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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”

Prevail lands on a Lilly pad

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2020 has been a dreadful year for most of the world – burdened by the outbreak and consequences of COVID-19. Despite this, there has been a steady stream of biotech acquisitions related to Parkinson’s which have helped to keep morale high in the PD research community.

In October alone, we saw the Portuguese pharmaceutical company Bial purchase GBA-associated Parkinson’s biotech firm Lysosomal Therapeutics (Click here to read more about this) and the acquisition of the inflammasome-focused biotech firm Inflazome was being bought by Roche (Click here to read more about this).

Today brought news of yet another pharmaceutical company – this time Eli Lilly purchasing a Parkinson’s-focused biotech company (Prevail Therapeutics).

In today’s post, we will explore what Prevail Therapeutics does, why Eli Lilly might be so interested in this company, and why it could be an encouraging move for individuals with a sub-type of Parkinson’s.

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Colonel Eli Lilly. Source: SS

The civil war veteran, Colonel Eli Lilly started his pharmaceutical career in a drug store in Greencastle (Indiana) in 1869.

Several years later (in 1873) he shifted into the manufacturing of pharmaceuticals (in association with John F Johnston). Two years after that, Lily disolved their partnership, sold his assets, and used the proceeds to set up “Eli Lilly and Co” in Indianapolis.

Source: Wikimedia

He started the company in a rented building on the 10th May, 1876. He was 38 years old, with working capital of $1400 and just three employees. The first medicine that he produced was quinine – a drug used to treat malaria.

Since that humble start, the company (now more commonly known as just “Lilly”) has grown to become one of the 20 largest pharmaceutical companies in the world (Source), with offices in 18 countries and products sold in 125 countries (Source).

Lilly was the first company to mass-produce the polio vaccine and it was also one of the first pharmaceutical companies to produce human insulin using recombinant DNA. Lilly is currently the largest manufacturer of psychiatric medications, including Prozac (Source).

Today, the company employs approximately 38,000 people worldwide, and operates through two key business divisions:

  • Human Pharmaceutical Products, which involves the production and sale of prescription medications in the fields of endocrinology, oncology, cardiovascular health, and neuroscience
  • Animal Health Products, comprising the development and sale of treatments for domestic and farm animals

This is all very interesting, but what does any of it have to do with Parkinson’s?

This week the biotech world was alerted to the news that Eli Lilly was purchasing a biotech company that is focused on developing a novel treatment for a subtype of Parkinson’s.

That company is called Prevail Therapeutics.

What does Prevail Therapeutics do?

Continue reading “Prevail lands on a Lilly pad”

GBA: Wider regulation = wider implications

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Tiny variations our DNA can have a significant impact on our lives.

For the last 20 years, Parkinson’s researchers have been collecting data highlighting ‘genetic risk factors’ that are associated with increasing one’s risk of developing the condition.

More recently, however, these same scientists have started shifting their attention to the factors that modulate these genetic risk factors – and some of those influences are also genetic.

In today’s post, we will look at new research exploring genetic variations that influence the effect of the Parkinson’s-associated GBA genetic variants, and discuss why this research has huge implications not only on how we conduct clinical trials, but also on how we will treat Parkinson’s in the future.

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Prof Craig Venter. Source: ScienceMag

In June 2000, when the results of the first human genome sequencing were announced during a ceremony at the White House, the DNA sequencing pioneer Prof Craig Venter observed that “The concept of race has no genetic or scientific basis“.

He was suggesting that due to genetic variations among human individuals and populations, the term ‘race’ cannot be biologically defined. There was simply no evidence that the broad groups we commonly refer to as “races” have any distinct or unifying genetic identities (Click here for interesting additional reading on this).

Source: Phillymag

Prof Venter’s words were a powerful statement regarding the incredible variability within our genetic make up.

And that variability is even more remarkable considering that we are all 99.9 percent genetically identical.

So how do we explain the variability then?

Continue reading “GBA: Wider regulation = wider implications”