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

More importantly, in the world of Parkinson’s research, scientists reported that:

Mitochondrial targeted HSP90 inhibitor, Gamitrinib-triphenylphosphonium an anti-cancer agent – induces Parkinson’s-associated PINK1/Parkin-dependent waste disposal of unhealthy mitochondria (mitophagy) ( to read the research report).

 

Mutations in glycosphingolipid (GSL)-degrading glucocerebrosidase (GBA) gene is a risk factor for Parkinson’s. Reducing GSLs in PD patient neurons (with & without GBA mutations) in culture reduced pathology & restored normal alpha-synuclein function (Click here to read the report and click here to read the SoPD post on the topic).

 

Subthalamic nucleus deep brain stimulation may have the potential for improving posture in people with advanced Parkinson’s ( to read this research report and click here for the  explanation ).

 

Deep brain stimulation of the subthalamic nucleus. Source: Health-innovations

Accumulation of PARIS (a protein which interacts with several Parkinson’s associated proteins) might distort the balance of glucose metabolism. An inhibitor of PARIS might be a useful thing… I’m just saying ( to read the research report). We have previously discussed PARIS on the website regarding other research on this topic (Click here to see that post).

 

Prion-like propagation of the toxic form of Parkinson’s-associated protein alpha synuclein is regulated by the FcγRIIB-SHP-1/2 signalling pathway in neurons ( to read the research report).

 

A bioinformatics approach for repositioning drugs for Parkinson’s suggests that #1 Estradiol (a steroidal estrogen), #2 Resveratrol (a stilbenoid), followed by three retinoids. Food for thought, but please discuss with your doctor before changing your diet or treatment regime ( to see this research). There is also a post on the SoPD website regarding Resveratrol (Click here for that post).

 

New clinical study found that 108 people with Parkinson’s had significantly lower blood levels of caffeine and 9 of 11 byproducts of caffeine in their blood than 31 people without Parkinson’s… even if they consumed the same amount of caffeine! Is caffeine in the blood a new biomarker for Parkinson’s? ( to see more about this research, and click here for a previous SoPD post on Caffeine).

Caffeine. Source: Medium

High hopes for CRISPR-Cas9 gene editing technology suffered a set back as researcher found that more than 65 percent of the people tested carried antibodies for the two most commonly used Cas9 proteins. Immunity could mean that CRISPR-based treatments won’t work in these folks. This immunity probably results from Cas9-containing bacteria infecting our bodies and our immune system responding ( to read the research pre-print manuscript).

 

Chinese researchers find that Parkinson’s-associated protein synaptotagmin-11 interacts with another PD-associated protein: PARKIN. They also found that this interaction plays a critical role in the PARKIN-linked neurotoxicity. PARKIN deficiency shown to cause synaptotagmin-11 accumulation and subsequent neurodegeneration. Reducing synaptotagmin-11 reverses this neurotoxicity. Novel therapeutic target? ( to read more on this).

 

Biotech company Axovant Sciences announced negative results for Intepirdine (selective 5-HT₆ receptor antagonist) in Phase IIb HEADWAY & pilot Phase II Gait and Balance Studies for people with Lewy bodies dementia ( to read the press release).

 

Source: Axovant Sciences

LRRK2 inhibitor, PFE-360, being developed by Lundbeck for Parkinson’s causes morphological changes in the kidneys of mice after 2 weeks of treatment, BUT this is partially reversible after 30 day treatment-free period ( to read the research report and click here to read a SoPD post about LRRK2 inhibitors).

 

The results of a longitudinal study of 544 subjects demonstrates a slower decline in motor features of Parkinson’s among those with LRRK2 G2019S genetic variant ( to read more on this).

 

More data was published suggesting that GBA deficiency (due to L444P GBA genetic variant) and the accompanying accumulation of alpha synuclein protein renders dopamine neurons more susceptible to neurotoxic model of Parkinson’s ( to read more about this).

 

Smell test results suggest that differential discriminatory power of individual items is NOT conserved across independent Parkinson’s cohorts, arguing against selective hyposmia in Parkinson’s ( to find out more about this).

 

Source: Vrzone

Further evidence that maintaining GBA activity and reducing glycosphingolipids are important in reducing the misfolding and aggregation of alpha synclein protein in Parkinson’s ( to read more about this).

 

Transcranial ultrasound indicates that hyper echogenicity of substantia nigra (a region of the brain involved in Parkinson’s) is related to dysfunction of iron metabolism. It occurs at more advanced stages of the condition, with more severer motor symptoms ( to find out more about this).

