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?
The short answer to the question is to list the top 10 Parkinson’s research events – according to yours truly – of 2017. And they are:
1. We discovered that drugs can be re-purposed for Parkinson’s
The results of the Phase II clinical trial of Byduren (Exenatide) in Parkinson’s suggested that this diabetes drug can have an impact on the motor features of the condition (Click here, here, here and here to read more about the study results). 2017 gave us proof-of-principle for re-purposing clinically available drugs. And the really exciting aspect of that event is that there is a large number of the ongoing clinical trials for Parkinson of other clinically available drugs (think Ambroxol, Nilotinib, Simvastatin, Deferiprone, etc), and we will be seeing results for some of trials in 2018.
2. We learned a lot more about the genetic risk factors of Parkinson’s
We discovered new genetic variants that are associated with an increased risk of Parkinson’s, and some researchers now believe that 30% of cases of Parkinson’s may have an inherited component to them (Click here and here to read more about this – there is a SoPD post coming on this topic). In one 2017 study alone, we learned of 17 new genetic anomalies associated with Parkinson’s. These findings are really important, not only from a diagnostic/subtyping point of view, but also because they are instrumental in pointing researchers towards the underlying biology that is involved in the development of this condition. And we are expecting more from this area of research in 2018.
3. We learned that the asthma drug Salbutamol may be having an impact on Parkinson’s
Researchers at Harvard University and in Norway found that the Beta2-Adrenoreceptor agonist (or activator), Salbutamol (which is commonly used for the treatment of conditions of the lungs such as Asthma – a common long-term inflammatory condition of the lungs) was associated with decreased risk of developing Parkinson’s disease – literally a 1/3 reduction in risk.
The researchers also reported that the drug, Propranolol which blocks the Beta2-Adrenergic receptor was associated with a two-fold increase in the risk of developing Parkinson’s disease (see graph below):
The researchers found that Beta2-Adrenoreceptor agonists (like Salbutamol) may be having this effect by reducing the production of the Parkinson’s associated protein Alpha Synuclein. This class of drugs is now being further researched and we can hopefully expect more data in 2018 (Click here to read the research report and click here to read a SoPD post on the topic).
4. Non-invasive gene therapy suddenly appeared on everyone’s radar
Future therapies for Parkinson’s may make use of carefully engineered viruses that can be injected into your arm and then travel to your brain where they will only infect specific cells in order to correct vulnerabilities to Parkinson’s.
In 2017, we moved from characterising this new technology, to correcting mouse models of Parkinson’s using this approach, to testing it in primates (but these final results suggest we still have some way to go – Click here for more on this new technology). I know of numerous Parkinson’s research groups who are now playing with this new technology and we can expect to see major strides in this area in 2018.
5. We found out that use of the PPARgamma agonist Glitazone is associated with a reduced incidence of Parkinson’s
This drug which is used for treating diabetes was reported (by two independent research reports) to be associated with a 28% reduced risk of developing Parkinson’s (Click here and here to read the research reports).
Previous clinical research, however, indicates that PPARgamma agonists may not slow the progression of Parkinson’s (Click here to read the research report from a Phase II clinical trial of Pioglitazone in early Parkinson’s), but a better understanding of how this class of drugs is reducing the risk of Parkinson’s may provide useful insights into the development of the condition.
6. Gene editing technology began to show its true potential in Parkinson’s research
Gene editing technology (such as CRISPR-Cas9 – Click here to read more about how this technology works) is now being widely used in Parkinson’s research. Large screening studies are highlighting new biological pathways and novel drug targets for Parkinson’s (Click here to read about that).
We will definitely see more – a lot more – of this sort of research in 2018. Critically these tools will help to speed up the process of researching the underlying biology of Parkinson’s. It is extremely powerful stuff, and in 2017 everyone started using it.
7. The rise of patient advocacy and involvement really came to the fore
From Parkinson’s UK initiating new virtual biotech companies (Click here to learn more about this) to focused online communities discussing the current Parkinson’s research (such as this really great Facebook group), 2017 has seen even greater involvement in the research being conducted on Parkinson’s from the community that is affected by the condition.
And this greater participation is having major benefits as we have seen in the example of the lady who can smell Parkinson’s which has led from one woman bravely admitting a unique ability to entirely new branches of research. Individuals within the community stepping forward and providing the initial idea for a project or resource have been a serious driving force this year. I have a funny feeling that this will pay big dividends in 2018.
8. Numerous new clinical trials targeting different aspects of Parkinson’s began
From the initiation of the long awaited Phase II clinical trials for the cancer drug Nilotinib (Click here to read a SoPD post on this trial) to the Phase I testing of completely novel compounds, 2017 saw a great deal of clinical research commence for new drugs focused on different aspects of Parkinson’s.
9. Parkinson’s research went to places it’s never been before… like space
In 2017, we saw bold new Parkinson’s-related research projects commence, including one which involved sending a Parkinson’s associated protein (called LRRK2) into space to grow better crystals in a low gravity environment in order to better understand the structure of the protein.
A more complete understanding of the structure will allow for better drugs to be designed that specifically target certain regions of this protein. 2018 will hopefully provide the research community with a lot of new and interesting research findings as a result of this and other impressive studies.
10. First indications of non-drug therapies impacting the progression of Parkinson’s
Late in 2017, a resaerch report of a Phase II randomised clinical trial of 128 people with recently diagnosed Parkinson’s (from ‘Study in Parkinson’s disease of Exercise’ (SPARX) project) found that high-intensity (but not moderate) treadmill exercise may impact disease progression (Click here here to read the research report)
This kind of research provides proof-of-principle that other forms of non-drug related treatments could also be having an impact. It would be interesting to see further developments in this area in 2018.
These were my big ten events for Parkinson’s research in 2017.
Yes, they leave out a lot (such as all the new and exciting drug targets, not to mention all of the new high-tech self tracking gadgets and tools). But I thought that these ten were the main events/themes of the last 12 months.
Please feel free to contact me or to leave a comment in the comments section below if you think I am wrong about any of them, or if you feel I have missed out something important.
I am happy to be corrected.
EDITOR’S NOTE #1: The information provided by the SoPD website is for information and educational purposes only. Under no circumstances should it ever be considered medical or actionable advice. It is provided by research scientists, not medical practitioners. Any actions taken – based on what has been read on the website – are the sole responsibility of the reader. Any actions being contemplated by readers should firstly be discussed with a qualified healthcare professional who is aware of your medical history. While some of the information discussed in this post may cause concern, please speak with your medical physician before attempting any change in an existing treatment regime.
OK, so that was the short answer. Now for…
The ridiculously longer answer regarding what happened in 2017:
While I fear that the rest of this answer will read a lot like a long and never-ending shopping list, we are going to persevere with it anyway. I think it is important for people to truly appreciate how much is happening (and how quickly it is all happening).
Events will be provided in chronological order, and I have tried to mix things up a little bit – offering snippets of world news in amongst the research findings – to try and keep it entertaining. It is still a very long read, however, and you will be forgiven for giving up half way down.
I just hope that you find something of interest before you reach that point.
Fake news? Source: CNN
As protest marches around the world welcomed President Donald Trump and a new era in global politics, the Parkinson’s research community were gearing up for a big year. The results of some important clinical trials were being prepared for release and new research findings were being submitted for publication.
