of serious innovation (a new iteration on a phone or tablet every year just doesn’t cut it… and now they are thinking of getting into the crowded space of electric cars… yippee, inspiring stuff).

Maybe we came to expect too much from them, but (personal opinion here) I think they lost their fanatical drive in the absence of Steve.

Source: Dansilvestre

[Positive way to start a post on, huh? It gets better. Stay with me]

All of that said, Apple published a research report earlier this year that deserves the Parkinson’s community’s attention and respect.

What did they report?

Continue reading “Monitoring an Apple in motion”

G.P.N.M.B

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There is a critical need for good biomarkers in neurodegenerative research.

A biomarker is an objective indicator of a medical state that can be assessed from outside a patient, and can be measured accurately and reproducibly. It could come in the form of a medical imaging application or a biological sample (such as a blood test).

Recent research points towards a particular protein (referred to as GPNMB) that could be a potential biomarker for a specific subtype of Parkinson’s.

In today’s post, we will review some of the research on this topic and consider how a biomarker could potentially be used in Parkinson’s research.

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Source: TED

Back in 2016, some researchers reported something interesting.

They had been investigating cells collected from people with a condition called Gaucher disease (Pronounced: ‘Go-Shay’; don’t ask – we’ll discuss what it is in a moment, just let me get the intro out of the way). Specifically, the scientists were seeking potential biomarkers for Gaucher disease… and they might have found one.

Here is their report:

Title: Elevation of glycoprotein nonmetastatic melanoma protein B in type 1 Gaucher disease patients and mouse models.
Authors: Kramer G, Wegdam W, Donker-Koopman W, Ottenhoff R, Gaspar P, Verhoek M, Nelson J, Gabriel T, Kallemeijn W, Boot RG, Laman JD, Vissers JP, Cox T, Pavlova E, Moran MT, Aerts JM, van Eijk M.
Journal: FEBS Open Bio. 2016 Jul 30;6(9):902-13.
PMID: 27642553                 (This report is OPEN ACCESS if you would like to read it)

In the study, the researchers collected cells from the spleen of an individual with Gaucher disease and looked for proteins in the cells that were higher than normal.

They found glycoprotein non-metastatic melanoma protein B (GPNMB, also known as osteoactivin) was ridiculously high. Off the charts high. They then compared GPNMB levels in blood samples collected from 59 people with Gaucher disease and 20 healthy controls. As you can see in the graph below, GPNMB levels were on average 25‐fold higher in all of the 59 people with Gaucher disease (Note: the Y axis is logarithmic):

Source: PMC

Interestingly, when the individuals with Gaucher disease started the standard treatment for the condition, the levels of GPNMB collectively dropped:

Source: PMC

And this result has been independently validated (Click here to read that report). The second study used a larger cohort of individuals with Gaucher disease (155 patients) and they found a >15-fold elevation of GPNMB in the blood of this group (compared to controls). And again these high levels were reduced when the Gaucher group started treatment:

Source: PMC

A third study found that GPNMB levels in the brains of a mouse model of Gaucher disease correlated with disease severity in the mice, and also reported elevated GPNMB levels in brain samples from patients with Gaucher disease.

All of the research groups concluded that their data supports the potential utility of GPNMB as a biomarker of Gaucher disease.

Great! But what is Gaucher disease and why is this on a website for Parkinson’s research?

Continue reading “G.P.N.M.B”

Does immunotherapy need therapy?

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Over the last decade, a large number of clinical trials involving immunotherapy have been conducted in the field of Alzheimer’s research. The overall success rate of these studies has not been encouraging.

Immunotherapy involves artificially boosting the immune system so that it targets of particular pathogen – like a rogue protein in the case of Alzheimer’s – and clears it from the body.

Recently, preclinical research has pointed to several possible reasons why this approach may be struggling in the clinical trials, and potential solutions that could be explored.

