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Monthly Research Review – September 2018

At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during September 2018.

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


So, what happened during September 2018?

In world news:

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

Source: HuffPost

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

Source: WPLG

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

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

Source: NYTimes (some amazing images on this link)

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

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

Source: Australian

 

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

In September 2018, there were 841 research articles added to the Pubmed website with the tag word “Parkinson’s” attached (5978 for all of 2018 so far). In addition, there was a wave to news reports regarding various other bits of Parkinson’s research activity (clinical trials, etc).

The top 5 pieces of Parkinson’s news

Continue reading

Monthly Research Review – May 2018

At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during May 2018.

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


Before we start: 

Today is the 31st May 2018, which represents the one year anniversary since the passing of Tom Isaacs:

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Tom was one of the co-founders of the Cure PD Trust.

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, (utterly) tireless activist. He firstly walked the entire coastline of the UK to raise money and awareness for Parkinson’s.

tom isaacs

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 and Muhammad Ali, Tom has had the most impact on marshaling scientific research efforts to find a cure for Parkinson’s.

And he did it all with style and humour:

This was a video of Tom in 2009, talking about life with Parkinson’s disease:

Here at SoPD HQ, we were gutted by his passing, and wanted to make a special note here.

 

So, what happened during May 2018?

Continue reading

I’ll have the fish please

We have previously discussed the importance of the right foods for people with Parkinson’s on this blog – Click here for a good example.

Recently, new data from researchers in Sweden points towards the benefits of a specific component of fish in particular.

It is a protein called β-parvalbumin, which has some very interesting properties.

In today’s post, we discuss what beta-parvalbumin is, review the new research findings, and consider how this new information could be applied to Parkinson’s.


A very old jaw bone. Source: Phys

In 2003, researchers found 34 bone fragments belonging to a single individual in a cave near Tianyuan, close to Beijing (China).

But it was not the beginning of a potential murder investigation.

No, no.

This was the start of something far more interesting.

Naming the individual “Tianyuan man”, the researchers have subsequently found that “many present-day Asians and Native Americans” are genetically related to this individual. His bones represented one of the oldest set of modern human remains ever found in the eastern Eurasia region.

Tianyuan caves. Source: Sciencemag

But beyond the enormous family tree, when researchers further explored specific details about his jaw bone (or lower mandible as it is called) they found something else that was very interesting about Tianyuan man:


Title: Stable isotope dietary analysis of the Tianyuan 1 early modern human.
Authors: Hu Y, Shang H, Tong H, Nehlich O, Liu W, Zhao C, Yu J, Wang C, Trinkaus E, Richards MP.
Journal: Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):10971-4.
PMID: 19581579                     (This research article is OPEN ACCESS if you would like to read it)

In this study, the investigators analysed the carbon and nitrogen isotopes found within bone collagen samples taken from the jaw bone of Tianyuan man. In humans, the carbon and nitrogen isotope values indicate the sources of dietary protein over many years of life.

The researchers found that a substantial portion of Tianyuan man’s diet 40,000 years ago came from freshwater fish.

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

Continue reading

Monthly Research Review – April 2018

At the end of each month the SoPD writes a post which provides an overview of some of the major pieces of Parkinson’s-related research that were made available during April 2018.

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


So, what happened during April 2018?

In world news:

  • April 4–15th – The 2018 Commonwealth Games were held in Gold Coast, Queensland, Australia (New Zealand came 5th in the medals tally… not bragging, just saying).

Source: Vimeo

  • April 27th – Kim Jong-un crosses into South Korea to meet with President Moon Jae-in, becoming the first North Korean leader to cross the Demilitarised Zone since its creation in 1953. In initial small steps towards reconciliation, South Korea said it would remove loudspeakers that blare propaganda across the border, while North Korea said it would shift its clocks to align with its southern neighbour.

BFFs? Source: QZ

Source: Plus

  • And finally the city of Trier in Germany is already struggling to keep up with demand for ‘0-euro’ notes, bearing the face of its most famous son and communism’s creator Karl Marx. Sold for 3 euros each, the notes are part of celebrations for his 200th birthday (5th May 1818).

You get what you pay for. Source: DDR

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

Continue reading

Monthly Research Review – January 2018

Today’s (experimental) post provides something new – an overview of some of the major bits of Parkinson’s-related research that were made available in January 2018.


In January of 2018, the world was rocked by news that New Zealand had become the 11th country in the world to put a rocket into orbit (no really, I’m serious. Not kidding here – Click here to read more). Firmly cementing their place in the rankings of world superpowers. In addition, they became only the second country to have a prime minister get pregnant during their term in office (in this case just 3 months into her term in office – Click here to read more about this).

A happy New Zealand prime minister Jacinda Ardine

In major research news, NASA and NOAA announced that 2017 was the hottest year on record globally (without an El Niño), and among the top three hottest years overall (Click here for more on this), and scientists in China reported in the journal Cell that they had created the first monkey clones, named Zhong Zhong and Hua Hua (Click here for that news)

Zhong Zhong the cute little clone. Source: BBC

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

Iron, life force, and Parkinson’s disease

pranaLogo

‘Prana’ is a Hindu Sanskrit word meaning “life force”.

An Australian biotech company has chosen this word for their name.

Recently Prana Biotechnology Ltd announced some exciting results from their Parkinson’s disease research programme.

In today’s post we will look at what the company is doing, the science underlying the business plan, and review the results they have so far.


adpd2017

Source: ADPD2017

At the end of March, over 3000 researchers in the field of neurodegeneration gathered in the Austrian capital of Vienna for the 13th International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (also known as ADPD2017).

crop

The Vienna city hall. Source: EUtourists

A lot of interesting new research in the field of Parkinson’s disease was presented at the conference (we will look at some other presentation in future posts), but one was of particular interest to us here at SoPD HQ.

The poster entitled: Abstract: 104 – PBT434 prevents neuronal loss, motor function and cognitive impairment in preclinical models of movement disorders by modulation of intracellular iron’, was presented by Associate Professor David Finkelstein, of the Florey Institute of Neuroscience and Mental Health (Melbourne, Australia).

Unfortunately the ADPD2017 conference’s scientific programme search engine does not allow for individual abstracts to be linked to on the web so if you would like to read the abstract, you will need to click here for the search engine page and search for ‘PBT434’ or ‘Finkelstein’ in the appropriate boxes.

Prof Finkelstein was presenting preclinical research that had been conducted by an Australian biotech company called Prana Biotechnology Ltd.

promo1

Source: Prana Biotechnology Ltd

What does the company do?

Prana Biotechnology Ltd has a large portfolio of over 1000 small chemical agents that they have termed ‘MPACs’ (or Metal Protein Attenuating Compounds). These compounds are designed to interrupt the interactions between particular metals and target proteins in the brain. The goal of this interruption is to prevent deterioration of brain cells in neurodegenerative conditions.

For Parkinson’s disease, the company is proposing a particular iron chelator they have called PBT434.

What is an iron chelator?

Iron chelator therapy involves the removal of excess iron from the body with special drugs. Chelate is from the Greek word ‘chela’ meaning “claw”.

chelationtherapy_edited-01

Chelator therapy. Source: Stanford

Iron overload in the body is a common medical problem, sometimes arising from disorders of increased iron absorption such as hereditary haemochromatosis. Iron chelator therapy represents one method of reducing the levels of iron in the body.

But why is iron overload a problem?

iron

Iron. Source: GlobalSpec

Good question. It involves the basic properties of iron.

Iron is a chemical element (symbol Fe). It has the atomic number 26 and by mass it is the most common element on Earth (it makes up much of Earth’s outer and inner core). It is absolutely essential for cellular life on this planet as it is involved with the interactions between proteins and enzymes, critical in the transport of oxygen, and required for the regulation of cell growth and differentiation.

So why then – as Rosalind asked in Shakespeare’s As You Like It – “can one desire too much of a good thing?”

Well, if you think back to high school chemistry class you may recall that there are these things called electrons. And if you have a really good memory, you will recall that the chemical hydrogen has one electron, while iron has 26 (hence the atomic number 26).

atoms

The electrons of iron and hydrogen. Source: Hypertonicblog

Iron has a really interesting property: it has the ability to either donate or take electrons. And this ability to mediate electron transfer is one of the reasons why iron is so important in the body.