The news kicked off with a clinical trial update:
The gene therapy company Voyager Therapeutics provided an update on their ongoing clinical trials for Parkinson’s. The treatment involves injecting engineered viruses into the brain of people with Parkinson’s, and the infected cells will help to produce more dopamine. Thus far the updates from the trial have been very encouraging (Click here to read more about this).
Next, researchers at Harvard University and University of Cambridge identified a substance derived from the dogfish shark that demonstrates amazing ability to reduce the clustering of Parkinson’s associated protein alpha synuclein.
The compound – called Squalamine – demonstrates a wide range of antimicrobial activity, but also blocks the clustering of toxic forms of alpha synuclein. The researchers were very keen to advance this research towards clinical testing (Click here to read more about this), and as we shall see below, just a few months after this research was announced a clinical trial in Parkinson’s was initiated for a drug very similar to this compound (see below).
Following that research report, scientists at the MRC Toxicology Unit in Leicester (UK) found that a diet high in the niacin may be very beneficial for people with Parkinson’s-associated PINK1 genetic mutations. Experimenting on fruit flies, the researchers found that a niacin-rich diet could rescue the mitochondrial problems in the flies, and also protect neurons from degeneration – Click here to read more about this or watch this video:
And just as the month was finishing, researchers at Johns Hopkins University School of Medicine (in Baltimore) announced very interesting results dealing with a protein called PARIS. Accumulation of PARIS protein is dangerous for cells as it can cause cell death if levels get too high. Usually, levels of PARIS are controlled by the Parkinson’s-associated protein PINK1, but in people with PINK1 genetic mutations, this process is dysfunctional and can make cells more vulnerable as PARIS piles up (Click here to read more about this).
The pathway of Paris. Source: Cell
We are currently awaiting follow up research on this PARIS-related result. It would be interesting to see if inhibitors of PARIS exist, and if they can slow down Parkinson’s in people with PINK1 genetic mutations. Hopefully we will find out in 2018 whether such inhibitors exist.
Oh, and we also were given a new theory of Parkinson’s disease – Click here to read about that.
And all of that happened in just the first month of the year!
Let’s move on to:
Remember all the world news stuff that happened in February?
- North Korea prompted international condemnation by test firing a ballistic missile across the Sea of Japan.
- Discovery of seven Earth-sized planets orbiting the star Trappist-1 – raises possibility of extraterrestrial life.
- British MPs vote in favour of the European Union Bill, allowing the government to begin Brexit.
- Executive Order 13769 came into effect… and then,… well, out of effect.
- And lest we forget the discovery of a new (mostly underwater) continent Zealandia in the South Pacific announced.
New global superpower: Zealandia (Pink outline). Source: Wikipedia
Meanwhile in research labs around the world, investigators were reading about the bacteria in our gut and what differences exist between healthy individuals and those with Parkinson’s (Click here to read more about this). Scientists were also learning that blocking a protein called activating transcription factor 4 (or Atf4) could reduce cell death that is observed in a fly model of Parkinson’s (Click here to read more about that research). And they were reading about research from New Zealand highlighting ‘tunnelling nanotubes‘ as a possible method by which toxic forms of alpha synuclein protein may being passed between cells
A tunnelling nanotube between two cells. Source: Pasteur
In February, the Parkinson’s research world read about amazing research suggesting that low doses of the antibiotic doxycycline could be used to treat synucleinopathies (like Parkinson’s), as the drug demonstrated the ability to remodel alpha synuclein from a toxic version towards a non-toxic form (Click here to read the research report and click here to read a SoPD post on the topic).
February also saw the initiation by Martin Taylor in Scotland of the Parkinson’s research interest group on Facebook. It is a very good source of information regarding the most up to date research on Parkinson’s.
We also learned of positive Phase III clinical trial results for the inhalable L-dopa treatment, called CVT-301 (now known as Inbrija), which demonstrated a statistically significant improvement in motor function in people with Parkinson’s who experience issues during OFF periods (Click here to read more about this news, and click here to read more about inhalable L-dopa).
The ARCUS inhalation technology. Source: ParkinsonsLife
This was possibly the highlight of the year for the biotech company – Acorda Therapeutics Ltd – behind the product because, as we shall see below, the rest of the year was rather rough for them.
In February, we also found out about a clinical trial in South Korea that was just starting which is looking at slowing down the cell loss associated with Parkinson’s.
Kainos Medicine‘s new experimental treatment, called KM-819, is an inhibitor of a protein called Fas Associated Factor 1 – this is a protein directly involved with cell death. By inhibiting the function of this protein, Kainos is hoping to slow the progression of Parkinson’s (Click here to learn more). They should have just completed the phase I ‘safety’ trial of KM-819, and we should know the results of that trial in 2018.
February also saw great excitement (and a sense of relief) from the Parkinson’s community with the initiation of a Phase II clinical trial for the cancer drug Nilotinib in people with Parkinson’s.
After Nilotinib demonstrated some very impressive Phase I results in late 2015 (Click here to read more about that), the research team at Georgetown University started recruiting participants for their phase II double-blind, randomised efficacy study (Click here to read more about this – and Click here to read the press release). Results from this study are expected mid 2020.
February also saw the initiation of a new clinical trial by the biotech company Sanofi Genzyme, which was seeking to evaluate their drug GZ/SAR402671 (also known as Ibiglustat) in GBA-associated Parkinson’s.
GBA is one of the most common genetic risk factors associated with Parkinson’s, and it results in a reduction in the production of a particular enzyme involved in the waste disposal system of cells (Click here to learn more about GBA). The MOVES-PD clinical trial (Click here to read more about the trial) is a phase II clinical study that will be involve in two parts:
- A dose escalation study to determine safety in early-stage GBA-associated Parkinson’s.
- A randomised, double blind study of efficacy of GZ/SAR402671, as compared to placebo in early-stage GBA-associated Parkinson’s
GZ/SAR402671 is a glucosylceramide synthase inhibitor, which would block the production of the proteins that GBA helps to break down thus reducing the work required for this enzyme. Preclinical results look very promising (Click here to read some of the research on this). The MOVES-PD trial will finish in 2022 (Click here for the press release).
Yet another busy month!
Moving on to:
In March 2017, the world bid farewell to rock n’ roll music legend Chuck Berry.
Legend. Source: NYTimes
The United Kingdom triggers article 50 of the Lisbon Treaty – officially starting the BREXIT negotiations, and SpaceX conducted the world’s first re-flight of an orbital class rocket:
In Parkinson’s-related news, the FDA approved the use of Xadago® (safinamide) for the treatment of Parkinson’s as add-on therapy to levodopa/carbidopa, on March 21, 2017 (Click here for the press release).
Researchers demonstrated that a cancer treatment called Leucovorin (folinic acid) can reduce cell loss associated with a PINK1-associated parkinson’s model (in flies) – Click here to read that research report.
And there was also a publication indicating that having viral hepatitis increases one’s risk of developing Parkinson’s disease (Click here to read that research report and Click here to see the SoPD post about the research).
We also learned about a novel potential therapy being developed by Greek researchers, called BRF110, which is a Nurr1:RXR-selective activator. Nurr1 is a protein that is critical to the development and survival of dopamine neurons, and thus researchers believe that drugs like BRF110 which activate Nurr1 could be very useful in slowing down Parkinson’s. The initial pre-clinical research looks very encouraging (Click here to read the SoPD post on this and other Nurr1-based research).
