Tagged: Parkinsons

EuPaTh: The Italian connection

 

The SoPD has a policy of not advertising or endorsing products/services.

This rule is in place to avoid any ethical/conflict of interest situations. It does little, however, to stop folks from bombarding the comments sections with links for wondrous magical cures which probably involve more ‘magical’ than actual cure.

Having said all that, every now and then I find or read about something that I think may be of interest to readers. In many of those cases, I can not vouch for the information being provided, but where I think there is the potential for readers to benefit, I am happy to take a chance and share it.

Today’s post is all about one such case: The European Parkinson Therapy Centre

 


Until very recently, I was working in Parkinson’s research centre in Cambridge (UK).

I conducted both lab- and clinic-based research on Parkinson’s in the lab of Prof Roger Barker. And it was in the clinic – several years ago – that I started hearing about a mysterious place that was not offering ‘to cure’ people of Parkinson’s, but rather helping them to live a better life with the condition.

Initially it was just a trickle of questions:

“Have you ever heard of this therapy place in Europe for people with Parkinson’s?” (“Nope, sorry” was my response).

But then an individual came in for their assessment, and spoke with tremendous enthusiasm about their own personal experience of visiting “this wonderful place in Italy” (“Sounds very interesting,” was my response, “Tell me more“).

Gradually, more and more people started sharing their own stories with me (both in the clinic, at support group meetings, and via correspondence to the SoPD website) about the place in Italy. And eventually it all led to me making some inquiries about the European Parkinson Therapy Centre.

What is the European Parkinson Therapy Centre?

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The lipidomics of Parkinson’s

 

Lipids are ‘waxy’ molecules that make up a large proportion of your brain and they play very important roles in normal brain function. For a long time researchers have also been building evidence that lipids may be involved with neurodegenerative conditions as well.

Recently, new research was presented that supports this idea (in the case of Parkinson’s at least), as two research groups published data indicating that certain lipids can influence the toxicity of the Parkinson’s associated protein alpha synuclein.

One of those research groups was a biotech company called Yumanity, and they are developing drugs that target the enzymes involved with the production of the offending lipids.

In today’s post, we will look at what lipids are, what the new research suggests, and discuss some of the issues that will need to be considered in the clinical development of these lipid enzyme inhibitors.

 


Yummy. Source: Healthline

Adherence to the ‘Mediterranean diet‘ has been associated with a reduced risk of developing Parkinson’s (Click here and here to read more about this), but no one has ever really explained why.

There has been the suggestion from some corners that this association may be due to the richness of monounsaturated fats in the foods generally included in this diet.

For example, olive oil is rich in monounsaturated fat.

What are monounsaturated fats?

Mmmm, before I answer that we need to have a broader discussion about “what is fat?“.

Fat is one of the three main macronutrients (carbohydrate and protein being the other two) that the body requires for survival.

Source: Visionpt

Fat serves as a ready source of energy for the body and can also provide insulation against cold temperatures or compression. All fats are derived from combinations of fatty acids (and also glycerol).

What are fatty acids?

A fatty acid is simply a chain of hydrocarbons terminating in a carboxyl group (having a carbonyl and hydroxyl group both linked to a carbon atom). Don’t worry too much about what that means, just understand that fatty acids are basically chains of hydrocarbons that look like this:

A chain of hydrocarbons ending in a carboxyl group (right). Source: Wikipedia

Fatty acids come in two forms:

  • Saturated
  • Unstaturated

In the case of a saturated fat, each carbon molecule in the chain of hydrocarbons is bonded to two other carbons by a single bond. Whereas in the case of a saturated fat, one or more carbon molecule in the chain of hydrocarbons is bonded to another carbon molecule by a double bond. For example:

Saturated fatty acids vs unsaturated fatty acids. Source: Medium

And unsaturated fatty acids can be further divided into:

  1. Monounsaturated fatty acids (or MUFAs) are simply fatty acids that have a single double bond in the fatty acid chain with all of the remainder carbon atoms being single-bonded.
  2. Polyunsaturated fatty acids (or PUFAs) are fatty acids that have more than one double bond.

Source: Medium

OK, but how might monounsaturated fats be involved with Parkinson’s?

That, dear reader, is the focus of numerous studies in the field of lipidomics.

What is lipidomics?

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Denali: Phase Ib clinical trial starts

 

Biotech firm Denali announced the dosing of the first person in their Phase Ib clinical study of their experimental treatment for Parkinson’s called DNL201.

DNL201 is an inhibitor of a Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (LRRK2).

In Parkinson’s, there is evidence that LRRK2 is over activate, and by inhibiting LRRK2 Denali is hoping to slow the progression of Parkinson’s.

In today’s post, we will discuss what LRRK2 is, what evidence exists for DNL201, and what the new clinical trial will involve.

 


 

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

And their target for therapeutic effect?

The Parkinson’s-associated protein called Leucine-rich repeat kinase 2 (or LRRK2).

What is LRRK2?