In today’s post, we will review two research reports and consider how this applies to Parkinson’s research.

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Immune cells (blue) checking out a suspect cell. Source: Lindau-nobel

Immunotherapy is a method of boosting the body’s immune system to better fight a particular disease. Think of it as training the immune cells in your body to target a particular protein.

The approach involves utilising the immune system of your body, and artificially altering it to target a particular protein/disease-causing agent that is not usually recognised as a pathogen (a disease causing agent).

It is truly remarkable that we have gone from painting on cave walls to flying helicopters on Mars and therapeutically manipulating our body’s primary defense system.

Immunotherapy is potentially a very powerful method for treating a wide range of medical conditions. To date, the majority of the research on immunotherapies have focused on the field of oncology (‘cancer’). Numerous methods of immunotherapy have been developed for cancer and are currently being tested in the clinic (Click here to read more about immunotherapy for cancer).

Many approaches to immunotherapy against cancer. Source: Bloomberg

Immunotherapy has also been tested in neurodegenerative conditions, like Alzheimer’s and more recently Parkinson’s. It typically involves researchers carefully designing antibodies that target a rogue protein (like beta amyloid in Alzheimer’s and alpha synuclein in Parkinson’s) which begin to cluster together, and this aggregation of protein is believed to lead to neurotoxicity.

Source: RND

What are antibodies?

Continue reading “Does immunotherapy need therapy?”

Monthly Research Review – May 2021

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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 May 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during May 2021?

In world news:

May 5th – Tech company SpaceX successfully flew and landed their Starship prototype for the first time:

May 9th – The 100th anniversary of the birth of Sophie Scholl (Click here to learn more about her)

 

May 10th – A pan-coronavirus mRNA nanoparticle vaccine with activity against all major SARSCoV2 variants was described in the science journal ‘Nature’, showing potent effect in non-human primates (Click here to read more about this).

May 14th – The China National Space Administration landed its Zhurong rover at Utopia Planitia on Mars, making China the fourth country to land a spacecraft on the planet and the second to land a rover (Click here to read more about this).

May 26th – Oil company Shell became the first company to be legally mandated to align its carbon emissions with the Paris climate accord, following a landmark court ruling in the Netherlands (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 May 2021, there were 911 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5,459 for all of 2021 so far). 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

Continue reading “Monthly Research Review – May 2021”

Denali’s Phase I results

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Leucine-rich repeat kinase 2 (or LRRK2) is a large, multi function protein that is associated with Parkinson’s. People with genetic variations in the region of DNA that provides the instructions for making LRRK2 protein have a higher risk of developing the condition.

In many cases of Parkinson’s, LRRK2 can become hyperactive. Researchers and biotech companies have been striving to identify drug-like molecules that can dampen down this hyperactivity in the hope of slowing down the progression of Parkinson’s.

One of the leading biotech firms in this area of research is Denali Therapeutics, and recently the company has provided some updates on their progress.

In today’s post, we will discuss what LRRK2 is, we will look at what Denali have achieved thus far, and we will review what the company has recently announced.

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Source: Denali

A presentation was given at the UBS 2021 Global Healthcare Virtual Conference this week by representatives from Denali Therapeutics.

The slide deck (which can be found here on the company’s website) touched on multiple lines of active research for the company, including their active clinical trial programs:

  • DNL310 (ETV:iduronate-2-sulfatase (IDS) for Hunter syndrome), which has expanded testing in Phase 1/2 based on positive interim data
  • DNL343 (EIF2B activator indicated for ALS), which has had positive interim Phase 1 data, and the company is planning a Phase 1b study in ALS (Click here to read a recent SoPD post on EIF2B activation)
  • DNL788 (RIPK1 inhibitor targeted at ALS, Alzheimer’s, & Multiple Sclerosis … I’m really curious, why not PD?!?), which is in ongoing Phase 1 studies in healthy volunteers (in collaboration with Sanofi)
  • DNL758 (aka SAR443122; another RIPK1 inhibitor targeted at inflammation), currently recruiting participants for a Phase 2 study of lupus & in Phase 1 for COVID-19 lung disease (again in collaboration with Sanofi)

Source: Denali

But of particular interest to us here at SoPD HQ were the slides on their LRRK2 inhibitor clinical trial data.

