Tagged: Affiris

Prothena: Phase I results published

This week, biotech firm Prothena published the results of their Phase I safety and tolerance clinical trial of their immunotherapy treatment called PRX002 (also known as RG7935).

Immunotherapy is a method of artificially boosting the body’s immune system to better fight a particular disease. 

PRX002 is a treatment that targets a toxic form of a protein called alpha synuclein – which is believed by many to be one of the main villains in Parkinson’s. 

In today’s post, we will discuss what immunotherapy is, review the results of the clinical trial, and consider what immunotherapy could mean for the Parkinson’s community.


Source: uib

I have previously mentioned on this website that any ‘cure for Parkinson’s’ is going to require three components:

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

This week we got some interesting clinical news regarding the one of these components: A disease halting mechanism.

The Phase I results of a clinical trial being conducted by a company called Prothena suggest that a new immunotherapy approach in people with Parkinson’s is both safe and well tolerated over long periods of time.

The good folks at Prothena Therapeutics. Source: Prothena

What is immunotherapy?

Continue reading

A vaccine for Parkinson’s – the AFFiRiS update

This week Austrian biotech firm, AFFiRiS AG, made an announcement regarding their experimental immunotherapy/’vaccine’ approach for Parkinson’s.

In their press release, the company provided the results of a long-term Phase I clinical trial testing the tolerability and safety of their treatment AFFITOPE® PD01A.

The treatment was found to be safe and well-tolerated in people with Parkinson’s. But there was one sentence which was particularly intriguing in the press release regarding clinical symptoms.

In today’s post, we will discuss what is meant by ‘immunotherapy’, outline what this particular clinical trial involved, review the results, and explore what this could mean for the Parkinson’s community.


Source: uib

I have previously mentioned on this website that any ‘cure for Parkinson’s’ is going to require three components:

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

This week we got some interesting clinical news regarding the one of these components: A disease halting mechanism

Clinical trial results from Austria suggest that a new immunotherapy approach in people with Parkinson’s is both safe and well tolerated over long periods of time.

What is immunotherapy?

Continue reading

When SERCA goes berserker

In a recent SoPD post, we discussed the importance of calcium and looked at how it interacts with the Parkinson’s-associated protein alpha synuclein, affecting the function and clustering of that protein.

During the writing of that post, another interesting research report was published on the same topic of calcium and alpha synuclein. It involved a different aspect of biology in the cell – a structure called the endoplasmic reticulum – but the findings of that study could also explain some aspects of Parkinson’s.

In today’s post, we will review the new research report, consider the biology behind the findings and how it could relate to Parkinson’s, and discuss how this new information could be used.


The original berserker. Source: Wikipedia

I can remember my father often saying “If you kids don’t be quiet, I’ll go berserk!”

Growing up, I never questioned the meaning of the word ‘berserk‘.

I simply took it as defining the state of mindless madness that my dad could potentially enter if we – his off-spring – pushed him a wee bit too far (and for the record, Dad actually ‘going berserk’ was a very rare event).

My father. But only on the odd occasion. Source: Screenrant

But now as I find myself repeating these same words to my own off-spring, I am left wondering what on Earth it actually means?

What is ‘berserk‘?

Continue reading

BIIB054: An immunotherapy update

Immunotherapy is an experimental treatment that is being tested in Parkinson’s in the hope that it will be able to slow down the progression of the condition.

This week the Pharmaceutical company Biogen provided an update regarding their immunotherapy program for Parkinson’s.

It involves a drug called BIIB054.

In today’s post we will look at what BIIB054 is, how it works, and review the results of Biogen’s first clinical trial with this treatment.


This week the 2018 American Academy of Neurology ANN Annual Meeting is being held in Los Angeles (California). The meeting is an opportunity each year for researchers to meet and share new discoveries. A lot of neuroscience-focused biotech companies use the meeting to release new clinical trial results.

And this year one result in particular has been rather encouraging.