Nurr1 binding to DNA. Source: Wikipedia
In March, researchers published data on a genetic risk factor for Parkinson’s called ATP13A2 (also called PARK9). Until this study was made available, very little is known about the physiological role of ATP13A2 in stressed cells, and the results of the study could lead to novel therapeutic targets (Click here to see that study).
We also had research published that indicating that adaptive deep brain stimulation may be better at treating Parkinson’s than the standard approaches to deep brain stimulation (Click here to read that research).
And Australian researchers identified Nix1 as a potential drug target for people with PINK1 or PARKIN-associated Parkinson’s (Click here to read that research and click here to read an SoPD post on the topic).
On the the 7th March, the University of Sheffield and Parkinson’s UK launched a new £1 million virtual biotech company. The company is called Keapstone Therapeutics and it is first venture of its kind. The company is focused on identifying compounds involved in activating biological pathways (the KEAP1-Nrf2 pathway) that reduce free radicals and oxidative stress (Click here to read a SoPD post about this venture).
Another biotech company, Inhibikase Therapeutic, won a large Michael J Fox Foundation Grant to study c-Abl inhibitors (drugs that are similar to the cancer drug Nilotinib – click here to read the press release).
In the clinic in March, a randomised, double-blind, placebo-controlled clinical trial indicated that co-supplementation of omega-3 fatty acids and vitamin E led to improvements in motor features (as determined by UPDRS) and some metabolic profiles (Click here to see that research report).
The biotech company NeuroDerm announced that a Phase II trial of continuous delivered of L-Dopa/carbidopa in advanced Parkinson’s achieved its primary endpoint, with a significant reduction in dyskinesias and a complete reduction of OFF-time to zero hours in 66% of responders (Click here to read the press release).
Not bad for one month (and there was a whole lot more than just this!).
On the 1st April, singer Bob Dylan finally received his Nobel Prize for Literature at a private ceremony in Stockholm. Six days later (7th April), US President Donald Trump ordered missile strike on a Syrian airfield after a chemical weapons attack on Khan Sheikhoun. And on the 18th April, Theresa May announced a snap general election for the 8th June.
In the world of science, the March for Science – a series of rallies and marches held in more than 600 cities across the world – were held on Earth Day (April 22, 2017). The goal of the activities was to emphasise that science represents a common good and to call for evidence-based policy in the public affairs.
For the Parkinson’s community, the month of April had important significance: Parkinson’s Awareness Week was held between April 10-16th and it was a big deal this year given the 200 year anniversary.
There was a great deal of activity during Parkinson’s Awareness Week, with a lot of social media being used to further bring the public’s attention to this condition:
As far as the Parkinson’s research went, we learned that daily administration of the clinically available drug Ambroxol results in increased levels of glucocerebrosidase activity in the brains of primates. Glucocerebrosidase is the enzyme that is reduced in people with GBA genetic mutations, and Ambroxol is currently being tested in clinical trials for Parkinson’s. This result was very reassuring for the hypothesis underlying the clinical trials (Click here to read the research report and click here for a SoPD post on the topic).
New research results suggested no association between appendectomy and the development of Parkinson’s (Click here to read the research). This new finding is in contrast with previous research on appendectomies (Click here to read a SoPD post on this topic).
In April, researchers also found that Sodium butyrate rescues dopamine-producing cells from alpha synuclein-induced issues (Click here to read more about this research). This compound is found in a normal diet, it is produced in large amounts from dietary fiber in the gut and it is present in Parmesan cheese and butter. The most common source of sodium butyrate in the gut, however, is from consumption of legumes.
From a screen of many compounds, researchers also identified a steroid called Hydrocortisone (or cortisol) as an activator of Parkinson’s related gene PARKIN. This interaction causes more PARKIN protein to be produced, which was found to rescue a rodent model of Parkinson’s. And the dose of Hydrocortisone required, was below the normal clinically used levels that can caused cellular toxicity (Click here to read the research report and click here to read a SoPD post on the topic).
Prana Biotechnology presented interesting preclinical results of their candidate drugs, PBT434 (an iron reducing drug), in both cell culture and animal models of Parkinson’s (Click here to read the research report on this work which was published in July, and Click here to read a SoPD post on the topic).
Herantis Pharma initiated a Phase 1-2 clinical study of Cerebral Dopamine Neurotrophic Factor (CDNF) in Parkinson’s – CDNF is very similar to GDNF in that they are both neurotrophic factors (chemicals that nurture neurons), and Herantis will be pumping CDNF into the brains of people with Parkinson’s (Click here to read the press release).
Prothena Corp presented an update of their immunotherapy product PRX002 currently in clinical trials for Parkinson’s. This drug is an antibody which will help the immune system to target the toxic form of the Parkinson’s associated protein alpha synuclein and remove it from the body (Click here to read the press release and click here to read a SoPD post on the topic of immunotherapy)
Pharma Two B Ltd published positive results from a randomised clinical trial of their Rasagiline & Pramipexole combination product called P2B001 in early Parkinson’s (Click here to see the research report).
Research from a small phase II study conducted by the biotech company Avanir Pharmaceuticals indicated that their clinically available product Nuedexta (sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator – dextromethorphan plus quinidine) may be useful in treating L-dopa-induced dyskinesias (Click here to read more about the clinical trial and click here to see the results of the study).
And finally there was VERY interesting results from a Phase I open-label clinical trial of a clinically available drug called Sargramostim in Parkinson’s. This drug is an immunomodulator and this study represented a novel approach to slowing down Parkinson’s, by reducing the immune system’s ability to remove sick or dying cells (Click here to read the research report and click here to read a SoPD post about the topic).
The researchers behind the study (image above) are now attempting to determine a better formulation of the drug to take forward for further evaluation in Parkinson’s.
Another busy month!
In May, as Emmanuel Macron won France’s presidential election (May 7th) and US President Donald Trump fired FBI Director James Comey (May 9th), the Parkinson’s community lost one of its generals.
Tom Isaacs, co-founder and president of The Cure Parkinson’s Trust, passed away unexpectedly on 31st May.
In 1996 – at just 27-years of age – Tom, a London-based surveyor, was diagnosed with Parkinson’s. After dealing with the initial shock of it all, Tom embraced his situation and became a committed, tireless activist. He firstly walked the entire coastline of the UK to raise money and awareness for the condition.
His book, “Shake well before use“, discusses that trip and adapting to life with Parkinson’s. It is a fantastic read. Upon returning from his epic walk, he (along with three others) founded and set up the Cure Parkinson’s Trust. It is pretty safe to say that other than Michael J Fox, Tom has had the most impact on marshalling scientific research efforts to find a cure for Parkinson’s. And he did it all with energy and humour.
The tributes were many, and some provide a wonderful insight into who Tom was:
His absence is a terrible loss, but he certainly pointed us in the right direction and has left an incredible legacy.
In May, the Parkinson’s research community found out that deeper sleepers have a slower progression of the condition (Click here to read more about this); early-onset mild cognitive impairment in Parkinson’s appears to involved altered cholinergic activity (Click here to read the research report); and levels of Parkinson’s-associated protein alpha synuclein can be reduced without impairing mitochondrial function (Click here to read that research report).