Iron’s ability to donate and accept electrons means that when there is a lot of iron present it can inadvertently cause the production of free radicals. We have previously discussed free radicals (Click here for that post), but basically a free radical is an unstable molecule – unstable because they are missing electrons.

imgres

How free radicals and antioxidants work. Source: h2miraclewater

In an unstable format, free radicals bounce all over the place, reacting quickly with other molecules, trying to capture the much needed electron to re-gain stability. Free radicals will literally attack the nearest stable molecule, to steal an electron. This leads to the “attacked” molecule becoming a free radical itself, and thus a chain reaction is started. Inside a living cell this can cause terrible damage, ultimately killing the cell.

Antioxidants can help try and restore the balance, but in the case of iron overload iron doctors will prescribe chelator treatment to deal with the situation more efficiently. By soaking up excess iron, we can limit the amount of damage caused by the surplus of iron.

So what research has been done regarding iron content and the Parkinsonian brain?

Actually, quite a lot.

In 1968, Dr Kenneth Earle used an X-ray based technique to examine the amount of iron in the substantia nigra of people with Parkinson’s disease (Source). The substantial nigra is one of the regions in the brain most badly damaged by the condition – it is where most of the brain’s dopamine neurones resided.

d1ea3d21c36935b85043b3b53f2edb1f87ab7fa6

The dark pigmented dopamine neurons in the substantia nigra are reduced in the Parkinson’s disease brain (right). Source:Memorangapp

Earle examined 11 samples and compared them to unknown number of control samples and his results were a little startling:

The concentration of iron in Parkinsonian samples was two times higher than that of the control samples.

Since that first study, approximately 30 investigations have been made into levels of iron in the Parkinsonian brain. Eleven of those studies have replicated the Earle study by looking at postmortem tissue. They have used different techniques and the results have varied somewhat:

  • Sofic et al. (1988)                             1.8x increase in iron levels
  • Dexter et al. (1989)                         1.3x increase in iron levels
  • Uitti et al. (1989)                              1.1x increase in iron levels
  • Riederer et al 1989                         1.3x increase in iron levels
  • Griffiths and Crossman (1993)     2.0x increase in iron levels
  • Mann et al. (1994)                           1.6x increase in iron levels
  • Loeffler et al. (1995)                       0.9   (lower)
  • Galazka-Friedman et al., 1996     1.0   (no difference)
  • Wypijewska et al. (2010)               1.0   (no difference)
  • Visanji et al, 2013                            1.7x increase in iron levels

Overall, however, there does appear to be a trend in the direction of higher levels of iron in the Parkinsonian brains. A recent meta-analysis of all this data confirmed this assessment as well as noting an increase in the caudate putamen (the region of the brain where the dopamine neuron branches release their dopamine – Click here for that study).

Brain imaging of iron (using transcranial sonography and magnetic resonance imaging (MRI)) has also demonstrated a strong correlation between iron levels in the substantia nigra region and Parkinson’s disease severity/duration (Click here and here to read more on this).

Thus, there appears to be an increase of iron in the regions most affected by Parkinson’s disease and this finding has lead researchers to ask whether reducing this increase in iron may help in the treatment of Parkinson’s disease.

How could iron overload be bad in Parkinson’s disease?

Well in addition to causing the production of free radicals, there are many possible ways in which iron accumulation could be aggravating cell loss in Parkinson’s disease.

983245.fig.001

Possible causes and consequences of iron overload in Parkinson’s disease. Source: Hindawi

High levels of iron can cause the oxidation of dopamine, which results in the production of hydrogen peroxide (H2O– a reactive oxygen species – the stuff that is used to bleach hair and is also used as a propellant in rocketry!). This reaction can cause further oxidative stress that can then lead to a range of consequences including protein misfolding, lipid peroxidation (which can cause the accumulation of the Parkinson’s associated protein alpha synuclein), mitochondrial dysfunction, and activation of immune cells in the brain.

And this is just a taster of the consequences.

For further reading on this topic we recommend two very good reviews – click here and here.

Ok, so iron overload is bad, but what was the research presented in Austria?

The abstract:

Title: PBT434 prevents neuronal loss, motor function and cognitive impairment in preclinical models of movement disorders by modulation of intracellular iron
Authors: D. Finkelstein, P. Adlard, E. Gautier, J. Parsons, P. Huggins, K. Barnham, R. Cherny
Location: C01.a Posters – Theme C – Alpha-Synucleinopathies

The researchers at Prana Biotechnology Ltd assessed the potential of one of their candidate drugs, PBT434, in both cell culture and animal models of Parkinson’s disease. The PBT434 drug was selected for further investigation based on its performance in cell culture assays designed to test the inhibition of oxidative stress and iron-mediated aggregation of Parkinson’s associated proteins like alpha synuclein.

PBT434 significantly reduced the accumulation of alpha synuclein and markers of oxidative stress, and prevented neuronal loss.

The investigators also demonstrated that orally administered PBT434 readily crossed the blood brain barrier and entered the brain. In addition the drug was well-tolerated in the experimental animals and improved motor function in toxin-induced (MPTP and 6-hydroxydopamine) and transgenic mouse models of Parkinson’s disease (alpha synuclein -A53T and tau – rTg4510).

These results are in agreement with previous studies that have looked at iron chelator therapy in models of Parkinson’s disease (Click here, here and here for some examples)

Interestingly, PBT434 also demonstrated neuroprotective properties in animal models of multiple systems atrophy (or MSA). Suggesting that perhaps iron chelation could be a broad neuroprotective approach.

The researchers concluded that this preclinical data demonstrates the efficacy of PBT434 as a clinical candidate for Parkinson’s disease. PBT434 shows a strong toxicology profile and favourable therapeutic activity.  Prana is preparing its pre-clinical development package for PBT434 to initiate human clinical trials.

Does Prana have any other drugs in clinical trials?

Yes, they do.

pipeline-assets07-1024x571

Source: Prana

Prana Biotechnology has another product called PBT2.

The company currently has two clinical trial programs for PBT2 focused on two other neurodegenerative diseases: Alzheimer’s disease and Huntington’s disease.

The Alzheimer’s study was called the IMAGINE Trial, but (there is always a ‘but’) recently PBT2 failed to meet its primary endpoint (significantly reducing levels of beta-amyloid  – the perceived bad guy in Alzheimer’s disease) in a phase III trial of mild Alzheimer’s disease. PBT2 was, however, shown to be safe and very well tolerated over the 52 week trial, with no difference in the occurrence of adverse events between the placebo and treated groups.

In addition, there was less atrophy (shrinkage) in the brains of those patients treated with PBT2 when compared to control brains, 2.6% and 4.0%, respectively (based on brain imaging).  The company is tracking measures of brain volume and cognition in a 12 month extension study. It could be interesting to continue that follow up long term to evaluate the consequences of long term use of this drug on Alzheimer’s disease – even if the effect is minimal, any drug that can slow the disease down is useful and could be used in conjunction with other neuroprotective medications.

For Huntington’s disease, the company is also using the PBT2 drug and this study has had a bit more success. The study, called Reach2HD, was a six month phase II clinical trial in 109 patients with early to mid-stage Huntington’s disease, across 20 sites in the US and Australia. The company was aiming to assess the safety profile of this drug in this particular condition, as well as determining the motor and behavioural benefits.

In the ReachHD study, PBT2 showed signs of improving some aspects of cognitive function in the study, which potentially represents a major event for a disease for which there is very little in the way of medical treatments.

For a full description of the PBT2 trials, see this wikipedia page on the topic.

Is Prana the only research group working on iron chelators technology for Parkinson’s disease?

No.

There is a large EU-based consortium called FAIR PARK II, which is running a five year trial (2015 – 2020) of the iron chelator deferiprone (also known as Ferriprox). The study is a multi-centre, placebo-controlled, randomised clinical trial involving 338 people with recently diagnosed Parkinson’s disease.

LOGO_FAIR_PARK_TIME1

The population will be divided into two group (169 subjects each). They will then be assigned either deferiprone (15 mg/kg twice a day) or a placebo. Each subject will be given 9-months of treatment followed by a 1-month post-treatment monitoring period, in order to assess the disease-modifying effect of deferiprone (versus placebo).

Product-14303066240

Deferiprone. Source: SGPharma

As far as we are aware, this FAIR PARK II clinical trial is still recruiting participants – please click here to read more about this – thus it will most likely be some time before we hear the results of this study.

Are there natural sources of chelators?

Yes there are. In fact, many natural antioxidants exert some chelating activities.

Prominent among the natural sources of chelators: Green tea has components of plant extracts, such as epigallocatechin gallate (EGCG – which we have previously discussed in regards to Parkinson’s disease, click here to read that post) which possess structures which infer metal chelating properties.