At 3:30pm on 24th April, the pharmaceutical company Biogen made a presentation entitled “Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of AntiAlpha-Synuclein Antibody BIIB054 in Patients with Parkinson’s Disease,” which provided some of the first insights into the companies immunotherapy program for Parkinson’s.

What is immunotherapy?

Continue reading

Alpha Synuclein: New Species

On this website, we regularly talk about a Parkinson’s-associated protein called Alpha Synuclein.

It is widely considered to be ‘public enemy #1’ in the world of Parkinson’s research, or at the very least one of the major ‘trouble makers’. It is a curious little protein – one of the most abundant proteins in your brain. 

But did you know that there are different ‘species’ of alpha synuclein? 

And recently researchers in Florida announced that they had identified an all new species of alpha synuclein that they have called “P-alpha-syn-star” or Pα-syn*.

In today’s post, we will discuss what is meant by the word ‘species’, look at the different species of alpha synuclein, and explore what this new species could mean for the Parkinson’s community.


 Source: Nationalgeographic

This microscopic creature is called Macrobiotus shonaicus. 

Isn’t it cute?

The researchers that discovered it found it in a Japanese parking lot.

It is one of the newest species of life discovered to date (Click here for the research report). It is a species of Tardigrade (meaning “slow stepper”; also known as a water bear or moss piglet). And for the uninitiated: Tardigrade are remarkable creatures.

Tardigrade. Source: BBC

They measure just 0.5 mm (0.02 in) long, there are approximately 1,150 known species of them, and they have been around for a VERY long time – with fossil records dating back to the Cambrian period (500 million years ago).

The tree of life (try and find the dinosaurs). Source: Evogeneao

But most importantly, tardigrade are EXTREMELY resilient:

  • they are the first known animals to survive in hard vacuum and UV radiation of outer space. Some of them can withstand extreme cold – down to temperatures of −458 °F (−272 °C), while other species of Tardigrade can withstand extremely hot temperatures  – up to 300 °F (150 °C) (Click here to read more)
  • they can withstand 1,000 times more radiation than other animals (Click here for more on that)
  • some species of Tardigrade can also withstand pressure of 6,000 atmospheres (that is nearly SIX times the pressure of water in the deepest ocean trench – the Mariana trench! Click here for more on this)
  • They are one of the few groups of species that are capable of suspending their metabolism; surviving for more than 30 years at −20 °C (−4 °F – Click here to read about this)

They are utterly remarkable creatures.

Great, but what does this have to do with Parkinson’s? Continue reading

The road ahead: Parkinson’s research in 2018

The great ice hockey player Wayne Gretzky once said “A good hockey player plays where the puck is. A great hockey player plays where the puck is going to be” (the original quote actually came from his father, Walter). 

At the start of each year, it is a useful practise to layout what is planned for the next 12 months. This can help us better anticipate where ‘the puck’ will be, and allow us to prepare for things further ahead.

2017 was an incredible year for Parkinson’s research, and there is a lot already in place to suggest that 2018 is going to be just as good (if not better).

In this post, we will lay out what we can expect over the next 12 months with regards to the Parkinson’s-related clinical trials research of new therapies.


Charlie Munger (left) and Warren Buffett. Source: Youtube

Many readers will be familiar with the name Warren Buffett.

The charming, folksy “Oracle of Omaha” is one of the wealthiest men in the world. And he is well known for his witticisms about investing, business and life in general.

Warren Buffett. Source: Quickmeme

He regularly provides great one liners like:

“We look for three things [in good business leaders]: intelligence, energy, and integrity. If they don’t have the latter, then you should hope they don’t have the first two either. If someone doesn’t have integrity, then you want them to be dumb and lazy”

“Work for an organisation of people you admire, because it will turn you on. I always worry about people who say, ‘I’m going to do this for ten years; and if I really don’t like it very much, then I’ll do something else….’ That’s a little like saving up sex for your old age. Not a very good idea”

“Choosing your heroes is very important. Associate well, marry up and hope you find someone who doesn’t mind marrying down. It was a huge help to me”

Mr Buffett is wise and a very likeable chap.