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Not bohemian, just ‘Rapsodi’

 

Moving forward into 2019 and beyond, we are going to be getting more sophisticated and targetted with our clinical trials for Parkinson’s. We are gradually moving away from the days when a drug was tested on anyone in the Parkinson’s-affected community, and heading for an age of sub-type specific treatments (Click here for a previous SoPD post on subtyping efforts for PD).

As part of this shift, there are a series of ongoing studies that are trying to identify not only the clinical & biological characteristics of those Parkinson’s sub-types, but also individuals who may already be in those groupings.

One such study is called “Rapsodi” – and it is focused on the identification of people with a particular genetic risk factor of PD – the GBA gene – who also demonstrate the early signs of Parkinson’s.

In today’s post, we will discuss what GBA is, how it is associated with Parkinson’s, and why the Rapsodi study is worthy of the PD community’s attention.

 


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Ambroxol. Source: Skinflint

The clinical trial of Ambroxol in Parkinson’s that has been conducted in London (UK) is close to announcing their final results. The Ambroxol study report should be published in early 2019.

What is the ambroxol study?

Started in February 2017, the Ambroxol study (named AiM-PDAmbroxol in Disease Modification in Parkinson Disease) is a phase IIA prospective, single-centre, open label clinical trial to evaluate the safety, tolerability and pharmacodynamic effects of Ambroxol in Parkinson’s (Click here to read more about this trial and click here for the press release announcing the start of the study).

This trial, which is funded by the Cure Parkinson’s Trust and the Van Andel Research Institute (USA), has been conducted at the Royal Free Hospital in London (UK). The study has involved 20 people with Parkinson’s self-administering Ambroxol (in 60 mg per tablet) over a 6 month time frame. The participants were given 5 escalating doses of the drug for the first few weeks of the study (from 60 mg three times per day, gradually building up to 420 mg three times a day after the first month of the study).

But hang on a second. What is exactly is Ambroxol?

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Thyme to look east: Baicalein

 

Recently I wrote a post about research investigating an interesting compound called Epigallocatechin gallate (or EGCG – click here for that post). Several eagle-eyed readers, however, noted something interesting in the details of one of the research reports that was discussed in that post.

The study in question had used EGCG as a positive control for evaluating the ability of other compounds for their ability to inhibit the clustering of Parkinson’s-associated protein alpha synuclein.

But there was also a second positive control used in that study.

It is called baicalein.

In today’s post, we will discuss what baicalein is and what research has been done on it in the context of Parkinson’s.

 


Lake Baikal. Source: Audleytravel

Once upon a thyme, in a far away land, there was a mysterious little flowering plant.

The “far away land” was the southern parts of eastern Siberia.

And the flowering plant is Scutellaria baicalensis – which is more commonly referred to as Baikal skullcap.

What is Baikal skullcap?

Baikal skullcap is a perennial herb that is indigenous to Southern Siberia, China and Korea. For centuries, traditional Chinese medicine has used the dried roots – which is called huángqín (Chinese: 黄芩 or golden root) – for a variety of ailments.

Baikal skullcap. Source: Urbol

The plant grows to between 1-4 feet in height, with lance head-shaped leaves and blue-purple flowers. Baikal skullcap belongs to the same family of flowering plants (Lamiaceae) as thyme, basil, mint and rosemary.

For traditional Chinese medicinal use, the roots are usually collected in spring or autumn once the plant is more than 3-4 years old. They are dried and then used to treat hypertension, to reduce “fire and dampness”, and to treat prostate & breast cancers.

And one of the key constituents of Baikal skullcap (and huángqín) is a compound called baicalein.

What is baicalein?

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Monthly Research Review – November 2018

 

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 November 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 

 


So, what happened during November 2018?

In world news:

4th November – Kiwi Mike Lloyd finished his 10th New York marathon! Diagnosed with Parkinson’s 6 years ago, his story is truly inspiring – “To me it’s a celebration of what I can do, & what we can do as people, rather than what we can’t do”

Oh, and did I mention he’s also blind?

Click here to read more about his most recent marathon and click here to see his website.

6th November – Mining company BHP suspended all rail operations in Western Australia after a train (consisting of 4 locomotives & 268 wagons) ladened with iron ore travelled over 92km (57miles) with no driver on board. It was finally deliberately derailed by the authorities. And that’s not the only crazy story out of Australia this month – check out Knickers the giant steer!

 

9th November – Supermarket Iceland had their Christmas advert banned in the UK because it was “deemed to breach political advertising rules” (Can anyone please explain to me why? I quite liked it):

 

11th November – New Zealand space company ‘Rocket Lab‘ announced the successful orbital launch and deployment of customer satellites – their first commercial project, named ‘It’s Business Time’ – at 16:50 NZDT (03:50 UTC – Click here for the press release). Little old NZ punching above its weight yet again. The launch can be seen from 20 minutes into this video:

 

22nd November – Engineers at the Massachusetts Institute of Technology announced that they have developed a model aircraft with no moving parts that is capable of flight. The age of ionic wind has begun.

