The basket case

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One of the more interesting pieces of clinical trial news in 2020 was the publication of the results of a “basket study” for neurological conditions. This was a trial that involved a drug being tested on a selection of neurodegenerative conditions, rather than just one condition.

Between December 2013 to May 2017, researchers recruited a total of 29 individuals with Alzheimer’s, 14 with progressive supranuclear palsy (PSP) and 30 with corticobasal syndrome. These participants were intravenously injected with the same drug (TPI-287 – a microtubule stabilizer) once every 3 weeks for 9 weeks (with an optional 6-week open-label extension).

Although the findings of the study did not support further development of TPI-287 for tauopathies, the overall structure of the study represents an interesting example of how researchers are taking different approaches to investigating neurodegenerative conditions.

In today’s post, we will discuss novel clinical trial designs (“baskets and umbrella”) and other examples of research efforts to better understand neurodegeneration as a whole.

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Source: HuffPost

It was when my daughter turned 3 years old that the psychological warfare really started.

And I remember the moment of realisation very clearly: It began with her desire for a pet dog.

Up until that point in time, she had limited experience with dogs and her negotiation strategies centred solely around crying. I think she loved “the idea” of a dog, but she was generally quite timid around them. Regardless, she gradually began applying pressure (read: lots of crying) on us to get a dog.

And said pressure began to build rapidly (read: frequent episodes of lots of crying).

Source: Focus

Now my wife is definitely not a dog person (“wet, filthy, smelly things“). I on the other hand quite like dogs, but I was utterly, utterly, utterly opposed to getting one because I know full well who will be lumped with the mid-winter late night “walkies” two years down the line: me!

The pressure from our daughter continued to increase, however, until we finally had to sit down with her and explain that we were not going to be getting a dog. On the surface, it looked like she handled this news very well (that is to say: she did not cry). She simply accepted the situation, got up and left the room, saying “Ok”.

My wife and I looked at each other and thought “problem solved”.

The next morning, however, this picture was waiting for us on the kitchen table:

I kid you not.

That’s my daughter and her pet dog (“Linguine“) on the right, and I’m the big, cross-eyed, bad guy on the left.

Since that time the psychological manoeuvring has only become more sophisticated (the teenage years are still a few years away, but I am already absolutely terrified!).

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

Continue reading “The basket case”

The next killer APP: LRRK2 inhibitors?

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In Silicon valley (California), everyone is always looking for the “next killer app” – the piece of software (or application) that is going to change the world. The revolutionary next step that will solve all of our problems.

The title of today’s post is a play on the words ‘killer app’, but the ‘app’ part doesn’t refer to the word application. Rather it relates to the Alzheimer’s disease-related protein Amyloid Precursor Protein (or APP). Recently new research has been published suggesting that APP is interacting with a Parkinson’s disease-related protein called Leucine-rich repeat kinase 2 (or LRRK2).

The outcome of that interaction can have negative consequences though.

In today’s post we will discuss what is known about both proteins, what the new research suggests and what it could mean for Parkinson’s disease.


Seattle

Seattle. Source: Thousandwonders

In the mid 1980’s James Leverenz and Mark Sumi of the University of Washington School of Medicine (Seattle) made a curious observation.

After noting the high number of people with Alzheimer’s disease that often displayed some of the clinical features of Parkinson’s disease, they decided to examined the postmortem brains of 40 people who had passed away with pathologically confirmed Alzheimer’s disease – that is, an analysis of their brains confirmed that they had Alzheimer’s.

What the two researchers found shocked them:

PDAD

Title: Parkinson’s disease in patients with Alzheimer’s disease.
Authors: Leverenz J, Sumi SM.
Journal: Arch Neurol. 1986 Jul;43(7):662-4.
PMID: 3729742

Of the 40 Alzheimer’s disease brains that they looked at nearly half of them (18 cases) had either dopamine cell loss or Lewy bodies – the characteristic features of Parkinsonian brain – in a region called the substantia nigra (where the dopamine neurons are located). They next went back and reviewed the clinical records of these cases and found that rigidity, with or without tremor, had been reported in 13 of those patients. According to their analysis 11 of those patients had the pathologic changes that warranted a diagnosis of Parkinson’s disease.

And the most surprising aspect of this research report: Almost all of the follow up studies, conducted by independent investigators found exactly the same thing!

It is now generally agreed by neuropathologists (the folks who analyse sections of brain for a living) that 20% to 50% of cases of Alzheimer’s disease have the characteristic round, cellular inclusions that we call Lewy bodies which are typically associated with Parkinson disease. In fact, in one analysis of 145 Alzheimer’s brains, 88 (that is 60%!) had chemically verified Lewy bodies (Click here to read more about that study).

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A lewy body (brown with a black arrow) inside a cell. Source: Cure Dementia

Oh, and if you are wondering whether this is just a one way street, the answer is “No sir, this phenomenon works both ways”: the features of the Alzheimer’s brain (such as the clustering of a protein called beta-amyloid) are also found in many cases of pathologically confirmed Parkinson’s disease (Click here and here to read more about this).

So what are you saying? Alzheimer’s and Parkinson’s disease are the same thing???

Continue reading “The next killer APP: LRRK2 inhibitors?”