Few people, however, are familiar with his business partner, Charlie Munger. And Charlie is my favourite of the pair.

Continue reading

2017 – Year in Review: A good vintage

At the end of each year, it is a useful practise to review the triumphs (and failures) of the past 12 months. It is an exercise of putting everything into perspective. 

2017 has been an incredible year for Parkinson’s research.

And while I appreciate that statements like that will not bring much comfort to those living with the condition, it is still important to consider and appreciate what has been achieved over the last 12 months.

In this post, we will try to provide a summary of the Parkinson’s-related research that has taken place in 2017 (Be warned: this is a VERY long post!)


The number of research reports and clinical trial studies per year since 1817

As everyone in the Parkinson’s community is aware, in 2017 we were observing the 200th anniversary of the first description of the condition by James Parkinson (1817). But what a lot of people fail to appreciate is how little research was actually done on the condition during the first 180 years of that period.

The graphs above highlight the number of Parkinson’s-related research reports published (top graph) and the number of clinical study reports published (bottom graph) during each of the last 200 years (according to the online research search engine Pubmed – as determined by searching for the term “Parkinson’s“).

PLEASE NOTE, however, that of the approximately 97,000 “Parkinson’s“-related research reports published during the last 200 years, just under 74,000 of them have been published in the last 20 years.

That means that 3/4 of all the published research on Parkinson’s has been conducted in just the last 2 decades.

And a huge chunk of that (almost 10% – 7321 publications) has been done in 2017 only.

So what happened in 2017? Continue reading

The EMPRSN talk #1

Recently I was invited to speak at the 6th Annual East Midlands Parkinson’s Research Support Network meeting at the Link Hotel, in Loughborough. The group is organised and run by the local Parkinson’s community and supported by Parkinson’s UK. It was a fantastic event and I was very grateful to the organisers for the invitation.

They kindly gave me two sessions (20 minutes each) which I divided into two talks: “Where we are now with Parkinson’s research?” and “Where we are going with Parkinson’s research?”. Since giving the talk, I have been asked by several attendees if I could make the slides available.

The slides from the first talk can be found by clicking here.

I have also made a video of the first talk with a commentary that I added afterwards. But be warned: my delivery of this second version of the talk is a bit dry. Apologies. It has none of my usual dynamic charm or energetic charisma. Who knew that talking into a dictaphone could leave one sounding so flat.

Anyways, here is the talk – enjoy!

I hope you find it interesting. When I have time I’ll post the second talk.

Prothena reports Phase 1b results for Parkinson’s immunotherapy

prothena_cmyk_fullcolor

This week the biotech company Prothena released the results of their phase 1b clinical trial for their treatment, PRX002 (also known as RG7935).

This is one of the first immuno-therapies being tested in Parkinson’s disease, and the results indicate that the treatment was active and well tolerated.

In this post we will review the press release and what it tells us regarding this clinical trial.


axs-studio-al-amyloidosis-mechanism-of-action-moa-animation-01

Antibodies binding to proteins. Source: AXS

When your body is infected by a foreign agent, it begins to produce some things called antibodies. In most cases, these are Y-shaped proteins that binds to the un-wanted invader and act as a beacon for the immune system. It is a very effective system, allowing us to go about our daily business without getting sick on a regular basis. Antibodies allow us to build up immunity, or resistance of an organism to infection or disease.

Scientist have harnessed the power of this natural process, and they have use it to develop methods of helping our bodies fight off disease.

The first approach is called Acquired Immunity (or adaptive immunity), and it is based on the idea that exposure of the immune system to a pathogen (disease/damage causing agent) creates an ‘immunological memory’ within our immune system, and this leads to an enhanced response to subsequent future encounters with that same pathogen.

Scientists have used the idea of acquired immunity to develop what we call vaccines – which are simply small, neutral fragments of specific pathogen that help the immune system to build up immunity (or resistance) before the body is attacked by the disease-causing pathogen itself.

getty_rf_photo_of_senior_man_getting_pneumonia_vaccination

Vaccination. Source: WebMD

The second approach is called Passive Immunity.

