Category: MajorTom

Mo better for TEVA with Modag?

~ Simon ~ 4 Comments

 

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This week the pharmaceutical company TEVA Pharmaceuticals Industries Ltd has announced a deal with a small German biotech firm called MODAG.

The two companies are forming a strategic collaboration on the exclusive worldwide licensing and development of MODAG’s lead compound anle138b.

Anle138b is a small molecule inhibitor of the believed to be toxic forms of the Parkinson’s-associated protein alpha synuclein.

In today’s post, we will discuss what is known about anle138b and the implications of this new partnership.

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Source: SLE

In 1901, Haim Salomon and his brother-in-law Moshe Levin established a small wholesale drug business, near the Nablus Gate in Jerusalem. They called it “Salomon and Levin”. A few years later, Yitzhak Elstein, another of Haim Salomon’s brothers-in-law, joined the firm and they changed the name of the company to SLE – Salomon Levin and Elstein.

Source: SLE

From these humble beginning, grew a pharmaceutical juggernaut that we know today as TEVA Pharmaceuticals.

TEVA – meaning “Nature” in Hebrew – is now an international producer of pharmaceutical agents, with 40,000 employees working across 65 manufacturing facilities in more than 30 countries. The company has a portfolio of more than 3,500 medicines, and they produce approximately 85 billion tablets and capsules per year (Source).

Does TEVA produce any drugs for Parkinson’s?

Yes, Azilect (rasagiline) – an approved monoamine-oxidase B inhibitor for the treatment of Parkinson’s – was developed by Teva Pharmaceuticals.

In addition, they are actively developing novel therapies. And this week they signed a really interesting deal to collaborate with a small German biotech company called MODAG.

What does MODAG do?

Continue reading “Mo better for TEVA with Modag?” →

Repurposing bumetanide for Alzheimer’s

~ Simon ~ 5 Comments

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Bumetanide (Bumex) is a diuretic drug (a medication that removes water, by increasing the production of urine). It is used to treat swelling caused by heart failure or liver or kidney disease. It is a widely used drug that has been well characterised in clinical use.

Recently researchers conducted a screening study to identify clinically available agents that might be useful in the treatment of the cognitive decline associated with a genetic risk factor for Alzheimer’s: APOE4 

The top drug identified in their study was bumetanide.

In today’s post we will discuss what APOE4 is, we will review the results of the new study, and we will look at why these findings could be interesting for Parkinson’s.

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Source: Pharmacysafety

Many years ago, I was at a patient-research interaction event and a world-leading genetics researcher was asked by someone in the audience if they had had their DNA sequenced.

They said ‘no‘.

The person asking the question frowned and asked ‘why not? You have all the technology and knowledge – don’t you want to know more about yourself?‘

The researcher replied “No. Having your DNA sequenced should not be taken lightly. You might learn stuff about yourself that you don’t want to know”

They used the example of possibly being an APOE4 carrier (who have a higher risk of cognitive decline during aging). The geneticist declared that they would rather not know that kind of information for fear of the impact that it could have on their life.

The questioner respected the honest answer and the conversation that followed was really interesting. More recently, however, as we have learned more about APOE4 and new drugs are being targeted at this risk factor, I have often wondered if their decision would still stand. Are we approaching an age when we might want to know if we are APOE4 carriers?

Hang on a moment. What is this APOE4 thing?

Continue reading “Repurposing bumetanide for Alzheimer’s” →

Making a (G)case for quetiapine

~ Simon ~ 8 Comments

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Drug repurposing (repositioning, reprofiling or re-tasking) is a strategy of identifying novel uses for clinically approved (or experimental) drugs that fall outside the scope of the original medical indication.

Many drug repurposing efforts have started with screening experiments, looking for drugs with certain properties.

Recently, researchers conducted a drug repurposing screening experiment for molecules that enhance a Parkinson’s protein (called GCase) and they found an interesting result: the antipsychotic medication quetiapine.

In today’s post, we will explain what GCase does, review what the new study found, and consider what could happen next.

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At the recent “Rallying to the Challenge” meeting (which was conducting in parallel with the Van Andel Institute‘s “Grand Challenges in Parkinson’s Disease“), I was asked by Cure Parkinson’s to present on why the biology surrounding genetic risk factors – like variation in the GBA and LRRK2 genes – are important targets for potential therapeutic intervention in Parkinson’s (my presentation starts at 2 hours & 10 minutes into the video above).