Researchers found that genetic mutations in Base excision repair genes, APEX1 and OGG1 (which are responsible for repairing oxidative DNA damage in cells) in addition to exposure to pesticides increases one’s risk of developing Parkinson’s (Click here to see this research report). We also read a research report that indicated a protein, called SOD1, which is involved with Motor neuron disease, may also be involved with the cell loss associated with Parkinson’s (Click here to read an SoPD post about this research).
In the clinic, a double blind clinical study of iron chelator Deferiprone in Parkinson’s exhibited mild results (a trend for improvement in motor-UPDRS scores, though not significant) after 6 months of treatment. These results suggested to the researchers that further/longer investigations were justified (Click here to read the research report).
We also learnt that the much anticipated clinical trial of GDNF in Bristol had failed to meet its primary endpoint. The initial analysis suggested that the treatment was safe but there was no clear difference between those who received GDNF and those who received the placebo after 9 months. We are now awaiting the full analysis of all the data to get a more comprehensive picture of the effects of this neurotrophic factor on Parkinson’s (Click here to read a SoPD post about the initial results).
In more positive news, Enterin Inc. enrolled their first subject in their RASMET study which is evaluating the synthetic version of squalamine in Parkinson’s. Squalamine is the compound that was derived from the dog fish shark that I mentioned in the January. As far as going from the lab to the clinical trial, that’s pretty quick! The compound does not appear to be able to cross the blood brain barrier, however, and this trial is solely focused on dealing with Parkinson’s associated constitpation (Click here for the press release and click here to read more about the clinical trial).
Five months down, a lot of research done. Moving on:
While US President Donald Trump was announcing the withdrawal of the USA from the Paris Climate Agreement (June 2nd) and the British General Election resulted in a hung parliament denying Prime Minster Theresa May and the Conservative party of the majority they desired (June 9th), the Parkinson’s research community was gearing up for a flood of Parkinson’s-related results being presented at the Movement disorder meeting in Vancouver (Canada).
And it was a very big month for Parkinson’s research:
- A huge genetic sequencing study of almost 140,000 individuals found common genetic pathways between Parkinson’s and several autoimmune conditions, including diabetes, Crohn disease, and multiple sclerosis (Click here to read this research report)
- Researchers also published data suggesting that seasonal flu vaccines may help reduce the likelihood of developing Parkinson’s (Click here to read the research report and click here to read a SoPD post on the topic)
- Data was published that suggested that the Parkinson’s-associated protein alpha synuclein may actually protect melanoma cells from autophagic cell death (Click here to see this research report).
- Tangeretin, a protein in citrus peels, was found to inhibit neurodegeneration in models of Parkinson’s (Click here for this study)
- Researchers in London found that higher body mass index (BMI) leads to lower risk of developing Parkinson’s (Click here to read more about this and click here to read a SoPD post on the topic)
- The risk of developing Parkinson’s in people with diabetes might be limited to those with longer disease duration (Click here to find out more about this).
In one of the major research stories of the month, we learnt that immune cells (T-cells) collected from the blood of people with Parkinson’s recognise particular components of alpha synuclein, suggesting that this Parkinson’s-associated protein could be causing an immune response (Click here to read more about this, Click here to read a SoPD post on this research, or click here for the Parkinson’s UK blog report on the topic).
In another really interesting story, non-invasive deep brain stimulation became a possibility in June, with the publication of proof-of-principle experiments, demonstrating that enveloping temporal interference stimulation could stimulate neurons deep inside the brain AND could be targeted (Click here to read the research report and click here to read a SoPD post on the topic).
In clinical research, we heard for the first time about spinal cord stimulation research for Parkinson’s, which was been presented at the Movement Disorder meeting. This technique is used to alleviate severe back pain, but has been applied to Parkinson’s disease to try and help with gait related issues (Click here to read a SoPD post on this topic). We are currently awaiting the publication of the research presented at the MDS meeting, but several groups are working on this approach:
More importantly, Austrian biotech company AFFiRiS announced that their product PD03A – which is an alpha synuclein vaccine – met the primary endpoint of their Phase I study for Parkinson’s.
The vaccine for Parkinson’s was well tolerated induced an immune response. Very positive stuff – now we wait to see if the immunotherapy treatment actually has an impact of disease progression (Click here to read the press release).
In other clinical research news, Adamas Pharmaceuticals Phase III EASE LID study of Amantadine demonstrated efficacy in reducing L-dopa-induced dyskinesia in Parkinson’s (Click here to read the research report). Merz Neurosciences announced positive Phase III results of their drug Xeomin for hypersalivation in Parkinson’s (Click here to read the press release). And Adenosine 2A receptor antagonist Preladenant failed as a monotherapy for early Parkinson’s in a Phase III clinical trial (Click here to read more about this and click here to find out more about the clinical trial).
In dramatic world news White House Press Secretary Sean Spicer resigned as acting White House Communications Director on the 21st July. He was replaced by Anthony Scaramucci.
In other dramatic world news Anthony Scaramucci was removed as White House Communications Director after less than two weeks on the job (July 31st).
(Big yawn – long post huh? I wonder if anyone is still actually reading this gibberish?)
What else happened in July?
Tesla Motors produces its first mass-market car, the Model 3 (7th July), the British Lions tie 15-15 with New Zealand All Blacks in their 3rd rugby match to tie the series (July 8th – on the whole I thought it was a good series), and NASA’s Juno spacecraft made it closest ever pass over Jupiter’s Great Red Spot – at 9,000 kilometres overhead (July 10th).
In the Parkinson’s research world, scientists learned that:
- Alterations in the visual system can be detected in early stages of Parkinson (Click here to read more on this)
- Excessive alpha synuclein changes the trafficking & signalling of neurotrophic factor BDNF in mouse model of Parkinson’s (Click here to read the research report)
- Alpha synuclein control of mitochondria in human-derived neurons is disrupted by Parkinson’s associated mutations (Click here to read the research report)
- The Parkinson’s associated LRRK2 G2385R genetic variant is a partial loss-of-function mutation that affects synaptic vesicle trafficking through altered protein interactions (Click here to read the research report)
- The antidepressant Nortriptyline inhibits Parkinson’s associated aggregation of alpha synuclein in cell and animal models (Click here to read more about the research report, and click here to read a SoPD post on this topic)
- Midnolin is a novel regulator of Parkinson’s associated PARKIN protein levels and is itself associated with Parkinson’s (Click here to read the research report)
One of the most interesting studies this month was a report that used mouse models, patient-derived neurons, & postmortem brain tissue to demonstrate a possible connection between Parkinson’s associated LRRK2 protein activity and the internal domain of the Amyloid precursor protein (circled in the image above), which is usually associated with Alzheimer’s (Click here to read the research report, and click here to read a SoPD post on the topic).
A double-blind, randomised, controlled, crossover study Mucuna pruriens in Parkinson’s. Mucuna Pruriens are one of the best natural sources of L-dopa, and in this study found that the clinical effects of high-dose Mucuna Pruriens were similar to L-dopa alone at the same dose, but with a more favourable tolerability profile (Click here to read the research report, and click here to read a SoPD post on this topic).