As we have said before people, drink more green tea!

cup and teapot of linden tea and flowers isolated on white

Anyone fancy a cuppa? Source: Expertrain

So what does it all mean?

Summing up: We do not know what causes Parkinson’s disease. Most of our experimental treatments are focused on the biological events that occur in the brain around and after the time of diagnosis. These include an apparent accumulation of iron in affected brain regions.

Research groups are currently experimenting with drugs that reduce the levels of iron in the brain as a potential treatment for Parkinson’s disease. Preclinical data certainly look positive. We will now have to wait and see if those results translate into the human.

Previous clinical trials of metal chelators in neurodegeneration have had mixed success in demonstrating positive benefits. It may well be, however, that this treatment approach should be used in conjunction with other neuroprotective approaches – as a supplement. It will be interesting to see how Prana Biotechnology’s drug PBT434 fares in human clinical trials for Parkinson’s disease.

Stay tuned for more on this.


UPDATE – 3rd May 2017

Today the results of a double-blind, phase II clinical trial of iron chelator deferiprone in Parkinson’s disease were published. The results of the study indicate a mildly positive effect (though not statistically significant) after 6 months of daily treatment.

Iron1
Title: Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson’s disease
Authors: Martin-Bastida A, Ward RJ, Newbould R, Piccini P, Sharp D, Kabba C, Patel MC, Spino M, Connelly J, Tricta F, Crichton RR & Dexter DT
Journal: Scientific Reports (2017), 7, 1398.
PMID: 28469157        (This article is OPEN ACCESS if you would like to read it)

In this Phase 2 randomised, double-blinded, placebo controlled clinical trial, the researchers recruited 22 people with early stage Parkinson’s disease (disease duration of less than 5 years; 12 males and 10 females; aged 50–75 years). They were randomly assigned to either a placebo group (8 participants), or one of two deferiprone treated groups: 20mg/kg per day (7 participants) or 30mg/kg per day (7 participants). The treatment was two daily oral doses (taken morning and evening), and administered for 6 months with neurological examinations, brain imaging and blood sample collections being conducted at 0, 3 and 6 months.

Deferiprone therapy was well tolerated and brain imaging indicated clearance of iron from various parts of the brain in the treatment group compared to the placebo group. Interestingly, the 30mg/kg deferiprone treated group demonstrated a trend for improvement in motor-UPDRS scores and quality of life (although this was not statistically significance). The researchers concluded that “more extensive clinical trials into the potential benefits of iron chelation in PD”.

Given the size of the groups (7 people) and the length of the treatment period (only 6 months) in this study it is not really a surprise that the researchers did not see a major effect. That said, it is very intriguing that they did see a trend towards motor score benefits in the  30mg/kg deferiprone group – remembering that this is a double blind study (so even the investigators were blind as to which group the subjects were in).

We will now wait to see what the FAIR PARK II clinical trial finds.


UPDATE: 28th June 2017

Today, the research that Prana biotechnology Ltd was presenting in Vienna earlier this year was published:

Prana

Title: The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson’s disease.
Authors: Finkelstein DI, Billings JL, Adlard PA, Ayton S, Sedjahtera A, Masters CL, Wilkins S, Shackleford DM, Charman SA, Bal W, Zawisza IA, Kurowska E, Gundlach AL, Ma S, Bush AI, Hare DJ, Doble PA, Crawford S, Gautier EC, Parsons J, Huggins P, Barnham KJ, Cherny RA.
Journal: Acta Neuropathol Commun. 2017 Jun 28;5(1):53.
PMID: 28659169             (This article is OPEN ACCESS if you would like to read it)

The results suggest that PBT434 is far less potent than deferiprone or deferoxamine at lowering cellular iron levels, but this weakness is compensated by the reduced levels of alpha synuclein accumulation in models of Parkinson’s disease. PBT434 certainly appears to be neuroprotective demonstrating improvements in motor function, neuropathology and biochemical markers of disease state in three different animal models of Parkinson’s disease.

The researchers provide little information as to when the company will be exploring clinical trials for this drug, but in the press release associated with the publication, Dr David Stamler (Prana’s Chief Medical Officer and Senior Vice President, Clinical Development) was quoted saying that they “are eager to begin clinical testing of PBT434”. We’ll keep an eye to the ground for any further news.


FULL DISCLOSURE: Prana Biotechnology Ltd is an Australasian biotechnology company that is publicly listed on the ASX. The information presented here is for educational purposes. Under no circumstances should investment decisions be made based on the information provided here. The SoPD website has no financial or beneficial connection to either company. We have not been approached/contacted by the company to produce this post, nor have we alerted them to its production. We are simply presenting this information here as we thought the science of what the company is doing might be of interest to other readers. 

In addition, under absolutely no circumstances should anyone reading this material consider it medical advice. The material provided here is for educational purposes only. Before considering or attempting any change in your treatment regime, PLEASE consult with your doctor or neurologist. Metal chelators are clinically available medications, but it is not without side effects (for more on this, see this website). We urge caution and professional consultation before altering a treatment regime. SoPD can not be held responsible for any actions taken based on the information provided here. 


The banner for today’s post was sourced from Prana

A new LAG in Parkinson’s

blame-lag-10-copy

We have talked a lot about a protein called Alpha Synuclein on this blog (see our primer page here and our previous post).

It is very closely associated with Parkinson’s disease, given that people with genetic mutations in the alpha synuclein gene are more vulnerable to the condition, AND the protein is a key component in the disease-related circular aggregations (called ‘Lewy bodies’) in the brain. Recently researchers have identified proteins that may be involved with the transfer of Alpha Synuclein between cells – the method by which the disease is believed to be spreading. By blocking or removing these proteins, the researchers have been able to block the transfer of alpha synuclein.

In this post, we will review the research and discuss what this could mean for Parkinson’s disease.


agu20141212-16

Science conference. Source: JPL

At the recent annual Society for Neuroscience conference in sunny San Diego, Dr Ravindran Kumaran, a neuroscientist in the laboratory of Professor Mark Cookson (at the National Institute on Aging in Bethesda, Maryland) stood up and presented data about an interesting protein that few people in the audience had ever heard of.

sfn-title

Title: High-content siRNA screen identifies cellular modifiers of pre-formed alpha-synuclein fibril uptake
Authors: Kumarani R, Fernandez D, Werner-Allen JW, Buehler E, Bax A, Lai-Nag M, Cookson MR.
Source: Click here to see the full abstract

Dr Kumaran and his colleagues had systematically removed the function of each gene – one by one – in cell cultures of human cancer cells, and then measured the efficiency of the cells to absorb (or ‘take up’) the Parkinson’s related protein, alpha synuclein. An absolutely laborious task (remember there are over 20,000+ genes), but when they turned off a gene called TM9SF2, something amazing happened:

The cells absorbed 75% less of the free floating alpha synuclein than normal health cells.

This caused a bit of excitement in the Parkinson’s research community. Here was a potential method of blocking the spreading of alpha synuclein.

The funny thing is: few people had ever heard of TM9SF2, and yet Dr Kumaran then showed that TM9SF2 is in the top 3% of all proteins present in the brain. In fact, the highest concentrations of TM9SF2 are in the substantia nigra and other brain regions that are most affected by Parkinson’s disease.

So you can hopefully understand why some people in the Parkinson’s research community thought that this was a wee bit exciting.

Plus, this data presentation came on the back of another study that was published in September which presented another protein (called Lag3) that exhibited a similar ability to reduce the absorption of alpha synuclein:

lag3

Title: Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3.
Authors: Mao X, Ou MT, Karuppagounder SS, Kam TI, Yin X, Xiong Y, Ge P, Umanah GE, Brahmachari S, Shin JH, Kang HC, Zhang J, Xu J, Chen R, Park H, Andrabi SA, Kang SU, Gonçalves RA, Liang Y, Zhang S, Qi C, Lam S, Keiler JA, Tyson J, Kim D, Panicker N, Yun SP, Workman CJ, Vignali DA, Dawson VL, Ko HS, Dawson TM.
Journal: Science. 2016 Sep 30;353(6307).
PMID: 27708076

In this study, the researchers conducted a screen of 352 proteins that sit on the membrane of cells. They were measuring the level of alpha synuclein binding. They identified three interesting candidates for further investigation, include lymphocyte-activation gene 3 (LAG3), neurexin 1β, and amyloid β precursor-like protein 1 (APLP1).