 

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

In November 2018, there were 762 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (7172 for all of 2018 so far – we should easily beat last years total of 7644). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 8 pieces of Parkinson’s news

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Gene therapy: VY-AADC01 vs AXO-Lenti-PD

 

Future generations may treat conditions like Parkinson’s with DNA rather than drugs. By manipulating the DNA within a given cell, researchers can cause that cell to generate proteins that they usually do not produce.

This technique is called gene therapy, and it is currently being clinically tested in people with Parkinson’s.

Recently, one biotech firm (Voyager Therapeutics) has provided new data on an ongoing clinical trial and another company (Axovant Sciences) has announced the initiation of a clinical study.

In today’s post, we will discuss what gene therapy is, evaluate what the first company has achieved, and compare it with the clinical trial that is just starting.

 


Source: 2018.myana

At the annual American Neurology Association (ANA) meeting this year, we got an update on an ongoing clinical trial for Parkinson’s being conducted by a company called Voyager Therapeutics.

The biotech firm presented data at the meeting regarding their gene therapy approach for Parkinson’s.

What is gene therapy?

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Targeting PDE1 for PD

 

Many novel therapies are currently being clinically tested in Parkinson’s, and this week we heard the results of one clinical trial which provided some very interesting news.

Intra-Cellular Therapies has been testing their drug, ITI-214 – which is a potent and selective phosphodiesterase 1 (PDE1) inhibitor. Inhibitors of PDE1 prevent the breakdown of protein called cyclic nucleotides (cAMP, cGMP).

The results of the Intra-Cellular Therapies clinical trial suggest that in people with Parkinson’s, the drug not only improves symptoms, but also reduces dyskinesias.

In today’s post we will discuss what PDE1 is, how PDE1 inhibitors work, and what the results of the clinical trial suggest.

 


Source: 2018.myana

Every year in October, the American Neurology Association (ANA) gather in one of the major US cities to share research regarding neurological condtions, like Parkinson’s. And while I did not attend the ANA meeting this year, I was keen to hear the results of one particular clinical study.

It was a trial conducted by a company called Intra-Cellular Therapies.

And they were presenting the results of a Phase I/II trial of their experimental drug ITI-214.

What is special about ITI-214?

ITI-214 is a Phosphodiesterase inhibitor.

What is a phosphodiesterase inhibitor?

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Grand times in Grand Rapids

 

During the last week of September, the Van Andel institute and the Cure Parkinson’s Trust held their annual Parkinson’s research meetings in Grand Rapids, Michigan. 

The meetings – the Linked Clinical Trials meeting, Grand Challenges in Parkinson’s, and Rallying to the Challenge – provided an opportunity for members of the Parkinson’s community (both researchers and advocates) to come together, share research/knowledge/experience, and discuss what needs to be done.

I attended the meetings this year for the first time.

In today’s post, I thought I would provide some feedback and share some of my thoughts on the meetings.

 


Jay Van Andel (left) and Rich DeVos. Source: Amwayconnections

The history of Amway is an interesting story.

One of ambition, determination, and a refusal to give up.

It begins with the two founders – Jay Van Andel and Rich DeVos – trying and failing to get seven different businesses off the ground before they eventually founded the multi-level marketing company that we know of as Amway.

Source: Wikipedia

One aspect of the story that many people do not know, however, is that for a decade before he passed away in 2004, Jay Van Andel lived with Parkinson’s.

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Monthly Research Review – September 2018

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 September 2018.

The post is divided into five parts based on the type of research (Basic biology, disease mechanism, clinical research, other news, and Review articles/videos). 


So, what happened during September 2018?

In world news:

September 2nd – A fire destroyed the National Museum of Brazil in Rio de Janeiro –  a “catastrophic loss of artifacts”.

Source: HuffPost

September 14th – Hurricane Florence made landfall in Wrightsville Beach (North Carolina), caused extensive damage and flooding throughout in the Carolinas.

Source: WPLG

September 17th – In an effort to study the hidden physical properties of electrons, Japanese researchers built the ‘most powerful magnet on Earth’ – a 1200 Tesla, 3.2 megajoules beast. The experiment was supposed to go off with a bang, but the ‘bang’ was slightly more than expected: it blew the door off the protective chamber holding the experiment!

September 21st – after a three year journey, the first rover of the Japanese Hayabusa2 spacecraft touched down on the surface of the asteroid Ryugu. A truly remarkable achievement.

Source: NYTimes (some amazing images on this link)

September 24th – Two reports were published – one in the journal Nature Medicine and another in the journal New England Journal of Medicine – describing the case of 29-year-old Jered Chinnock (who 5 years ago could not feel or move his body from the chest down) recovering the ability of assisted walking following spinal cord stimulation and intensive physical therapy.

September 28th – A magnitude 7.5 earthquake hit the island of Sulawesi (Indonesia), causing a tsunami and terrible destruction and loss of life.

Source: Australian

 

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

In September 2018, there were 841 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5978 for all of 2018 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

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