Prexton Therapeutics announced start of a Phase II trial of PXT002331 (Foliglurax) for Parkinson’s with L-dopa induced dyskinesias (Click here to read the press release). Foliglurax is a positive allosteric modulator of the metabotropic glutamate receptor 4 (mGluR4) – Click here to read a SoPD post on this topic.
A very busy summer. And things were only just warming up for Parkinson’s research.
On the same day in August there was both a total solar eclipse visible across North America, and London’s parliament clock tower bell – affectionately named ‘Big Ben’ – chimed for the last time before a four-year restoration started (August 21st). Hurricane Harvey made landfall in Texas, and wreaked havoc (August 25th).
In August, Kenya also brought in the world’s toughest ban on single use plastic bags with the possibility of a US$38,000 fine and a four year jail sentence (August 28th). And lest we forget, the late author Terry Pratchett’s unfinished works were destroyed by steamroller as per his instructions (August 30th).
Seriously Terry. Why?
August started with a “BANG” for the Parkinson’s community with the release of the Byduren (Exenatide) phase II clinical trial results on the 3rd August (Click here to read the research report, and Click here and here to read SoPD posts about the results). As I indicated in the short version to this answer above, this was a watershed moment for Parkinson’s research – confirmation that a clinically available drug can be re-purposed for this condition. And while the positive effects were limited to just the motor features of Parkinson’s, it still represented the moment that the mind set moved from “If we find a cure” to “When we find a cure”.
In other research news, we learned that:
- The wonder compound EGCG can protect cells against alpha synuclein build up in models of Parkinson’s (Click here to read this research report, and click here for a SoPD post on this topic)
- A protein called Mitochondrial Division Inhibitor-1 (mdivi-1) reduces mitochondrial dysfunction in model of Parkinson’s (Click here to read this research report, and click here for a SoPD post on this topic)
- The anti-helminth drug, Nitazoxanide, could be proposed for Parkinson’s as it demonstrates neuroprotection in models of Parkinson’s (Click here to read the research report)
- Controlling one’s RAGE is important: Inhibition of Receptor for Advanced Glycation Endproducts (RAGE) using multimodal blocker FPS-ZM in models of Parkinson’s reduced dopamine cell loss (Click here to read the research report)
- Smartphone accelerometer recordings of tremor can distinguished between healthy control subjects and people with Parkinson’s (& essential tremor) (Click here to read the research report)
One of the coolest Parkinson’s research events of the month, however, occurred on the 14th August when a rocket lifted off from Florida. It was taking a Parkinson’s-related research project to the international space station in orbit.
Sunrise on the ISS. Source: Wikipedia
The experiment (called ‘Crystallization of LRRK2 Under Microgravity Conditions‘ or CASIS PCG 7) will involve growing crystals of the Parkinson’s associated protein LRRK2. The project is being funded by the Michael J Fox foundation and it will hopefully provide us with a better understanding of the structure of LRRK2 in order to design better drugs targeting this protein (Click here to read a SoPD post on this topic).
In the clinic, Parkinson’s researchers started spelling out very personalised approaches to managing Parkinson’s in the modern era (Click here for a very good commentary on this), and the FDA approved GOCOVRI (previously called ADS-5102) – an extended-release version of Amantadine – for the treatment of dyskinesias in Parkinson’s (Click here to read the press release).
Oh, and the pharmaceutical company AstraZeneca announced that they had agreed a commercial tie-up with Japanese drugs company Takeda to develop their antibody therapy MEDI1341 (which has been tested in healthy individuals in phase I clinical studies) for degenerative neurological conditions including Parkinson’s (Click here to read more about this).
It is fair to say that August was a HUGE month for Parkinson’s research.
Major world events in the month of September:
- Cassini–Huygens ends its 13-year mission by plunging into Saturn, becoming the first spacecraft to enter the planet’s atmosphere.
- The International Olympic Committee awards Paris and Los Angeles the right to host the 2024 and 2028 Summer Olympics
- A massive 7.1 force earthquake strikes central Mexico
- The studio track version of Big Shaq’s “Man’s not hot” was released (“Two plus two is four, Minus one that’s three, quick maths…” – please don’t ask me what it all means)
What else happened?
- The Caribbean and United States were struck by Hurricane Irma, a Category 5 hurricane that was the strongest hurricane ever recorded in the Atlantic basin
Angry Irma. Source: Wikipedia
In the realm of Parkinson’s, we found out that use of the PPAR agonist Glitazone (a drug used for treating diabetes) is associated with a 28% reduced risk of developing Parkinson’s (Click here and here to read the research reports).
During the month of September, Parkinson’s researchers:
- Reported about the curious effects that seasons can have on Parkinson’s – for example, treatment doses are 4.2% greater in January and 4.5% lower in July (in the northern hemisphere – Click here to read more)
- Determined that we can use medical claims data to identify people with Parkinson’s prior to diagnosis -using just demographic data and selected diagnosis/procedure codes which are readily available in administrative claims data, it is possible to identify individuals with a high probability of eventually being diagnosed with Parkinson’s (Click here to read more on this)
- Found that metal levels are altered in the olfactory regions of of the brain in people with Parkinson’s – Kiwi researchers found that zinc was high in the olfactory regions and it was also detected in Lewy bodies and mitochondria. They also suggested that increased iron and sodium levels may relate to the loss of olfactory function (Click here to read the research report)
- Reported that an increase of reproductive life span delays age of onset of Parkinson’s in females by 30 months – basically, the more babies women have, the later the onset of Parkinson’s (Click here to read the research report)
- Found that dopamine oxidation mediates mitochondrial and lysosomal dysfunction in human models of Parkinson’s, but not mouse models (Click here to read the research report and click here to read the SoPD post on this topic)
- Identified 7 new genetic risk factors for Parkinson’s – after looking at 26,035 cases of PD and 403,190 controls – most of these new genes have roles in waste recycling (autophagy and lysosomal biology) (Click here to read more about this).
- Published an analysis of blood from 523 individuals (205 with PD) that may provide a novel diagnostic aid for idiopathic Parkinson’s (Click here to read more about this research)
- Found that genetic variants do not appear to have a major impact on severity of Lewy body pathology in people with Parkinson’s (Click here for more on this)
- Discovered that BDNF neurotrophic activities are blocked by alpha synuclein, triggering dopaminergic cell death in Parkinson’s (Click here to read the research report, and click here to read a SoPD post on this topic)
The research event that blew my mind in September was the reporting of more non-invasive gene therapy results. This time the AAV-PHP.B virus was used to rescue a genetic mouse model of Parkinson’s (Click here to read the research report and click here to read the SoPD post on this topic).
In addition to this, there was a report from researchers in Boston and Norway which indicated that the Beta2-Adrenoreceptor agonist, Salbutamol (which is commonly used for the treatment of conditions of the lungs such as Asthma – a common long-term inflammatory condition of the lungs) was associated with decreased risk of developing Parkinson’s disease – literally a 1/3 reduction in risk.
The Norwegian researchers also reported that Propranolol which blocks the Beta2-Adrenergic receptor was associated with a two-fold increase in the risk of developing Parkinson’s disease (see graph below):
The researchers found that Beta2-Adrenoreceptor agonists (like Salbutamol) reduced the production of the Parkinson’s associated protein Alpha Synuclein. This class of drugs is now being further researched and we can hopefully expect more data in the new year (Click here to read the research report and click here to read a SoPD post on the topic).