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.

Ex-Genentechers. Source: Medicalstartups

Although they have product development programs for other condition (such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease), Parkinson’s is definitely one of their primary indications of interest.

The company has been leading the charge in the development of LRRK2 inhibitors as a potential therapeutic class for Parkinson’s and they have recently made some big announcements.

What are LRRK2 inhibitors?

Continue reading “Denali’s Phase I results”

Unmasking LRRK2 and GBA

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Connecting genetics and biology is complicated. Researchers around the world have struggled to determine what each functional region of DNA is doing individually, let alone in combination with other regions.

And sometimes when the output of combinations is examined, the results can be unexpected.

Recently, researchers looked at the consequences of having a particular combination of Parkinson’s-associated risk factors… and they were rather surprised by the results

In today’s post, we will review the report presenting their results and consider the potential implications of the findings.

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Bragging rights. Source: Howstuffworks

A while back, I became a little obsessed with peacock feathers.

I didn’t start collecting them and wearing them on Saturday night or anything like that. Rather, I just got really fascinated with how they develop. Each individual feather, that is.

I mean, look at them:

Source: Dreamingandsleeping

Like all organisms, they are wondrous feats of nature and biology – particularly the jewel-toned ocelli (plural) or eyespots (the vivid circular patterns that seem evenly spread along each feather).

Each ocellus (singular) is created via a combination of individual strands of the larger feather. And each strand is further made up of tiny individually coloured segments. When you get really up close and personal with those eyespots, they look like this:

Source: Wired

My obsession centered around “the how”.

How does each strand of the feather know when to start some blue or gold colouration (and when to stop) along those strands? And how do the individual strands coordinate and match up so perfectly to create the marvelous image of the ocellus?

This type of question applies to many areas of biology (for example, how does a regenerating tail of a gecko know when to stop growing?), but remember that at the end of each mating season, the peacock sheds (or molts) its feathers. So these carefully coordinated feathers have to re-grow each year!

Tell me that that is not remarkable.

Remarkable, but what does this have to do with Parkinson’s?

Continue reading “Unmasking LRRK2 and GBA”

Monthly research review – April 2021

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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 April 2021.

The post is divided into 10 parts based on the type of research:

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So, what happened during April 2021?

In world news:

April 4th

 

April 15th – Investigators in China and the United States reported the injection of human stem cells into primate embryos, to grow chimeras for up to 20 days (and the world asked “Why?!? What was the point?!?” – click here to read the report and click here to read the press summary).

April 18th – The Super league! (Just a really dumb idea – basically, when rich people have more dollars than sense)

April 19th – “117 years after the Wright brothers succeeded in making the first flight on our planet, Nasa’s Ingenuity helicopter has succeeded in performing this amazing feat on another world” – Thomas Zurbuchen, Nasa’s associate administrator for science

April 21st – No Super League! Following an outcry from football fans and the withdrawal of the English clubs, the Super League was placed “on standby” (yeah, good luck with that).

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

In April 2021, there were 1,099 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (4,548 for all of 2021 so far). 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

Continue reading “Monthly research review – April 2021”

UCB at ANN looks A-OK

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Alpha synuclein is one of the most common proteins in our brains and it has long been associated with Parkinson’s. The protein appears to clump together forming dense clusters ( or “aggregates“) in the Parkinsonian brain, and this may be related to the progressive neurodegeneration.

Researchers have been desperately seeking small molecules that will break up (or dissociate) these aggregates in the hope that it will slow down the progression of PD and allow neurons to return to health.