When the researchers compared the three, they found that by removing LAG3 less alpha synuclein was taken into the cell (by endocytosis) than the other two proteins. In addition, when they increased the amount of LAG3 that a cell produces, they observed a similar increase in the amount of alpha synuclein absorbed by cells.

Next the researchers investigated the transmission of alpha synuclein between brain cells in both normal cells and cells that had no LAG3, and they found not only that LAG3 is required for the transmission, but the absence of LAG3 reduces the damage caused by the transmission.

Finally the researchers used small proteins (antibodies) to bind to and block LAG3, and they observed less transmission and damage caused by alpha synuclein. In their conclusions, the authors pointed out that LAG3 is not the only protein involved with the transmission of alpha synclein – there will be others – but it represents a potential future target for therapeutic intervention in Parkinson’s disease.

So what does this mean?

If the theory of alpha synuclein – that this protein is passed between cells, causing the spread of the disease – is correct, then any agent that can block that transmission should slow down or halt Parkinson’s disease. We have previously talked about vacines and antibodies against alpha synuclein being tested in the clinic (Click here, here and here for more on this), but blocking TM9SF2 and LAG3 represent a new method of preventing the transmission of alpha synuclein. This is very exciting. The more angles of attack that we have for designing a treatment the better our options.

f1-large

Schematic of how LAG3 may be working. Source: Science

We will be watching the field very closely and will keep you posted as new information comes to hand.


The banner for today’s post is sourced from Keepcalm-o-matic

Previous posts

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January 2019
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November 2018
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October 2018
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When you stop going native – tetramers, oligomers, alpha synuclein, mouse model, stablisation compounds
Monitoring Parkinson’s: Doctor, my glasses are listening to us – AudEERING, Emteq, facial expression, voice analysis, hypokinetic dysarthria, basal ganglia, wearable, technology
Grand times in Grand Rapids – Grand Challenges, Rallying, Linked Clinical trials, patient advocacy, prodromal, Van Andel Institute, Cure Parkinson’s Trust
The Bill and Melinda burden study – incidence of Parkinson’s, regional, national, global, Gates, foundation, disease burden, increase

September 2018
Monthly Research Review – September 2018 – research overview, publications, clinical studies, new technology, reviews, videos
Better call Sal(-butamol)? –  Beta, Adrenoreceptor, agonists, antagonists, Propranolol, Salbutamol, asthma, hypertension, tremor, smoking
Exercise: Taking the STING out of Parkinson’s – STING, inflammation, Nimbus Therapeutics, IFM therapeutics, PINK1, PARKIN, mitochondria
EGCG: Anyone fancy a cuppa? – Epigallocatechin Gallate, alpha synuclein, green tea, Promesa study, catechins, antioxidants, aggregation, oligomers
The ADHD study from Utah – ritalin, methylphenidate, retrospective study, PARKIN, PARK2, association, early-onset Parkinson’s
Aspirin: Barking up the right tree? – acetylsalicylic acid,  cyclooxygenase,  Salicylic acid, Spiraea, tyrosine hydroxylase, dopamine
The Kiwi Ketogenic study – clinical study, keto diet, low-fat diet, food, ketone bodies, New Zealand

August 2018
Monthly Research Review – August 2018 – research overview, publications, clinical studies, new technology, reviews, videos
EDITORIAL: BREXIT – a rant about the unforeseen consequences for scientific research of Britain’s decision to leave the European Union
Exenatide: Identifying the responders – clinical trial results, response, treatment, post hoc analysis, study, tremor-dominant, insulin resistant
On the hunt for biomarkers – biorepositories, specimens, biopies, tissue, DNA, RNA, samples, blood, serum, collection
DBS 3.0: Magnetise me? – magnetic field, glass catfish, electromagnetic perceptive gene, transcranial magnetic stimulation, deep brain stimulation
The Science of Constipation – gastrointestinal, discomfort, stool, feces, transit time, gut, laxatives, probiotics, clinical studies, trials, colon, small intestine, rectum
The genetics of Parkinson’s: New mutants – GWAS, genome wide association study, genetic variants, mutations, risk factors, PARK genes
ACT UP: Advocacy is Critical To Undoing Parkinson’s – patient advocacy, HIV, AIDS, direct action, protest
Back to back stimulation – spinal cord stimulation, deep brain stimulation, DBS, freezing of gait, Anticipatory postural adjustment, reactive postural response
Green light in Kyoto – induced pluripotent stem cells, IPS, dopamine neurons, cell replacement therapy, cell transplantation, clinical trial, Japan

July 2018
Monthly Research Review – July 2018 – research overview, publications, clinical studies, new technology, reviews, videos
Keep your sights on lymphocytes – T-cells, helper T-cells, IL-17, Interleukin 17, Regulatory T-cells, Secukinumab, Cosentyx, immune system
New LRRK2 results: Game changer? – LRRK2 inhibitors, Denali therapeutics, Leucine-rich repeat kinase 2, PINK1, DNL-201, DNL-151, LRRK1
Voyager Therapeutics update – clinical trial, gene therapy, AADC, VY-AADC, AAV virus, Phase II, FDA, Type C meeting, BLA
TRIMming aggregates – TRIM21, Huntington’s disease, Huntingtin, TAU, protein aggregation, Prothena, antibodies
Wanted: EEF2K inhibitors – oxidation, NRF2, redox, eukaryotic elongation factor-2 kinase, Longevica Pharmaceuticals, inhibitors, alpha synuclein
A tiny dot with an anti-Parkinson’s plot – graphene quantum dot, graphite, alpha synuclein, Alzheimer’s, beta amyloid, protein aggregation, fibrils, plaques
Lipid issues in ER = ZZZ issues in PD – PINK1, PARKIN, sleep, flies, mitochondria, endoplasmic reticulum, ER, Phosphatidylserine
The Big Hero 6 project – machine learning, artificial intelligence, spiral test, voice test, smart phone app, Intel, Project Paradigm
The Chinese stem cell trial – cell transplantation, clinical trial, embryonic stem cells, ISCO, Transeuro, parthenogenetic stem cells, Bluerock therapeutics, Novo Nordisk

June 2018
Monthly Research Review – June 2018 – research overview, publications, clinical studies, new technology, reviews, videos
Squalamine begets Trodusquemine – alpha synuclein, aggregation, dogfish shark, clinical trial, MSI-1436, ENT-01RASMET, Enterin 
Monitoring Parkinson’s: Putting your finger on it – key stroke, assessment, monitoring, MIT, Madrid, consortium, keyboard, touchscreen
Predicting subtypes of Parkinson’s – BioRxiv,  Parkinson’s Progression Marker Initiative, PPMI, clusters, prognosis, Parkinson Disease Biomarker Program, PDBP
Prothena: Phase I results published – immunotherapy, antibodies, PRX002, clinical trial results, Phase I, alpha synuclein
Is Radotinib ABL to beat Nilotinib? – cancer drug, alpha synuclein, PARKIN, clinical trial, PD Nilotinib, NILO-PD, BRC-ABL inhibitor, Ilyang Pharmaceutical
Blessed are the suppressed – Immunosuppression, immunosuppressant drugs, corticosteroids, Inosine monophosphate dehydrogenase (IMDH) inhibitors, cortisone, hydrocortisone
What do you do with a problem like Exenatide? – NLY01, GLP-1 agonist, Neuraly, activated microglia, reactive astrocytes, mood, anxiety, clinical trial
Don’t get mad! Get NAD! – nicotinamide riboside, Nicotinic acid, Niacin, Nicotinamide, Nicotinamide adenine dinucleotide, GBA, Glucocerebrosidase
Xenon: A bright light for dyskinesias? – inhalation, noble gas, involuntary movements, Levodopa, L-dopa, neuroprotection
Keep an eye on mild TBI – traumatic brain injury, mild, moderate, severe, LRRK2