In clinical news, Voyager Therapeutics announced positive results from their ongoing Phase Ib Trial of VY-AADC01 for advanced Parkinson’s (Click here to read the press release and click here to read the SoPD post on this topic).
We learnt more about the role that diet and nutritional supplements can play in Parkinson’s progression (Click here to read the research report, and click here to read the SoPD post on this topic), and two population-based cohorts showed that dietary vitamin E & Beta-carotene are associated with a lower risk of developing Parkinson’s (Click here to read the research report).
And that was September. The year was flying by. Moving on to:
Lots of major world news stuff happened in October:
- US scientists Jeffrey C. Hall, Michael Rosbash and Michael Young awarded Nobel Prize for physiology or medicine for work on the body clock (October 2nd)
- Nobel Prize for Chemistry awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for their work on cryo-electron microscopy (4th October)
- Spanish government says it will impose direct rule on Catalonia after the region voted for independence in a referendum (October 14th)
- Musician Antoine Dominique “Fats” Domino passed away (24th October)
- New Zealand Labour Party leader Jacinda Ardern (37 years old) is sworn in as Prime Minister of New Zealand, becoming the world’s youngest female head of government (October 26th)
“Jacinda-mania” in NZ
In the world of Parkinson’s research, British charity Parkinson’s UK held their annual research support network conference in Birmingham on 15th October. If you missed it, you can watch it here:
In other Parkinson’s-related news, the research community learnt about:
- A novel protective role for Trehalose against protein aggregation in model of Parkinson’s – while Trehalose is widely considered to be an autophagy (waste recycling) activator, this new research suggested that it was actually an autophagy blocker, but still exhibiting neuroprotective effects through an autophagy-independent mechanism (Click here to read the research report)
- Researchers at Dundee University determining the structure of PINK1 protein and mechanisms of Parkinson’s associated mutations – a better understanding of the structure of the protein will allow for the designing of drugs that target PINK1 more specifically (Click here to read this research report)
- Parkinson’s associated GBA genetic mutation (L444P) enhanced alpha synuclein induced loss of dopamine neurons in models of Parkinson’s – suggesting that GBA deficiency enhances neuronal vulnerability to neurodegenerative processes triggered by increased alpha synuclein levels (Click here to read more about this)
- Functional loss of both LRRK1 & 2 genes resulted in the loss of dopamine neurons in an age-dependent manner (Click here to read more about this)
- A large CRISPR screening study that identified numerous genes required for herbicide (Paraquat) induced cell death – identifying/designing drugs that block these pathways could provide novel treatments for Parkinson’s (Click here to read the research report)
- A LRRK2 kinase inhibitor (GNE-7915) that can rescue mitochondrial DNA damage in a genetic model of Parkinson’s (LRRK2 G2019S) – this is a major area of research for several biotech firms (Click here to read more about this)
- The presence of a protein called TAU being found within foetal cell transplants in people with Huntington’s & Parkinson’s – indicating another protein that may be being passed from the diseased brain to healthy cells (similar to alpha synuclein – Click here for more on this – and click here to read a SoPD post on this topic)
- The better targeting of electrodes with new 8 channel which will allow for steering of stimulation in deep brain stimulation for Parkinson’s (Click here to find out more about this)
In clinical news, Intra-Cellular Therapies started enrolling for a clinical trial of their phosphodiesterase 1 inhibitor called ITI-214 for Parkinson’s – Inhibitors of PDE1 block the breakdown of cyclic nucleotides (cAMP, cGMP). The PDE1 enzyme is highly active in conditions like Parkinson’s (Click here to read the press release)
Swedish biopharma –Bioarctic AB – was granted an EU patent for BAN0805 (alpha synuclein monoclonal antibody), indicating yet another player entering the immunotherapy field for treating Parkinson’s (Click here to read the press release).
Biotech firm Insightec were given FDA approval to initiate a clinical study of MRI-guided Focused Ultrasound for dyskinesia in advanced Parkinson’s – this technique allows for non-invasive destruction of tiny parts of the brain that can provide beneficial effects (Click here to read the press release, and click here to read a SoPD post about MRI-guided Focused Ultrasound)
And all of this was just a fraction of the research that was done in October. Next, on to:
In November, we observed the first known interstellar object: a high velocity asteroid that scientists named ʻOumuamua’ (20th November). And as a new species of orangutan was identified in Indonesia (3rd November) and Prince Harry announced his engagement to actress Meghan Markle (27th November), President Trump toured Asia and then went to war against Lavar Ball over something to do with some shop lifted sunglasses.
As all of this was happening, the Parkinson’s community received some disappointing news: Acorda Therapeutics announced that they were halting recruitment for their phase III clinical trials of their drug Tozadenant (an oral adenosine A2a receptor antagonist) due to reports of sepsis – some of which were fatal (16th November).
And then 3 days later they cancelled the program completely (20th November). The company will analyse the results the phase III safety and efficacy trial – over 90% of the participants in that short, placebo-controlled study (entitled CL-05) have completed that study. It will be interesting to see those results. The company expects to release those results early in the new year.
On a more positive note, the Parkinson’s research community had a lot of new research to digest in November. They read published reports about:
- The S-Nitrosylation (SNO) of Parkinson’s associated PINK1 decreasing the transportation of another Parkinson’s protein, PARKIN, to mitochondria. Researchers suggest that this process may exacerbate the neuronal death involved in Parkinson’s (Click here to read the research report, and click here to read a SoPD post on this topic)
- Anti-ageing protein Klotho rescuing a model of Parkinson’s. This amazing compound apparently functions by alleviating levels of apoptosis (programmed cell death) and oxidative stress (Click here to read more about this)
- Genetic variants associated with Alzheimer’s-related Beta-Amyloid protein clearance are involved in the pathogenesis of dementia in Parkinson’s. In addition, these mutations may also influence the age of onset of the dementia (Click here to read more about this research)
- A novel mouse model of Parkinson’s that reliably recapitulates many aspects of the condition. A GBA genetic mutation in mice that also have an alpha synuclein genetic variants exhibit progressive neurological symptoms (Click here to find out more)
- An analysis of DNA from 1156 Parkinson’s cases & 1679 control subjects indicating that a significant number of rare lysosomal storage disorder gene variants are associated with increased risk of developing Parkinson’s. Lysosomal storage is a critical part of the waste recycling system and reductions in lysosomal function may enhance Parkinson’s susceptibility (Click here to read that report)
- The Agriculture and Cancer cohort study found strong associations between Parkinson’s & exposure to dithiocarbamate fungicides, rotenone, and the herbicides diquat & paraquat – further supporting the role of these chemicals in increasing the risk of developing Parkinson’s (Click here to find out more about this)
- An analysis of the Danish medical registries suggested that tonsillectomy (removal of the tonsils) is NOT associated with increased risk of developing Parkinson’s (especially early-onset – Click here to see the research report)
- How a LRRK2 kinase pathway assay could assist in patient stratification (based on LRRK2 kinase activity). This assay could help with pharmacodynamic & target engagement studies in future LRRK2 inhibitor trials in Parkinson’s (Click here to learn more)
- While LRRK2 is not required for TAU transmission, the Parkinson’s associated G2019S-LRRK2 genetic mutation markedly enhances TAU transmission in mice, suggesting a new role for LRRK2 in Parkinson’s (Click here to read more about this)
- The presence of multiple LRRK2 genetic risk variants are associated with a younger age at onset of Parkinson’s (Click here to read this research report)
In clinical news, a double blind randomised trial suggested that Xeomin injections can improve foot dystonia in Parkinson’s (Click here to read the study results)
Another randomised clinical trial evaluating the use of sodium oxybate for excessive daytime sleepiness & sleep disturbance in Parkinson’s found that it “significantly improved sleepiness and disturbed nighttime sleep both subjectively and objectively” (Click here to read this research report)
Rodin Therapeutics announces research grant support from the Michael J. Fox Foundation to advance novel treatment strategies for Parkinson’s. Rodin’s novel set of brain-penetrant small molecule drugs are designed to “boost pathways that play a critical role in synaptic function while minimising key safety concerns”. They achieve this through HDAC complex selective inhibition, and by doing this Rodin compounds may have an impact on the course of Parkinson’s (Click here to read the press release)
International Stem Cells Corp released six months interim results for the first cohort of Parkinson’s subjects transplanted with stem cells in their Phase I clinical trial – the primary endpoint (safety) was achieved (Click here to read the press release)
Kiwi biotech firm Living Cell Technologies reported that their NTCELL product failed to demonstrate any “statistically significant difference” in a Phase II clinical trial for Parkinson’s (Click here to read the press release)
In December 2017, fanatics in one part of the world excitedly awaited the arrival of the latest installement in the Star Wars saga (15th December – still haven’t seen it, no spoilers please!), while fanatics in another part of the world were given their marching order – the Iraqi military announced that it had “fully liberated” all of Iraq’s territory from “ISIS terrorist gangs” (9th December).
