Tag: PPMI

The Rise of the Sartans?

~ Simon ~ 2 Comments

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Drug repurposing represents a more rapid way of bringing new treatments to the public than the traditional novel drug development route. It involves clinically testing therapies in new conditions for which they are not currently approved.

Researchers conduct large drug screening studies to identify agents that could be repurposed and basic science experiments can also provide data to support evaluating a particular class of drug in new medical conditions.

Recently, accumulating evidence has pointed towards a class of drugs called sartans as potential candidates for repurposing for Parkinson’s. 

In today’s post, we will discuss what sartans are and review some of new studies suggesting the case for support.

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The sartan family photo. Source: MDPI

The “Sartans” sound like an ancient Greek tribe or Scottish clan.

Like a formidable horde of Viking brigands bearing down on some hapless village that is unaware it is about to be pillaged. One can imagine someone in said village suddenly seeing something out of the ordinary, realizes the impending disaster, and screaming “the sartans are coming! The sartans are coming!”

Source: Lifeinnorway

But the reality is something else entirely.

Sartans are in fact a class of drugs that are widely used for the treatment of hypertension (that is: high blood pressure). They are also administered to patients with certain heart or kidney diseases. The drugs work by blocking the function of a hormone.

That hormone is called angiotensin II.

Angiotensin II has a bad habit of causing your blood vessels (the tubes that transport blood around your body) to narrow. This action can increase your blood pressure and force your heart to work harder. Not a good situation in terms of longevity.

And before we go any further it has to be said, like any marauding tribe, the sartans need to be treated with respect – they are powerful drugs and can do worse than simply making people feel dizzy if they lower the blood pressure too much.

Good to know. But what do sartans have to do with Parkinson’s?

Continue reading “The Rise of the Sartans?” →

Forget Special K, maybe focus on LysoK

~ Simon ~ 1 Comment

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Over the last 20 years, researchers have identified a number of genetic variations that can confer an increased risk of developing Parkinson’s. Tiny alterations in regions of DNA (called genes) – which provide the instructions for making a protein – can increase one’s chances of Parkinson’s.

A better understanding of the biological pathways associated with these genetic risk factors is opening up vast new areas of research.

Recently researchers have been exploring the biology behind one particular genetic risk factor – involving a gene called TMEM175 – and they have discovered something quite unexpected: While one genetic variation in the TMEM175 gene increases the risk of Parkinson’s, another variation reduces it.

In today’s post, we will explore the biology of TMEM175, review what the results of the new research indicate, and consider why these findings might be interesting in terms of potential future therapeutic targets.

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Wadlow (back left). Source: Telegraph

Robert Pershing Wadlow was always in the back of school photos.

Born February 22nd 1918, Wadlow’s birth certificate indicated that he was “normal height and weight“, but from that point onwards, there was nothing normal about his rate of growth.

By the time, Robert was 8 years old, he was taller than his father (he was 6 foot/183cm). And eight years later when he turned 16, Robert was 8 foot 1 (2.47 m)… and he was still growing.

Here is a picture of him with his family at 19 years of age:

Source: Businessinsider

Robert was the tallest person in recorded history, and at the time of his death – at the tragically young age of 22 – Robert was almost 9 feet tall (8 ft 11; 2.72 m)… and still growing.

His incredible growth was caused by a condition called hyperplasia of his pituitary gland. This condition that results in an overactive pituitary gland which causes an abnormally high level of the human growth hormone to be produced.

Source: Britannica

Human growth hormone (or somatotropin) is a peptide hormone that belongs to a much larger group of molecules that are referred to as growth factors.

In general terms, growth factors are small molecule that plays an important and fundamental role in biology. They stimulate cell proliferation, wound healing, and occasionally cellular differentiation.

And Robert’s story is an example of how powerful the effect these tiny molecules can have.

Growth factors are secreted from one cell and they float around in the extracellular world until they interact with another cell and initiate survival- and growth-related processes.

Source: Wikimedia

We have often discussed growth factors on this website in the past, with posts of growth factors like GDNF (Click here to read a SoPD about this) and CDNF (Click here to read a SoPD post on this). These discussions have largely focused on how growth factors could have neuroprotective and regenerative potential for Parkinson’s, stimulating survival and growth of cells.

Recently, however, new research has been published that demonstrates how some of these growth factors could be influencing an entirely different aspect of cellular biology that is connected to Parkinson’s: lysosomal function.

What is lysosomal function?

Continue reading “Forget Special K, maybe focus on LysoK” →

Yo DJ, stop mis-splicing

~ Simon ~ 4 Comments

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RNA – the usable copy of a section of DNA – has regions called introns that need to be removed before the RNA can be used for the production of protein. The process of removing introns is called splicing.