May 2018
Monthly Research Review – May 2018 – research overview, publications, clinical studies, new technology, reviews, videos
The Mannitol results – Clinicrowd, manna sugar, crowd sourced platform, olfaction, smell, osmolytes, molecular chaperones, HSP-70
To B3 or not to B3, that is the question – niacin, vitamin B3, clinical study, nicotinamide adenine dinucleotide, NAD+, GPR109A, macrophage, M1, M2, anti-inflammatory state
Two birds, one stone? – Tuberculosis, LRRK2, inhibitors, phagocytosis, phagosome, macrophage, PARKIN
Monitoring Parkinson’s: Let’s just sleep on it – IBM, Pfizer, Bluesky project, REM, NREM, clinical trial, Jazz Pharmaceuticals, Polysomnography, Solriamfetol
A vaccine for Parkinson’s – the AFFiRiS update – immunotherapy, antibodies, passive, active, immunity, Prothena, clinical trial, results
DUBstop: Oxford-style – deubiquitinating enzymes, DUB inhibitors, USP30, USP8, University of Oxford, FORMA Therapeutics, Ubiquitin Proteasome Pathway, autophagy, ubiquitin, Hybrigenics Pharma, Mission therapeutics
I’ll have the fish please – β-parvalbumin, calcium, alpha synuclein, protein aggregation, amyloid state, omega-3 fatty acids, docosahexaenoic acid
Planet Researcher to Planet Patient – a commentary/opinion piece regarding life in Parkinson’s research
When SERCA goes berserker – calcium, alpha synuclein, endoplasmic reticulum, ‘sarco/endoplasmic reticulum Ca2+-ATPase, thapsigargin, mipsagargin, G-202, Inspyr Therapeutics
On the importance of Calcium – alpha synuclein, synapse, vesicle, isradipine, action potential, neurotransmitter, STEADY-PD III, clinical trial

April 2018
Monthly Research Review – April 2018 – research overview, publications, clinical studies, new technology, reviews, videos
IBD+TNF AB ≠ PD? – inflammatory bowel disease, LRRK2, anti-TNF therapy, antibodies, inflammation, XPro1595
BIIB054: An immunotherapy update – antibody, Biogen, vaccine, clinical trial, phase I, Spark study, alpha synuclein, protein aggregation, oligomers, fibrils
Could heart failure medication be good for Parkinson’s? – Bumetanide, Bumex, loop diuretic, cholinergic, GABAergic, interneurons, striatum, NKCC1, chloride, antagonist, B&A Therapeutics
Diabetes and Parkinson’s – glucose intolerance, exenatide, bydureon, DPP-4 inhibitors, disease progression, association, epidemiological studies
Ibudilast: A Phosphodiesterase inhibitor – Amyotrophic Lateral Sclerosis, ALS, cAMP, cGMP, Multiple sclerosis, MR1916, dipyridamole, Vinpocetine, ITI-214,  Intra-Cellular Therapies
UDCA 2.0 = TUDCA? – Ursodeoxycholic acid, Ursodiol, Tauroursodeoxycholic acid, bile acid, neuroprotection, clinical trial, repurposing drugs
The aggregating antics of (some) anaesthetics – Inhaled anesthetics, Phox2B, alpha synuclein, propofol, isoflurane, morphine, endoplasmic reticulum, ER stress, unfolded protein response
Is there NOP hope for Parkinson’s? – nociceptin/orphanin FQ, N/OFQ, nociceptin, receptor, ligand, dyskinesias, Blackthorn therapeutics, BTRX-246040, neuroprotection

March 2018
Monthly Research Review – March 2018 – research overview, publications, clinical studies, new technology
Objective measures: Getting smart about pills – Proteus, Medtronic, gastrointestinal tract, constipation, RASMET study, clinical trial, smart pills, digital pills
Making. It. Personal. – clinical trials, drugs, treatment, adaptive, I-SPY, MS-Smart, Stampede, EP-AD
Something is interesting in the state of Denmark – arimoclomol, orphazyme, biotech, ALS, clinical trial, GBA, Glucocerebrosidase, glucocerebroside, SOD1, molecular chaperones
“What’s the evolutionary advantage of Parkinson’s?” – LRRK2-G2019S, flies, vision, traits, contrast sensitivity, Edmond J. Safra lecture, King’s College London, occupation, jobs
The dilemma of success – a hypothetical problem that we may face in the not so distant future
Alpha Synuclein: New Species – AFFiRiS, Prothena, monomers, oligomers, fibrils, Pα-synF, Pα-syn*, antibodies, vaccine, autophagy, mitochondria
Happy birthday: Silverstein Foundation – Jonathan Silverstein, GBA, glucocerebrosidase, Prevail Therapeutics, Alector, resTORbio, REGENXBIO, gene therapy
Voyager Therapeutics: Phase I clinical trial update – VY-AADC, gene therapy, Oxford biomedica, dopamine, AAV virus, clinical trial
The Parkinson’s association-‘s’ – epidemiological study, 23andMe, Michael J Fox Foundation, PredictPD, migraines, obsessive-compulsive disorders, seasonal allergies, anemia, Honolulu Heart Study, liposuction, chin dimples

February 2018
Monthly Research Review – February 2018 – research overview, publications, clinical studies, new technology
An idea: “O Canada” – just an idea about better involving the Parkinson’s community in the research being conducted on PD
Reduce your RAGE as you AGE – glycation, sugar, lewy bodies, Azeliragon, vTv Therapeutics, Advanced Glycation Endproduct, receptor of Advanced Glycation Endproducts,
One black sheep per week – genetic variants, somatic mutations, hippocampus, prefrontal cortex,
Mickey becomes more human? – Atg7, autophagy, genetically engineered mice, mouse models, Lewy bodies, cellular inclusions
Spine-tingling research – spinal cord stimulation, pilot clinical study,
Trazodo or Trazodon’t? – Trazodone, antidepressant, repurposing drugs, neurodegenerative, dyskinesias,
The mystery of caffeine – coffee, metabolites, methylxanthine, adenosine 2A receptor, tea, theobromine
When the zombies are all in your head – cellular senescence, paraquat, herbicide, dopamine neurons, astrocytes, Unity biotechnology

January 2018
Monthly Research Review – January 2018 – research overview, publications, clinical studies, new technology
‘Talking bout my resolution’ – seeking feedback from readers regarding ideas for developing the SoPD website
Inspiration from a church in Mammoth – Jeremiah Pate, Daniela Zarnescu, alpha synuclein, chaperones, protein misfolding
EDITORIAL: That Pfizer news – opinion piece on Pfizer’s decision to terminate Alzheimer’s and Parkinson’s research
FASN-ating PINK research – Vitamin K2, PINK1, Parkin, FASN, TVB-2640, mitochondria, menaquinone, menatetrenone, MK-7, MK-4, Fatty acid synthase
When GCase is away, the GSLs will play – GBA1, Sanofi Genzyme, Ambroxol, Miglustat, Glycosphingolipids, Venglustat
The road ahead: Parkinson’s research in 2018 – expectations, clinical research, clinical trials, 2018, therapeutics, drugs, treatments

December 2017
2017 – Year in Review: A good vintage – annual review of Parkinson’s research
Multiple System Atrophy: A prion disease? – MSA-C, MSA-P, Parkinsonisms, oligomer, fibrils, alpha synuclein,
Novartis focuses on improving PARKIN control – CRISPR-Cas9, proteasome, mitophagy, PARK2, screening study, positive/negative regulators
Inhibiting LRRK2: The Denali Phase I results – Denali Therapeutics, DNL-151, DNL-201, LRRK2 inhibitors, clinical trial, phase I, Leucine-rich repeat kinase 2
James: His legacy (Part 4) – James Parkinson, legacy, history, 200 years, anniversary, Arvid Carlson, William Rutherford Sanders, Charcot, Hornykiewicz, Gowers, Cotzias, Rowntree
A virtual reality for Parkinson’s: Keapstone – Parkinson’s UK, Nrf2, Keap1, biotech, drug development, oxidative stress
PAQ-ing more punch for Parkinson’s – Guadeloupe, French West Indies, Progressive supranuclear palsy, multiple system atrophy, PSP, MSA, Annonaceae, acetogenins, melatonin, Quinoxalines, PAQ, MPAQ, PPQ
The anti-depressing research of antidepressants – Depression, selective serotonin re-uptake inhibitors, tricyclic antidepressants, Amitriptyline, Nortriptyline
Non-invasive gene therapy: “You never monkey with the truth” – GBA, glucocerebrosidase, virus, alpha synuclein, Oxford Biomedica, Prosavin, Adeno-associated virus, AAV-PHP.B
Are Lewy bodies fake news? – cellular inclusions, aggregation, protein, alpha synuclein