Specifically, I was asked to discuss why they are important targets not just for individuals carrying the genetic variations in these genes, but for the wider Parkinson’s community in general. And it is a good question.

How could inhibitors of LRRK2 or enhancers of GCase activity possibly be useful to individuals with idiopathic (spontaneous or not associated with a genetic risk factor) Parkinson’s?

My answer was rather simple.

What was it?

Continue reading “Making a (G)case for quetiapine” →

Farnesol: The farnesylator of PARIS

~ Simon ~ 12 Comments

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A build up of “PARkin Interacting Substrate” (or PARIS) protein has been proposed as one potential mediator of the pathology observed in some cases of Parkinson’s. The accumulation of this protein leads to the inhibition of a key protein called PGC-1α, which is a neuroprotective protein that helps to keep cells alive.

For sometime, researchers have been searching for molecules that can act as inhibitors of PARIS, in the hope that blocking PARIS would allow PGC-1α to act freely. Such an agent could have potential as novel treatment for Parkinson’s.

This week a research report was published that describes one possible PARIS inhibitor. It is called farnesol.

In today’s post, we will look at the biology behind PARIS, review the new report, and discuss what exactly is known about farnesol.

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Pont Royal et Musée d’Orsay. Source: Wikipedia

Paris has a special place in my heart for several reasons.

The main one: I proposed to my wife there on the Pont Royal.

We had planned a day out in London, but once we got down to Waterloo “for lunch at a special restaurant“, I surprised her with two Euro Star tickets and we were off on the train for Paris – just like that (I might look the hardened tough guy on the outside, but deep down I am really just a tragic romantic).

And that night, after “dinner at a special restaurant” shortly before 10pm as we were crossing the middle of the Pont Royal, and a small miracle occurred: the traffic lights stopped traffic in both directions.

Source: Pixels

Seizing our chance moment alone, I dropped to one knee and asked (read: begged).

Now, if she had said ‘no thanks‘, I had a back up plan: Jump over the side of the bridge, float down the Seine some ways, climb out and then join the Foreign Legions the next day as a mute (“je suis muet”).

But she didn’t say no (let’s call that the second small miracle) and thankfully for my fragile ego’s sake there wasn’t a lengthy deliberation.

When the traffic lights changed and traffic started to flow again, we received some enthusiastic honks of the klaxons (horns) as I got up and we headed off to alert our parents. It was a really nice moment.

I was recalling this moment, this week when a different type of Paris was being discussed in the news.

What do you mean “a different type of Paris”?

Continue reading “Farnesol: The farnesylator of PARIS” →

The Bluerockers have started

~ Simon ~ 2 Comments

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On the 8th June, BlueRock Therapeutics put out a press release announcing that the first participant in their Phase I clinical trial of cell transplantation for Parkinson’s had been dosed (Click here to read the press release).

The initiation of this clinical trial by the company is a major step forward for them and for the wider field of regenerative therapies.

In today’s post, we will look at what cell transplantation is, recent developments in clinical trials, and what the immediate future holds. 

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Source: The Scientist

Here on the SoPD, we work around the idea that any “curative therapy” for Parkinson’s is going to require three core components:

  1. A disease halting mechanism
  2. A neuroprotective agent
  3. Some form of restorative therapy

Parkinson’s is a progressive neurodegenerative condition, meaning that symptoms are gradually going to get worse over time. Thus, the first and most critical component of any ‘cure’ for Parkinson’s involves a treatment that will slow down or halt the progression of the condition.

Once such a therapy has been identified, it will be necessary to rejuvenate and protect the remaining cells. So, some form of neuroprotective therapy that can help bring sick or dying cells back to life will be required.

Such a treatment will also provide a nurturing environment for the third part of the ‘cure’: A restorative treatment. New cells will be required to replace the lost function.

Now, the bad news is (as far as I am aware) there is no single treatment currently available (or being tested) that can do all three of these things. By this I mean that there is no “disease halting mechanism” therapy that can also replace lost brain cells. Nor is there a restorative therapy that stop the progression of the condition.

That statement can obviously be read as terrible news, but it shouldn’t.

Let me explain:

Continue reading “The Bluerockers have started” →

The Anavex results

~ Simon ~ 8 Comments

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This week some encouraging clinical trial results were announced by a biotech firm called Anavex Life Sciences.