Passive immunisation is simply the sharing of antibodies. And that might sound a bit disturbing, but it is actually a naturally occurring process. For example, a mother’s antibodies are transferred to her baby in the womb via the placenta.

And again, scientists have devised ways of producing passive immunisation artificially. And recently researchers have been using this approach to attack many medical conditions (particularly cancer), in an area of medicine called immunotherapy.

Think of it as simply boosting the immune system by supplementing the supply of antibodies. Scientists can produce high levels of antibodies that specifically target a particular pathogen and then transfer those antibodies to affected people via an intravenous injection.

How is this being used for Parkinson’s disease?

Well, we have previously discussed the idea of a vaccine for Parkinson’s disease (click here to read that post), and we have been closely following the progress of an Austrian company, AffiRis, who are leading the vaccination approach (Click here for that post).

affiris_logo

Source: AffiRis

The vaccine approach is targeting the Parkinson’s disease associated protein, Alpha synuclein. It is believed that a bad kind of alpha synuclein is causing the spread of the condition, by being passed from cell to cell. The goal of the vaccine is to capture and remove all of the alpha synuclein being passed between cells and thus (hopefully) halt the progress of – or at least slow down – the disease.

And this week, another company – Prothena – has reported the results of their phase 1 trial for a passive immunity approach to Parkinson’s disease. They have been injecting subjects in the trial with a treatment called PRX002.

(Remember that a phase 1 trial simply tests the safety of a treatment in humans, it is not required to test efficacy of the treatment. Efficacy comes with phases 2 & 3 trials)

What is PRX002?

PRX002 is a monoclonal antibody. The scientists at the biotech company Prothena have artificially produced large amounts of antibodies to alpha synuclein and these have been injected into people with Parkinson’s disease.

cq5dam.web.1200.YTE_Chapter_31

Monoclonal antibodies. Source: Astrazeneca

Prothena provide a short video explaining this concept (click here to view the video).

So what were the results of the Prothena study?

The study was conducted in collaboration the pharmaceutical company Roche. It was a double-blind (so both the researchers and subjects did not know what they were receiving until the conclusion of the study), placebo-controlled study involving 80 people with Parkinson’s disease. The subjects were randomly assigned to one of six groups, which received either PRX002 or a placebo. There were six doses of PRX002 tested in the study (0.3, 1, 3, 10, 30 or 60 mg/kg).

The study was conducted over six-month, during which patients received three once-a-month injections of either PRX002 or placebo. The subjects were then followed for an observational period of three months.

According to the press release, no serious treatment-related adverse events were reported in PRX002 treated patients. Mild treatment-related adverse events (greater than anything experienced within the placebo group) were noted in 4 of the 12 subjects in the highest dosage group of PRX002, including constipation and diarrhoea.

Importantly, the investigators reported that thePRX002 antibodies were crossing the blood brain barrier and entering the brain. This resulted in a rapid reduction of alpha-synuclein levels (in some cases by up to 97 percent after a single dose!).

The follow-on Phase 2 clinical study is expected to begin in 2017.

What is the difference between the vaccine and the passive immunity approaches?

Basically, it comes down to levels of control. With a vaccination, once you have injected the vaccine and the immune system is activated, there isn’t much you can do to control the response of the body. And that immune memory is going to last a long time. The passive immunity response, on the other hand, requires regular injections of antibodies which can be stopped if adverse effects are noted.

Plus – and forgive me if I sound a little bit cynical here – drug companies prefer a regular treatment approach (which they can charge for each visit) compared to a one-shot cure. It’s simply a better business model.

What happens next?

In both cases – the vaccine and the passive immunity approaches – phase 2 trials are being set up by the respective companies and we will wait to see have affective these treatments are at slowing down Parkinson’s disease.