November 2017
The EMPRSN talk #1 – public talk, video, Parkinson’s UK, clinical trials
The TAU of Parkinson’s – MAPT, microtubules, alpha synuclein, protein aggregation, genetic risk, haplotype, TRx0237, TauRx Pharmaceuticals,
Beware of the PINK-SNO(W) man! – PARKIN, PINK1, p53, mitochondria, mitophagy, Nitrosylation, S-nitrosylation reaction, environment
The Acorda’s Tozadenant Phase III clinical trials – adenosine A2a receptor antagonist, agranulocytosis, sepsis, Istradefylline,
Editorial: Orphan drug tax credit – rare disease, NORD, OOPD, ORD, Orphanet, EURORDIS, drug development, subsets, Parkinsonism,
James: The man behind the disease (Part 3) – James Parkinson, 200 years, anniversary, history, London Correspondence Society, political radical, geology, paleontology
The LRRK Ascending – LRRK1, LRRK2, PARK8, Dardarin, G2019S,
CRISPR-Cas9: “New CRISPY Parkinson’s research” – gene editing, paraquat, POR, ATP7A, SLC45A4, yeast, alpha synuclein, DJ-1, PARK7, TNX, TIMM9, Editas Medicine,

October 2017
Clinical trials: The Power of One – I-SPY trial, Adaptive clinical trials, N-of-1 studies, caffeine, nicotine, simvastatin, Naftazone
“Three hellos” for Parkinson’s – Trehalose, glucose, autophagy, neuroprotection, inflammation, disaccharide, Junaxo, JNX3001, Bioblast Pharma
Are we getting NURR to the end of Parkinson’s disease? – Nurr1, NR4A2, SA00025, IRX4204, BRF110
Resveratrol’s neglected siblings – stilbenes, Pterostilbene, Piceatannol, NRF2, LRRK2, alph synuclein, stilbenoids
Trying to ‘beet’ Parkinson’s in the developing world – beetroot, red beet, developing world, L-dopa, Levodopa
PACAP and a snail model of Parkinson’s – Pituitary adenylate cyclase-activating polypeptide, G protein–coupled receptors, PAC1, VPAC1, VPAC2, Ac-[Phe(pI)(6), Nle(17)]PACAP(1-27)
A clever new Trk for Rasagiline – DOPAL, MAO-B inhibitors, Alpha Synuclein, BDNF, TrkB,
NIX-ing the PARKIN and PINK1 problem – mitochondria, mitophagy, Parkin, Pink1, Phorbol 12-myristate 13-acetate, NIX,

September 2017
We need a clinical trial of broccoli. Seriously! – Cruciferous vegetables, Brassicaceae, Cruciferae, Glucoraphanin, glucosinolate, Sulforaphane, NRF2, ARE, oxidative stress
Plan B: Itchy velvet beans – Mucuna pruriens – natural, L-dopa, levodopa, Ghana, fava beans
Food for thought! – fish oil, CAM Care, diet, nutritional supplement, iron, coenzymeQ10, PRO-PD, survey, online, soda, beef
AAV-PHP.B: The future is apparently now – non-invasive, gene therapy, Ambroxol, GBA, glucocerebrosidase, virus, alpha synuclein
O’mice an’ men – gang aft agley – Dopamine, oxidative stress, IPS cells, neuromelanin, alpha synuclein, glucocerebrosidase, N-acetylcysteine, NAC, Isradipine
QUATS going on?!? – triclosan, cetylpyridinium chloride, benzalkonium chloride, quaternary ammonium compounds, cetylpyridinium chloride, toothpaste
Voyager Therapeutics: phase Ib clinical trial results – VY-AADC01, AADC, gene therapy, AAV virus, Oxford Biomedica, Neurologix, Ceregene,
Beta2-Adrenoreceptor agonists: Another game changer? – Asthma, Clenbuterol, Salbutamol, Norway, Beta2-Adrenergic receptor,

August 2017
Dear FDA, this is bigly wrong…and you know it! – healthcare regulators, dopamine agonists, impulsivity, gambling, hypersexuality
Hey DJ, I-so-sit-rate! – DJ-1, Park7, Nrf2, oxidative stress, antioxidant, isocitrate dehydrogenase, isocitrate,
Mdivi-1: the small molecule that could? – mitochondria, division, fusion, P110, Kim Tieu, mitochondrial division inhibitor 1, neuroprotection
Self monitoring: there’s something in your eye – self tracking, Proteus, Google, Novartis, Alcon, Dexcom, smart lens, patch, pill
Lrrking in low orbit – ISS, International space station, microgravity, low-Earth orbit, Leucine-rich repeat kinase 2, inhibitors
Dementia with Lewy Bodies: New recommendations – Alzheimer’s disease, care, diagnosis, treatment, recommendations, Robin Williams,
DPP-4: Not a Star Wars character – Dipeptidyl peptidase-4, inhibitors, Sitagliptin, liraglutide, GLP-1, Granulocyte-macrophage colony-stimulating factor, Berberine, Lupeol
Exenatide: An editorial – phase II clinical trial, exendin-4, GLP-1 receptor agonist, Liraglutide, Lixisenatide, dilemma of success, size of effect
Exenatide: One step closer to joblessness! – phase II clinical trial, exendin-4, GLP-1 receptor agonist, gila monster, positive result!
The next killer APP: LRRK2 inhibitors? – Amyloid Precursor Protein, Alzheimer’s, Leucine-rich repeat kinase 2, Tau, Rab, G2019S, genetic mutation

July 2017
Nilotinib: the other phase II trial – abl inhibitor, clinical trial, gleevec, cancer drug, autophagy
The myth of Spring babies – seasonal, birth, schizophrenia, influenza, winter, spring, risk
The Agony and the Ecstasy – dyskinesias, Tim Lawrence, Horizon BBC, Ecstasy, MDMA, UWA-121, serotonin, subthalamic nucleus
Higher socioeconomic status jobs – Centre for Disease Control, CDC, Amyotrophic Lateral Sclerosis, socioeconomic, status, occupation, job, personality, traits
Helicobacter pylori: Unwanted passengers? – microbes, eradication, clinical study, gut, stomach,
DBS2.0: Look mum, no electrodes! – deep brain stimulation, non-invasive, electrodes, temporal interference stimulation, transcranial direct current stimulation,
Improving the SoPD blog 2017 – any thoughts/suggestions? – housekeeping, improvements, blog, website, suggestions, changes, ideas
The Llama-nation of Parkinson’s disease – antibodies, nanobodies, Ablynx, alpha synuclein, llamas
Future of gene therapy: hAAVing amazing new tools – virus, Oxford Biomedica, Prosavin, Caltech, Adeno-associated virus, AAV
Tetrabenazine: A strategy for Levodopa-induced dyskinesia? – tardive dyskinesia, Deutetrabenazine, Huntington’s disease, chorea,
A need for better regulation: Stem cell transplantation – embryonic stem cells, TP53, p53, genetic mutations, variants, cancer, stem cell clinics
Glutathione – Getting the k’NAC’k of Parkinson’s disease – acetylcysteine, NAC, antioxidant, EPI-589, Edison Pharmaceuticals,
The omnigenics of Parkinson’s disease? – genetics, alpha synuclein, height, GIANT, core genes, minor variants

June 2017
The other anniversary: 20 years of Alpha Synuclein – genetic mutation, 1997, Polymeropoulos, Nussbaum, Golbe, G209A, Salerno, Spillantini, Goedert
The autoimmunity of Parkinson’s disease? – alpha synuclein, T cells, autoimmune, MHC complex, autoantibodies, antigen, candesartan, Treg cells
On the hunt: Parkure – Flies, drosophila, cure, repurposed drugs, Scotland, Edinburgh, drug screening, NRF2, Astemizole, antihistamine, Ketoconazole
Cholesterol, statins, and Parkinson’s disease – lipoproteins, lipids, Hydrophilic, lipophilic, PD STAT, clinical trial, simvastatin,
Who am I but my BMI – weight, risk of Parkinson’s, body mass index,
BioRxiv – open access preprints – manuscripts, arxiv, lrrk2, alpha synuclein, publishing
Are Dyskinesias days NAM-bered? – Dipraglurant, mGluR5, negative allosteric modulator, Addex Therapeutics, Michael J Fox Foundation, dyskinesias
The Melanoma drug from MODAG – melanoma, skin cancer, alpha synuclein, Anle138b
Flu jabs and Parkinson’s disease – influenza, virus, vaccination, vaccine
New stem cell transplantation trial for Parkinson’s proposed in China – embryonic stem cells, clinical trial, China, neuronal-precursors
Oleuropein – “surely the richest gift of heaven?” – antioxidant, olive tree, phenylethanoid, hydroxytyrosol, mTOR, autophagy, Alzheimer’s disease