The United States announced that it will move its Israeli embassy to Jerusalem – recognising it as the capital of Israel (6th December). Meanwhile, in Amman, Jordan, officials reported that a former rescue cat named Lawrence of Abdoun was settling into his new role as chief mouser. Lawrence was the first diplo-cat to be appointed by the British Embassy in Jordan.
December was a HUGE month for Parkinson’s research. In just December alone we learnt that:
- A functional MRI brain imaging study of 29 people with Parkinson’s plus freezing of gait (FOG), 28 PWP without FOG and 31 controls indicates altered resting-state brain activity. The researchers found dysfunction in frontal-parietal regions, along with increased inhibitory outputs from basal ganglia of people with Parkinson’s plus FOG, when compared to PWP without FOG and controls (Click here to see more on this)
- Mild hyperbaric oxygen (basically breathing pure oxygen at higher than atmospheric pressures) slows the loss of dopamine neurons in mouse model of Parkinson’s (Click here to read more about this)
- GTPase Rab29 is a master regulator of Parkinson’s‐associated LRRK2, suggesting that inhibitors that block Rab29 binding might inhibit LRRK2 activity and thus offer therapeutic potential for the treatment of Parkinson’s (Click here to learn more about this)
- Alterations in waste recycling (a process called autophagy) can be found in peripheral blood mononuclear cells in people with Parkinson’s (Click here to read the research reporton this finding)
- A clinically available anthelminthic drug called Niclosamide has been identified as an activator of PINK1, a protein that is affected in some cases of Parkinson’s. Clinical testing of this drug for Parkinson’s could be worth exploring (Click here to read more about this).
- Longitudinal brain imaging study of 168 people with newly diagnosed Parkinson’s found that cholinergic basal forebrain atrophy predicts cognitive decline (Click here to read this research report)
- FDA-approved immunosuppressive drug ‘Tacrolimus‘ blocks the activity of a protein called calcineurin and in doing so, it reduces alpha synuclein toxicity in models of Parkinson’s (Click here to read more about this).
- The pro-apoptotic protein “BAD” (great name for a protein involved with cell death huh?) as a potential interacting protein of Parkinson’s associated PINK1 – yet another molecular pathway by which PINK1 may be involved with the regulation of cell death in Parkinson’s (Click here to read the research report)
- The identification of the fundamental characteristics that enable the toxic form of Parkinson’s-associated alpha synuclein (oligomers) to perturb biological membranes and disrupt cellular function (Click here to read more about this)
- An enzyme (a Ubiquitin E3 ligase) called ‘CHIP‘ promotes ubiquitination of Parkinson’s-associated protein PINK1 and it decreases PINK1 steady-state levels, thus suppressing PINK1 protective functions. Could CHIP represent a new therapeutic target for Parkinson’s? (Click here to read the research report)
- The FDA-approved blood pressure drug hydralazine (Apresoline) is an activator of the NRF2/SKN-1 signalling pathway. It was found to reduce oxidative stress in models of Parkinson’s and extend the lives of microscopic worms (Click here to read more on this)
- The most comprehensive genetic study in Parkinson’s-associated Dementia with Lewy bodies (DNA from 1743 DLB patients and 4454 controls) confirmed that APOE, SNCA and GBA genetic risk factors, plus identified a new genetic variant in the CNTN1 gene (Click here to read the research report)
- Pre-treatment with anti-inflammatory compound Tenuigenin protects dopaminergic neurons from inflammation in a mouse model of Parkinson’s via suppression of microglia (Click here for the research report)
- Really deep mapping of mitochondrial deletions in dopamine neurons from two postmortem cases of Parkinson’s indicates the number of deleted mitochondrial DNA species per neuron is substantially higher than previously reported (Click here to see more on this)
- Antidepressant Trazodone (which has previously been indicated as a drug worthy of repurposing – Click here for a SoPD post on this) alleviates both dyskinesia & psychosis in primate model of Parkinson’s, but it worsens motor function which may “limit its tolerability & usefulness in clinical settings” (Click here to find out more)
One of the research reports that caught my eye in December was a MASSIVE genome-wide CRISPR/Cas9 knockout screen study that identified 53 genes that positively or negatively regulate the activity of the Parkinson’s-associated gene PARKIN. The research was conducted by the pharmaceutical company Novartis who are obviously keen on developing drug that regulate PARKIN – a protein involved in both Parkinson’s and cancer (Click here to read this research report, and click here for a SoPD post on this topic)
Another study that was published in December which could have profound implications for the Parkinson’s community suggested that Multiple system atrophy ‘prions’ robustly infect cells with wild-type, A30P, & A53T alpha synuclein mutations, but NOT cells with the E46K mutation. This finding indicates that MSA alpha synuclein prions are distinct from those of idiopathic Parkinson’s (Click here to learn more about this study, and click here to read the SoPD post on this topic)
In clinical news, a Phase II randomised, double-blind, placebo-controlled trial of Camicinal (also known as GSK962040, a gastroprokinetic) in Parkinson’s results in significant reduction in OFF time, significant increase in ON time (Click here to read more about this)
A 1 year Japanese clinical study assessing the safety of using of Inosine in people with Parkinson’s reported that the drug was safe and it also significantly raised urate levels. While the study did not indicate whether there was any improvement in the participants, it did provide more support for the ongoing phase III SURE-PD3 study (Click here to read the research)
Another randomised, double-blind study showed that shorter pulse widths widen the therapeutic window of subthalamic nucleus deep brain stimulation in Parkinson’s without increasing the electrical charge required to obtain the same acute clinical benefit (Click here to read more about this study)
One of the most interesting clinical findings of December (if not the entire year) was that a Phase II randomised clinical trial of 128 people with recently diagnosed Parkinson’s from the ‘Study in Parkinson’s Disease of Exercise’ (SPARX) project found high-intensity (but not moderate) treadmill exercise may impact disease progression (Click here here to read the research report). And just one week later, an independent group of scientists suggested that they may have identified one of the molecules behind the effect: the Parkinson’s associated protein DJ-1. They found that exercise reduced alpha synuclein aggregation and improved motor/cognitive function in a mouse model of Parkinson’s (Click here to read this research report)
Another very exciting clinical announcement in December, came from the biotech company Denali Therapeutics which announced advancement and expansion of their LRRK2 inhibitor clinical trial program for Parkinson’s. Their drug DNL201 achieved >90% inhibition of LRRK2 kinase activity (at peak) in their phase I safety trial (Click here to read the press release, and click here to read a SoPD post on the topic)
A third exciting clinical announcement in December had nothing to do with Parkinson’s: biotech firm Ionis pharmaceuticals announced dose-dependent reductions of mutant HTT protein in their phase I/IIa clinical trial of IONIS-HTTRx for Huntington’s disease. While there was no indication as to whether this treatment actually impacted the disease itself (still too early in the trial for that), it was still very encouraging for the Huntington’s community. In addition, Ionis Pharmaceuticals also has plans for testing Parkinson’s related therapies (Click here to read the press release regarding the Huntington’s disease study)
But the clinical data doesn’t stop there (Like I said, December was HUGE for Parkinson’s research!)