The company had been testing their lead experimental therapy – a Sigma-1 receptor agonist called ANAVEX2-73 (also known as blarcamesine) – in 132 people with Parkinson’s disease dementia over a 14 week period.

The results are rather encouraging: significantly positive outcomes in both cognitive and motor symptoms.

In today’s post, we will explain what exactly “Sigma-1 receptor agonist” means, discuss what Parkinson’s disease dementia is, and review what we currently know about the results of the trial.

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Source: Pumpingmarvellous

A lot of clinical trials for disease modification in Parkinson’s are focused on targeting well known proteins that are believed to be associated with underlying biology of the condition, such as alpha synuclein, LRRK2, and GBA. We discuss these on a regular basis here on the SoPD.

There are, however, a large number of trials investigating less well known targets.

And this week we received news that one of these clinical trials had some positive results.

Source: Thestreet

The study was conducted by the biotech company Anavex Life Sciences and it involved their lead experimental therapy ANAVEX2-73 (also known as blarcamesine).

ANAVEX2-73 is a Sigma-1 receptor agonist.

What does that mean?

Continue reading “The Anavex results” →

EJS-ACT PD

~ Simon ~ 10 Comments

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This week an announcement was made regarding The Edmond J. Safra Accelerating Clinical Treatments for Parkinson’s Disease (EJS-ACT PD) Initiative.

It is hoping to revolutionise the way clinical trials for potentially disease-modifying drugs for Parkinson’s are conducted.

The project is focused on the setting up a multi-arm, multi-stage (MAMS) platform for evaluating new therapies for PD.

In today’s post, we will discuss what MAMS trials involve and the current details of the EJS-ACT PD initiative.

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Source: Motionarray

This week I boarded a train for the first time in 16 months and made my way down to London. It felt a wee bit surreal.

I arrived at Liverpool street station and was immediately shocked by the lack of crowds, the lack of face masks (seriously?!? I’ve had my two jabs as well, but I’m still wearing my mask – you are nuts if you don’t!), and the large number of empty shops. How the world has changed.

In the early morning light, I walked across central London towards St Pancras station – the weather was spectacular and it was an incredible pleasure to stroll through some old stomping grounds.

Source: Parksandgardens

At St Pancras station, I made my way to the enormous Francis Crick institute, where a group of Parkinson’s researchers and advocates were gathering for a really intriguing meeting.

Source: Timeshighereducation

What was the meeting about?

Continue reading “EJS-ACT PD” →

Unmasking LRRK2 and GBA

~ Simon ~ 4 Comments

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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” →

UCB at ANN looks A-OK

~ Simon ~ 3 Comments

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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” →

What is GDNF without RET?

~ Simon ~ 3 Comments

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Neurotrophic factors – like Glial cell line-derived neurotrophic factor (or GDNF) – hold great hope for regenerative therapy in Parkinson’s research. New research, however, indicates that simply injecting the protein into the brain may not be enough.

Scientists at Rush University Medical Center (in Chicago) conducted a postmortem analysis of brains from people who passed away with Parkinson’s and made an intriguing discovery.

They found that many of the remaining dopamine neurons appear to not be producing a protein called Ret, which is required for GDNF signaling. In addition, other components of GDNF signaling pathway were missing. 

In today’s post, we will review the background of this new study, outline what the study found, and discuss the implications of the research.

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GDNF. Source: Wikipedia

Glial cell line-derived neurotrophic factor (or GDNF) is a topic that gets a lot of reader attention on the SoPD. It is a tiny protein that holds great hope for the Parkinson’s community in terms of providing a potential neuroprotective and regenerative therapy.

GDNF is a type of neurotrophic factor, which are small naturally-occurring proteins that nurture neurons and support their growth. There are different kinds of neurotrophic factors, and the testing of some of them in preclinical models of Parkinson’s has generated encouraging results (particularly in the case of GDNF – click here to read a previous SoPD post on this topic).

But the translation of those initial results in cell culture and animal models of Parkinson’s has been difficult in clinical trials of neurotrophic factors.

This has led to many questions being asked within the research community about the nature of biological signaling pathways involved with neurotrophic factors and whether they might be affected in Parkinson’s.

The majority of the neurotrophic factors that have been tested in models of Parkinson’s and in clinical trials for Parkinson’s belong to a branch that requires the RET signaling pathway to be available to have their neuroprotective effect.

What is the RET signaling pathway?

Continue reading “What is GDNF without RET?” →