May 2017
James: That essay – James Parkinson, history, essay on the shaking palsy, Paralysis agitans, 200 years, anniversary
Sheffield: flies, fish and a Tigar – UCDA, Ursodeoxycholic Acid, Ursodiol, zebrafish, mitochondria, Pink1, Lrrk2, Tigar, autophagy, mitophagy, Parkinson’s UK
A connection between ALS & Parkinson’s disease? Oh’ll, SOD it! – Amyotrophic lateral sclerosis, Lou Gehrig’s disease, motor neuron disease, free radicals, antioxidants, neuroprotective, Australia, SOD1, Cu-Zn superoxide dismutase, Cu(II)ATSM
Sar-gram-o-stim: The immunostimulation of Parkinson’s disease – immunomodulation, Sargramostim, Nebraska, clinical trial, Treg cells
Shining a light on movement – optogenetics, globus pallidus, movement, motor cortex, Channelrhodopsin, RetroSense
PARK2 and the big C – cancer, mutations, genetics, variants, Parkin, cell division
Rotten eggs, Rotorua and Parkinson’s disease – hydrogen sulfide, New Zealand, neuroprotection, H2S, antioxidants,
New drug approved for ALS – Edaravone, Amyotrophic lateral sclerosis, Lou Gehrig’s disease, motor neuron disease, free radicals, antioxidants, neuroprotective
The Antibiotic and Parkinson’s: Oppsy, they got doxy! – doxycycline, antibiotics, neuroprotection, 6-OHDA, Alexander Fleming,
Trying to digest gut research – microbiome, vagotomy, gut, gastrointestinal system, microbiota

April 2017
Improving Patient Education – Introducing Eirwen Malin – Patient education, Winston Churchill Memorial Trust, fellowship, Eirwen Malin, USA, Argentina,
Wearable Tech 4 Parkinson’s – self tracking, smart phone apps,
Stress and Parkinson’s disease – cortisol, stress, hydrocortisone, adrenal gland,
Old dogs, new tricks – repurposing drugs for Parkinson’s – Dibenzoylmethane, Trazodone, Alzheimer’s, neurodegeneration, prion, repurposing drugs, eIF2alpha, PERK
Iron, life force, and Parkinson’s disease – Iron overload, Chelator therapy, Prana Biotechnology, PBT434, ADPD2017
On astrocytes and neurons – reprogramming for Parkinson’s – Yamanaka, IPS cells, induced pluripotent stem cells, Sweden,
An Ambroxol update – active in the brain – Ambroxol, GBA, glucocerebrosidase, lysosomes, clinical trial, update, genetic mutation
Stimulating research in London (Canada) – spinal cord stimulation, Miguel Nicolelis, Duke, Mandar Jog, Western University, clinical study
Editorial: Putting 200 years into context – 200 year anniversary, James Parkinson, research, science, context, alpha synuclein, GBA
Milestones in Parkinson’s disease research and discovery – 200 year anniversary, James Parkinson, research, science, clinical trials, discovery, Frank Church.
The Enlightened Mr Parkinson – author, interview, Cherry Lewis, James Parkinson, 200 year anniversary,
Hepatitis – Parkinson’s goes viral? – virus, hepatitis B, hepatitis C, Friedrich Heinrich Lewy, Lewy bodies, Negri bodies, rabies, post-encephalitic Parkinsonism, Taiwan, alpha synuclein,
James: The man behind the disease (Part 1) – 200 year anniversary, James Parkinson,

March 2017
ADHD and Parkinson’s disease – Attention deficit hyperactivity disorder, dopamine, ritalin, methylphenidate, echogenicity, Park2, Parkin
Resveratrol: From the folks who brought you Nilotinib – red wine, antioxidants, sirtuins, grapes, Alzheimer’s, clinical trial, Parkin, Park2
A new theory of Parkinson’s disease – Ole Isacson, threshold, ascending, Simone Engelender, Braak, alpha synuclein, Lewy bodies, theory
A yeast model of Parkinson’s disease – Susan Lindquist, microorganism, yeast, genetics, RAB1, Nedd4, Yumanity
The Journal of Parkinson’s disease – special issue – 200 year anniversary, discoveries, special issue, OPEN ACCESS, L-dopa, history DBS, cell transplantation
The red headed mice of Boston – red hair, ginger, melanoma, MC1R, Nurr1, melanocortin-1 receptor

February 2017
Phase II trial launched for Nilotinib – cancer drug, Nilotinib, Georgetown University, clinical trial, phase II, Tasigna,
New kiwi research in Parkinson’s disease – Pericytes, tunneling nanotubes, alpha synuclein, lewy bodies, disease spread, New Zealand,
How pigs are helping with Parkinson’s disease – NTCELL, Living cell technologies, LCT, encapsulated cells, implantation, cerebrospinal fluid, choroid plexus, clinical trial,
Confirmation about that gut feeling? – microbiome, microbiota, gut, gastrointestinal tract, microorganisms, bacteria, sequencing
Pink flies in Leicester at it again – mitochondria, PINK1, PARKIN, flies, Leicester, ATF4
HIV and Parkinson’s disease – AIDS, HIV, virus, AIDS dementia complex, lentivirus, HAART
Busy day for Parkinson’s – 9/2/2017 – Blood test, diagnosis, neurofilament light chain, Nfl, Acorda therapeutics, inhalable L-dopa, clinical trial, phase 3
George H and Vascular Parkinsonism – mini stroke, George HW Bush, syndrome, Vascular, Arteriosclerotic, Parkinsonism, diabetes, high blood pressure,  Macdonald Critchley,
On bans and boycotts – editorial, travel ban, Executive Order 13769, conferences, SfN,
PARIS is always a good idea – PARIS1, Pink1, Parkin, mitochondria,
Something ‘new and fresh’ from Korea – Kainos, Korea, Clinical trial, FAF1, KM-819, apoptosis, inhibitor

January 2017
Parkinson’s 101 (care of Parkinson’s UK) – what is Parkinson’s, clinical trial, drug design, videos, Michael J Fox, Parkinson’s UK
A smartphone application for Parkinson’s disease – umotif, monitoring, technology, clinical study,
An Update from Voyager Therapeutics trials for Parkinson’s – AADC, gene therapy, clinical trial, update,
The Dogfish solution for Parkinson’s – dogfish, Spurdogs, Mud shark, Squalide, Squalamine, alpha synuclein, MSI-1436
Niacin rich diets for Pink flies – Pink1, early onset Parkinson’s, Niacin, NAD+, mitochondria, nicotinamide, PARP,
An interesting commentary on the interpretation of the Nilotinib trial results – Nilotinib, clinical trial, MAO-B inhibitors, DOPAC, HVA
NRF2 and Parkinson’s disease – antioxidants, transcription factor, Antioxidant response elements, alpha synuclein, Lrrk2, Ayurveda, Curcumin, turmeric
Improving the SoPD blog – any thoughts? – house keeping post, requesting feedback

December 2016
The road ahead – Parkinson’s disease research in 2017 – clinical trials, key research areas, slowing the disease, basic biology, replacing lost cells, early detection
Update – Mannitol and Parkinson’s disease – Manna, sweetener, CliniCrowd, Israel, social impact,
Mmmm, Chocolate – xocolātl, cacao, β-phenylethylamine, Kuna indians, Panama, white chocolate, dark chocolate
Blood transfusions and Parkinson’s disease – Blood, transfusion, prion, Alzheimer’s
PREP-ing to treat Parkinson’s disease – prolyl oligopeptidase, PREP, serine protease, inhibitors,
A drug from Kalamazoo – Diabetes, Metabolic Solutions Development, MSDC-0160, Exenatide,
The biology of immortality and Parkinson’s disease – Shinya Yamanaka, IPS cells, regeneration, life extension
A brave new world: 21st Century Cures Act – Obama, FDA, new law, regulator, CDC
Gene therapy in Parkinson’s disease – virus, VY-AADC01, Voyager therapeutics, Aromatic L-amino acid decarboxylase, AADC, clinical trial,
Milk (Yes, milk) and Parkinson’s disease – milk, heptachlor epoxide, Honolulu Heart Study,
Gut reaction to Parkinson’s disease – microbiome, microglia, antibiotics, clinical study, Minocycline

November 2016
A new LAG in Parkinson’s – alpha synuclein, TM9SF2,  Lag3, lymphocyte-activation gene 3, disease progression
Get more EGCG. Drink green tea – green tea, alpha synuclein, EGCG, Epigallocatechin Gallate, monomers, oligomers, fibrils, Lewy bodies
Update – ISCC Stem cell Transplantation trial – SFN, cell transplantation, clinical trial, Melbourne, Australia, International Stem Cell Corporation, ISCO, hpNSC
Something different – Government funding for Parkinson’s research – Trump, US elections, BREXIT, research funding, EU, science funding
Prothena reports Phase 1b results for Parkinson’s immunotherapy – Affiris, clinical trial, passive immunity, Prothena, PRX002, vaccine, antibodies
The benefits (???) of Antioxidants – clinical trial, Coenzyme Q, free radicals, orac, oxidation, vitamins