Recently researchers have noticed that a genetic mutation in a Parkinson’s-associated gene – called DJ-1 – affects the splicing of the associated RNA and this has serious consequences on the activity of the DJ-1 protein.

Interestingly, they were able to pharmacologically rescue the effect, and noticed that DJ-1 might not be the only Parkinson’s-associated gene affected by this splicing error.

In today’s post, we will discuss what splicing is, review the new research, and discuss the wider implications for the Parkinson’s community.

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Source: Wikibooks

Today’s post starts off with a definition:

Splice – /splʌɪs/; verb;
Meaning: “to combine, interweave”.
Origin: 16th century: probably from Middle Dutchsplissen,
Similar:  braid, plait, entwine, intertwine, interlace, knit
Additional/alternative meanings:
1.  (From the arts) When two pieces of recorded music – with a similar key and tempo – are combined:

2.  (From biology) The process that removes the intervening, non-coding sequences of genes (introns) from pre-mRNA and joins the protein-coding sequences (exons) together in order to enable translation of mRNA into a protein:

Ok, so the first alternative definition about music I understood and the video was helpful, but can you explain the second definition in more detail please?

Continue reading “Yo DJ, stop mis-splicing” →

On the hunt for biomarkers

~ Simon ~ 4 Comments

 

The monitoring and assessment of the symptoms/features of Parkinson’s is a big deal in the research community at the moment.

There is currently a mad hunt for ‘biomarkers’ – reliably measurable physical characteristics – that could help not only with the assessment of individuals living with the condition, but could also aid in the running of clinical trials by providing additional measures of efficacy/benefit.

Recently an interesting perspective was written by some of the leading researchers in this field.

In today’s post, we review what the perspective outlined, and we will discuss other aspects of the biomarker research that need to be considered by the wider Parkinson’s community.

 

Perspective. Source: Huffingtonpost

Scientific journals will often invite the research leaders in a particular field of investigation to write a brief journal article that deals with unique view of a common problem.

Articles of this nature are called ‘Perspectives‘.

And recently a very interesting perspective was published in the journal Science on the topic of biomarkers for Parkinson’s.

Title: Finding useful biomarkers for Parkinson’s disease
Authors: Chen-Plotkin AS, Albin R,….a lot of additional authors…, Zhang J
Journal: Science Translational Medicine, 15 Aug 2018, 10 (454), eaam6003.
PMID: N/A

This perspective included a rather long list of a ‘who’s-who’ of Parkinson’s researchers – both academic and industry. Even members of the Michael J Fox Foundation and Verily/Google Life Sciences were included.

The perspective sought to highlight ‘the “ecosystem” of shared biofluid sample biorepositories and data sets will focus biomarker efforts in Parkinson’s‘. It is a very enlightening read, one that begs for reader responses. But sadly the article is behind a ‘pay wall’, and so many in the Parkinson’s community won’t be able to provide any thoughts or feedback.

Shame.

But not to worry, we can discuss the matter here. And the best place to start that discussion is with the obvious first question:

What is a biomarker?

A biomarker is an objectively measurable physical characteristic associated with a condition. It is a biological component of a condition that correlates with that condition in some way. For example, the DaTscan brain imaging technique provides a ‘biomarker’ for Parkinson’s by measuring the amount of dopamine re-absorption in the brain. By labelling the dopamine neurons with a radioactive marker, we can quantify the levels of dopamine activity in a person.

An example of a DaTscan. Source: Cedars-sinai 

What did the perspective say about biomarkers for Parkinson’s?

Continue reading “On the hunt for biomarkers” →

Predicting subtypes of Parkinson’s

~ Simon ~ 9 Comments

Today’s post involves massive multidimensional datasets, machine learning, and being able to predict the future.

Sound interesting?

Researchers are the National Institute on Aging and the University of Illinois at Urbana–Champaign have analysed longitudinal clinical data from the Parkinson’s Progression Marker Initiative (PPMI) and they have found three distinct disease subtypes with highly predictable progression rates.

NOTE: Reading about disease progression may be distressing for some readers, but please understand that this type of research is critical to helping us better understand Parkinson’s.

In today’s post, we will look at what the researchers found and discuss what this result could mean for the Parkinson’s community.

Source: ScienceMag

Today I am going to break one of the unwritten rules of science communication (again) .

Until a research report has been through the peer-review process you probably should not be discussing the results in the public domain.

But in this particular case, the research is really interesting. And it has been made available on the OPEN ACCESS preprint depository website called BioRxiv.

Source: BioRxiv

I should add that this is not the first time we have discussed manuscripts on BioRxiv (Click here and here to read other post on Biorxiv manuscripts). We are regular rule breakers here at the SoPD.

So what does the new research investigate?

Continue reading “Predicting subtypes of Parkinson’s” →