One example of such a molecule is UCB0599, which is being clinically developed by the pharmaceutical company UCB. This week, UCB presented the first clinical results for UCB0599 from their Phase I trial.

In today’s post, we will look at what alpha synuclein is, review what is known about UCB0599, discuss the results of the study, and consider what comes next.

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Source: AAN

Last week at the 2021 American Academy of Neurology virtual meeting a poster was presented by the pharmaceutical company UCB.

Here at SoPD HQ, we have been eagerly awaiting these results.

They were the findings from the first Phase I clinical trial of a new molecule called UCB0599.

What is UCB0599?

UCB0599 is a brain-penetrant, oral small molecule alpha-synuclein misfolding inhibitor.

What does that mean?

Continue reading “UCB at ANN looks A-OK”

ISRIB: The ISR InhiBitor

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In December 2020, a research paper was published that drew a lot of attention.

It involved a molecule that reversed memory deficits in aged mice – even weeks after treatment has stopped.

The treatment involved inhibition of the integrated stress response.

In today’s post, we will explore what the integrated stress response is, review the data presented in new report, and consider what might happen next with this line of research (and be warned, there is quite a bit of biology to kick things off).

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Title: Small molecule cognitive enhancer reverses age-related memory decline in mice.
Authors: Krukowski K, Nolan A, Frias ES, Boone M, Ureta G, Grue K, Paladini MS, Elizarraras E, Delgado L, Bernales S, Walter P, Rosi S.
Journal: Elife. 2020 Dec 1;9:e62048.
PMID: 33258451                  (This report is OPEN ACCESS if you would like to read it)

This report was published in December 2020.

It starts with a quote:

Of the capacities that people hope will remain intact as they get older, perhaps the most treasured is to stay mentally sharp” (Source)

The report then proceeds to describe an experiment in which a small drug-like molecule reverses memory deficits in aged mice, even weeks after treatment has stopped.

Wow! What was the treatment?

The molecule is an ‘integrated stress response‘ (or ISR) inhibitor that has conveniently been called ISRIB (or ISR InhiBitor).

What is ISR and why would the researchers be inhibiting it?

Continue reading “ISRIB: The ISR InhiBitor”

500

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I started writing about the research being conducted in Parkinson’s in 2014. 

If I’m honest, it was simply an experiment. Having failed to write the next great kiwi novel (think Katherine Mansfield, Margaret Mahy, Witi Ihimaera, Eleanor Catton, and most recently Rose Carlyle), to distract myself I started playing around with science writing to see if I liked it.

And what do ye know: I did

One thing led to another… and now there’s 500 posts on this thing called “The Science of Parkinson’s” (Click here for the full list). 

In today’s post, we will revisit some of the key moments and thoughts on that journey.

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MOMENT OF CONCEPTION

The Science of Parkinson’s began life in the clinic room in the photo above.

It is clinic room 1 at the Brain Repair Centre at the University of Cambridge.

Back in 2014, yours truly had been working as a postdoctoral research scientist in Prof Roger Barker‘s lab, and (this will sound cliché, but) after almost 15 years of researching the biology of the Parkinson’s, I realised that I didn’t have much practical experience with the disease itself. Kind of like a taxi driver who thinks he has memorised all the roads, but has never actually climbed behind the wheel and interacted with a stranger wanting to be driven somewhere.

So I volunteered to help out in the clinic once or twice a week, doing some of the cognitive assessments.

It was straight forward work – leading folks through the various standardised tests – but the experience was extremely enlightening. Not just because one saw the heterogeneity of cases and the impact that the condition has on a human body (over time, with periodic visits), but also the human side of the whole beastly thing. You met and got to know the people affected and their families. You learnt their stories and listened to their lived experience of PD. It was a fascinating experience – one which further energized my efforts in the lab.

Everything had been going smoothly for about 8-9 months…

And then Martin Taylor walked in.

Continue reading “500”