If they are affective, expect big headlines in the media and plans for adults everywhere to start being vaccinated. If they fail,…. well, we will have to re-address our understanding of the role of alpha synuclein in Parkinson’s disease.

Interesting times lie ahead.


The banner for todays post was sourced from Prothena

Vaccine for Parkinson’s – AFFiRiS update

 

affiris_logo

Interest press release from the biotech company AFFiRiS last week (Click here for the press release) regarding their clinical trial of a vaccine for Parkinson’s disease. We have previously outlined the idea behind the trial (Click here for that post) and the team at Michael J Fox foundation also provide a great overview (Click here for that – MJF are partly funding the trial). In today’s post we will briefly review what results AFFiRiS has shared.


getty_rf_photo_of_senior_man_getting_pneumonia_vaccination

Vaccination. Source: WebMD

Vaccination represents an efficient way of boosting the immune system in the targeting of foreign or problematic agents in the body. For a long time it has been believed that the protein Alpha Synuclein is the ‘problematic agent’ involved in the spread of Parkinson’s disease inside the brain. Alpha synuclein is required inside brain cells for various normal functions. In Parkinson’s disease, however, this protein aggregates for some reason and forms circular clusters inside cells called Lewy bodies.

Fig2_v1c

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

It has been hypothesized (and there is a lot of experimental evidence available to support the idea) that released alpha synuclein – freely floating between brain cells  – may be one method by which Parkinson’s disease spread through the brain. With this in mind, groups of scientists (like those at AFFiRiS) are attempting to halt the spread of the condition, by training the immune system to target free-floating alpha synuclein. Vaccination is one method by which this is being attempted.

AFFiRiS is a small biotech company in Vienna (Austria) that has an ongoing clinical trial program for a vaccine (called ‘AFFITOPE® PD01A’) against alpha synuclein. The subjects in the study (22 people with Parkinson’s disease) received four vaccinations – each injection given four-weeks apart – and then the subjects were observed for 2-3 years (6 additional subjects were included in the study for comparative sake, but they did not receive the vaccine.

 Last week the company issued a press release regarding a phase 1 trial (AFF008), which indicated that PD01A is safe and well tolerated, and causing an immune response (which is a good thing) in 19 of 22 (86%) of vaccinated subjects. In 12 of those 19 (63%) participants with and immune response, the researchers found alpha-synuclein antibodies in the blood, suggesting that the body was reacting to the injected vaccine and producing antibodies against alpha synuclein (for more on what antibodies are, click here).

The scientists also conducted some exploratory efficacy assessments – to determine if they could see if the vaccine was working clinically and slowing down the disease. Eight of the 19 (42%) subjects with an immune response, had no increase of their dopaminergic medication (eg. L-Dopa) over the course of the observational period (average three years per subject). And five of those eight subjects had stable clinical motor scores at the end of the study.

The company also conducted parallel laboratory-based experiments which indicate that AFFITOPE® PD01A-induced antibodies are binding to alpha-synuclein in various models of Parkinson’s disease.

The company will be presenting the results on a poster at the 4th World Parkinson Congress in Portland, Oregon, USA on September 21.

So this is a good result right?

It is easy to get excited by the results announced in the press release, but they must be taken with a grain of salt. This is a Phase I trial which is only designed to test the safety of a new therapeutic agent in humans. From this point of view: Yes, the study produced a good result – the vaccine was well tolerated by the trial subjects.

Drawing any other conclusions, however, is not really possible – the study was not double-blind and the assignment of subjects to the treatment groups was not randomize. In addition, the small sample size makes it very difficult to make any definitive conclusions. It must be noted that of the 22 people with Parkinson’s disease that started the study, only five exhibited stabilized clinical motor scores at the end of the study. It may be too soon to tell if the vaccine is having an effect in most of the people involved in the study. Thus longer observation periods are required – which the company is currently undertaking with their follow-up study, AFF008AA. The results of that study are expected in middle-late 2017.

We shall keep you posted.


The banner for today’s post was sourced from AFFiRiS