A randomised, double-blind clinical trial of deep brain stimulation of a structure in the brain called the nucleus basalis of Meynert in six people with Parkinson’s dementia was safe, but didn’t improve cognitive symptoms. Interestingly, however, stimulation of this structure may improve visual hallucinations (Click here to read the research report)
Elto Pharma Inc. (a subsidiary of Amarantus Bioscience) has received ‘an Intent to Grant a Patent’ notice from the European Patent Office for Eltoprazine. Elto Pharma is currently setting up a Phase IIb clinical trial for Eltoprazine in Levodopa-induced dyskinesia starting for 2018 (Click here to read the press release about this)
A pilot study of MRI-guided focused ultrasound unilateral subthalamotomy found that this non-invasive procedure was well tolerated and improved motor features of Parkinson’s in people with noticeably asymmetric parkinsonism (Click here to read the research report)
And finally, Acorda Therapeutics resubmitted a new drug application (NDA) to the US FDA for their Parkinson’s product Inbrija – their inhalable L-dopa product. The company had positive phase III results earlier in the year, but their original NDA application was rejected by the FDA, due mostly to manufacturing issues. This has delayed the product reaching the clinic, but now the problems have been resolved, so hopefully inhalable L-dopa will shortly be available. Fingers crossed this time (Click here for the press release).
What does it all mean?
So if you are still reading this, you might be thinking that this post was a pretty crazy idea. Written by an obvious lunatic.
And you’re probably right.
On both counts.
It is far too long (seriously, if you have read all of this post in one sitting, I’m not the only crazy one). It wandered and weaved at times (the months were the only things that flowed). And it certainly doesn’t cover all of the research that has been conducted this year (in fact, this is just a fraction of the >7000 Parkinson’s-related research reports).
But the goal of this post was always psychological.
It was to emphasise the point that there has been quite a bit of Parkinson’s research going over the last 12 months (and there will be even more in 2018). We have learnt a great deal in the last 12 months – from both successes and failures – and I think it is very fair to say that 2017 will go down as a good vintage in the annals of Parkinson’s research history.
I am a bit of a wino.
In particular, I am what is called a ‘Pinotphile’ (but please be very careful how you say that out loud in public).
I don’t buy into the silly culture that surrounds wine tasting (it should only be drunk with food thank you very much), but I am utterly fascinated by the process of ageing a bottle of wine. The metamorphous that the grape juice will undergo over time completely blows my mind.
It is amazing what can be achieved with a little time and the right conditions.
I also appreciate the exclamation point that a good wine can provide to a memorable occasion. And the bigger the occasion, the more important the wine.
That said, I will be toasting the end of 2017 with the 2001 Dry River Pinot Noir.
It’s a magnificent wine, and it’s my last bottle. But why not. That is how impressive I think this year has been for Parkinson’s research.
Here’s to 2017. And to friends.
Finally, in the next post we will discuss what 2018 holds with regards to research efforts. I’ve got a funny feeling that 2018 is going to be a really good vintage as well.
EDITOR’S NOTE #2: The information provided by the SoPD website is for information and educational purposes only. Under no circumstances should it ever be considered medical or actionable advice. It is provided by research scientists, not medical practitioners. Any actions taken – based on what has been read on the website – are the sole responsibility of the reader. Any actions being contemplated by readers should firstly be discussed with a qualified healthcare professional who is aware of your medical history. While some of the information discussed in this post may cause concern, please speak with your medical physician before attempting any change in an existing treatment regime.
In addition, many of the companies mentioned in this post are publicly traded companies. That said, the material presented on this page should under no circumstances be considered financial advice. Any actions taken by the reader based on reading this material is the sole responsibility of the reader. None of the companies have requested that this material be produced, nor has the author had any contact with any of the companies or associated parties. This post has been produced for educational purposes only.
The banner for today’s post was sourced from C0zy
13 thoughts on “2017 – Year in Review: A good vintage”
Thanks for another great post Simon. For me, 2017 will go down as the year I got diagnosed. Thanks for hope you’ve provided.
ISC clinical trial of hpNsc has not been mentioned
Thanks for your comment.
The oversight was a mistake on my part, I simply forgot to mention it – I have added a piece in the November section mentioning their interim report on the Parkinson’s clinical trial.
International Stem Cell Corp is a publicly traded company so I must be careful with regards to my comments, but I will be adding the ISCO’s press release to this review reluctantly. This is because many of the previous disclosures from this company have been very troubling (https://scienceofparkinsons.com/2016/11/17/update-iscc-stem-cell-transplantation-trial/) and their interim report in November contained nonsensical data (based on the company’s own preclinical data). I (and many others in the Parkinson’s research community) have serious concerns about this trial.
As an outsider to the research, but someone who understands tech companies and the promotion of new IP and products, it’s clear that ISCO is giving the sales pitch at every opportunity. Here’s hoping the product is the real deal. If it is, we’d likely see an investment or acquisition from a big player. This would most certainly be preceded by thorough due diligence that would hopefully distinguish reality from the hype. Until then I’m also skeptical.
I will try to hold my tongue here, but much of what you say is probably right.
i found it very encouraging to read about the army of scientists/clinicians who are working on this problem around the globe and from so many different angles. it really does seem that progress is being made. your blog is a highlight in my (boring) life, and i appreciate all the time you put into it. your engaging style of writing and illustrating keeps me reading. i hope you enjoyed that exquisite-sounding wine. now i need to find a blog with other wine suggestions : )
Thanks, Simon, for all your hard work in disseminating the info in understandable form. Happy New Year!
Thanks for your kind message Rosie. Much appreciated.
What beethaven and Rosie said
Great info, keep pushing
Great Post! You are sharing a wonderful post. Thanks and keep sharing.
Nice blog youu have