October 2016
Interesting reading – Nature, prion, lewy bodies, transplantation
Inhaling L-dopa – inhaler, Arvid Carlsson, Oleh Hornykiewicz, Levodopa, George Cotzias, Acorda Therapeutics,
PAMs for Parkinson’s – Prexton, PXT002331, globus pallidus, mGluR4 positive allosteric modulator, dyskinesias, clinical study
The curious case of Bulgarian Gypsies and the incidence of Parkinson’s disease – incidence, statistics, Amish, population, disease burden, Japan

September 2016
Cannabis and Parkinson’s disease – marijuana, medicinal use, clinical studies
The mystery deepens – Melanoma and Parkinson’s disease – skin cancer, genetics
First film footage of Parkinson’s disease – Arthur Van Gehuchten, cinematography, Youtube, Lancet
Update: Stem cells trial for Parkinson’s disease – cell transplantation, clinical trial, Melbourne, Australia, International Stem Cell Corporation, ISCO, hpNSC
Vaccine for Parkinson’s – AFFiRiS update – clinical trial, vaccination, alpha synuclein, antibodies, Austria
On year in – anniversary, happy birthday, 12 months
Game changer for Alzheimer’s – antibodies, clinical trial, Aducanumab, beta-amyloid, alpha synuclein, Biogen

August 2016
Is there something in my eye? – eyeball, retina, veins, arteries, diabetes, Rosiglitazone
Nilotinib update – new trial delayed – Nilotinib, cancer drug, delayed clinical trial
Coffee and Parkinson’s disease it’s not just caffeine – coffee, caffeine, Quercetin, flavonoid

July 2016
Identical twins and Parkinson’s disease – Jeff and Jack Gernsheimer, GBA, Lrrk2, monozygotic, dizygotic, iPS cells, epigenetics
Pesticides and Parkinson’s disease – Farming, insecticides, rotenone, ground water, fungicides
Juvenile-onset Parkinson’s disease – PARK genes, Henri Huchard, Parkin, DJ1, Pink1, PODXL
Editorial note – Cambridge University, Stem cells, institute, Wellcome Trust, #MyView, awareness campaign
Traumatic brain injury and Parkinson’s disease – an association – traumatic brain injury, loss of consciousness, Alzheimer’s disease, Dementia pugilistica
Bees! Bees! Hark to your bees! – clinical trial, bee venom, Apitoxin, Apamin, Calcium channels
Nilotinib and Parkinson’s disease: an update – cancer drug, clinical trial, Tasigna, Novartis, leukemia, CML, autophagy, lysosome, c-Abl inhibitors
The GDNF Trial (Bristol) initial results – Glial cell-derived neurotrophic factor, GDNF, neurotrophic, MedGenesis, Bristol, Clinical trial, Parkinson’s UK, Cure PD Trust,
A gut feeling about gut feelings – vagotomy, Movement Disorder meeting, Berlin, Swedish, Danish, Norwegian

June 2016
New criteria for Parkinson’s disease – diagnosis, criteria, movement disorder
Your appendix and Parkinson’s disease – Appendectomy, alpha synuclein, gut, intestines, bacteria
Muhammad Ali (1942-2016) – famous, boxer, sports

May 2016
A change of dogma for Alzheimer’s disease? – beta amyloid, alpha synuclein, plaques, tangles, protein, aggregation, bacteria, microbes
The Autistic spectrum and Parkinson’s disease – Autism, aging, risk, incidence, PARK2, neuroleptics
Manna from heaven? Mannitol and Parkinson’s disease – alpha synuclein, sweetener, sugar, protein aggregation
The debate surrounding a new Stem cell transplantation trial for Parkinson’s – cell transplantation, clinical trial, Australia, International Stem Cell Corporation, ISCO, hpNSC
Finding PARK16 – PARK genes, genetics, ADORA1, familial
Blood test for Parkinson’s disease? – mitochondria, hyperactivity, clinical study, diagnosis

April 2016
An update on the connection between Melanoma and Parkinson’s disease – somatic mutations, PARK genes, Lrrk2, skin cancer
Helicobacter pylori and Parkinson’s disease – gut, intestines, microbes, bacteria, ALS-PDC, BMAA, Guam
Older siblings and Parkinson’s disease – brother, sister, Sweden, ALS, Schizophrenia
The Parkinson’s UK 2016 Gretschen Amphlet Memorial Lecture – Cambridge, Prof Barker, Parkinson’s UK, public lecture, cell transplantation, clinical trials
Something different – recognising a birthday – James Parkinson, anniversary, photo, portrait, Jean-Martin Charcot
Chromosome 22 and Parkinson’s disease – genetics, 22q11.2 deletion syndrome, DiGeorge syndrome, risk

March 2016
And now spit! – saliva, test, diagnosis, alpha synuclein
Another connection between skin and Parkinson’s disease – Rosacea, antibiotics, dermatitis
Does the age of onset make a difference? – statistics, demographics, early onset, juvenile Parkinsonism, Henri Huchard
Herpes Simplex virus and Alpha-Synuclein – immune system, antibodies, virus
Disco-needs-ya – the science of dyskinesias – involuntary movements, L-dopa, Chorea, Dystonia,

February 2016
A sense of (and the science of) smell – olfactory function, smell
Diagnosed 2500 years ago? No problem – India, Ayurveda, Kampa vata, Mucuna pruriens, L-dopa
Cleaning up with Ambroxol – Glucocerebrosidase, GBA, Ambroxol, clinical trial
Diabetes, Monster saliva, and Parkinson’s disease – glucose tolerance, diabetes, insulin, Gila monster, Exenatide, GLP-1 agonist, clinical trial
Something lrrk-ing in the water… – Lrrk2, Phosphorylation, urine, diagnostic test,
Brain (not Heart) warming research – warm brain, temperature
The science of focused ultrasound therapy – clinical trial, ultrasound, thalamotomy, pallidotomy
New Research – on how movement is controlled – basal ganglia, thalamus, direct/indirect pathways, optogenetics, dopamine
Improving diagnosis – autoantibodies, DATscan
New research – new targets of Lrrk2 – Lrrk2, Sergey Brin, dardarin, rab proteins

January 2016
New research – the disorder of Alpha Synuclein – monomeric, αlpha synuclein, protein aggregation
The vulnerability of dopamine cells in the brain – midbrain, dopamine, substantia nigra pars compacta, SNC, ventral tegmental area, VTA
New research – Urate and Parkinson’s – Ammonia, Inosine, antioxidant, blood
New Research -Shared genetic features – DNA methylation, common genetic markers, neurodegenerative disease
Viruses and Parkinson’s – a hit and run story? – influenza, H1N1, encephalitis lethargica, Spanish flu, H5N1, hepatitis C, chickenpox
The Placebo effect and Parkinson’s disease – dopamine, placebo, randomized double-blind study
Cell transplantation – Replacing what has been lost – Colorado, Columbia, Tampa Bay, clinical trials, Transeuro, Embryonic stem cells, lewy bodies

December 2015
GDNF and Parkinson’s disease – Synergen, glial cell-derived neurotrophic factor, neurturin, persephin, artemin, gene therapy, MedGenesis, NSgene, Amgen, Bristol, clinical trial
A call to arms – Parkinson’s, anniversary, 200 years
Parkinson’s disease and the cancer drug – Nilotinib, Tasigna, Novartis, leukemia, CML, autophagy, lysosome, clinical trial, c-Abl inhibitors
“Red hair, sir, in my opinion, is dangerous” – red hair, fair skin, frequency, incidence, MC1R

November 2015
The difference between men and women – frequency, incidence, Japanese, testosterone, Cox2
The Honolulu Heart Study – Japanese, smoking

October 2015
The smell of Parkinson’s disease – Joy Milne, Perth, Scotland, sebum, skin

September 2015
Do you have trouble lying? Parkinson’s and Personality traits – metabolism, prefrontal cortex
Vaccination for Parkinson’s disease – vaccine, alpha synuclein – AFFiRiS, clinical trial, vaccine, alpha synuclein, Prothena, Lewy body
Alzheimer’s news – prion, amyloid beta,
Melanoma and Parkinson’s – skin cancer
A gut feeling – intestines, stomach, vagus nerve, vagotomy