 

The presence of shared LRRK2 genetic variants in both Crohn’s Disease and Parkinson’s provides insight into underlying mechanisms and potential treatments ( to see the research report).

 

Two distinct populations of glutamatergic excitatory neurons in the midbrain control speed & gait selection ( to read more about this).

 

New brain imaging research suggests that the degeneration observed in Parkinson’s may originate in subcortical regions and spreads along neural networks to the overlying cerebral cortex ( to read more on this).

 

Source: Twitter

Lack of Parkinson’s-associated PINK1 alters the response of glial cells (supportive cells) in the brain and enhances inflammation-induced neuronal cell death ( to read the research report).

 

The first in vivo evidence that Parkinson’s associated PINK1 is detectable at basal levels. Analysis of endogenous levels suggest that loss of PINK1 does not influence basal mitophagy ( to read the research report). This result was verified a few days later by another lab (Click here to read the preprint manuscript).

 

Smoking to known to reduce one’s risk of developing Parkinson’s, but this inverse association between smoking and Parkinson’s is less pronounced in people with genetic variations in both RXRA-rs4240705 and SLC17A6-rs1900586 ( to read more about this).

 

Analysis of gut bacteria that markedly increased dopamine neuron cell loss in mice suggest a role for ‘proteus mirabilis’ in the pathogenesis of Parkinson’s ( to find out more about this).

 

Deep brain stimulation of the subthalamic nucleus represents a one method of alleviating troublesome symptoms in Parkinson’s. Researchers in the Netherlands have analysed 65 cases to identify the ‘hotspot’ for placing electrodes ( to read more about this).

 

Scientists discovered that two key cellular structures, mitochondria & lysosomes, come into direct contact with each other in the cell to regulate their respective functions – major implications for Parkinson’s ( to find out more about this).

 

Meta-analysis review of data points towards a Parkinson’s personality – apparently novelty seeking and extraversion are inversely associated with PD ( to read more about this study).

 

Personality. Source: Moneypenny

Zombie astrocytes. Do I need to say more?

Researchers found that postmortem Parkinson’s brain samples display increased astrocytic senescence. They also reported that cultured human astrocytes exposed to paraquat become senescent. And they found that clearance of senescent cells mitigates cell loss in a mouse model of PD ( to read the research report).

 

Parkinson’s UK announces it is funding final preclinical studies of NLX-112, a novel serotonin 5-HT1A receptor agonist for the treatment of L-DOPA-induced dyskinesia in Parkinson’s. If found to be effective on dyskinesias preclinically, this drug could progress directly to phase II clinical trials as it has been phase I tested already ( to read the press release).

 

Experimental Parkinson’s treatment Ambroxol is a GCase chaperone, but researchers have found that it also acts on other pathways, such as mitochondria, lysosomal biogenesis, and the secretory pathway ( to read the research report).

 

Ambroxol. Source: Skinflint

Voyager Therapeutics announced FDA clearance to begin dosing participants for their pivotal Phase 2-3 clinical trial of VY-AADC for advanced Parkinson’s. This is a gene therapy approach for PD ( to read the press release).

 

Green tea compound (-)-Epigallocatechin-3-gallate (EGCG) has neuroprotective effects in a model of Parkinson’s (MPTP) and it may exert this effect through modulating peripheral immune response ( to find out more about this).

 

Reducing striatal glutamate signalling may improve L-dopa treatment. Locally applied AMPAR or NMDAR antagonist reduce glutamate signalling which stabilises dopamine-induced activity increases and decreases in a primate model of Parkinson’s ( to read the research report).

 

A randomised, double-blind phase II study of Zonisamide (adjunctive to levodopa) improved Parkinson’s features in people with dementia with Lewy bodies without worsening cognitive function or psychiatric symptoms ( to read more about the results of this clinical trial).

 

Removal of prolyl oligopeptidase (or PREP) reduces Parkinson’s-associated alpha synuclein toxicity in cell and mouse base models of PD. Increasing levels of PREP enhances alpha synuclein toxicity. A very interesting therapeutic target ( to find out more).

 

Further evidence that there is an impairment in vocal motor control in Parkinson’s. The findings of a new study indicate that there may be an impairment in the adaptive control of voice in PD ( to read the research report).

 

A 3-month double-blind, randomised sham-controlled study of a repetitive deep transcranial magnetic stimulation on Parkinson’s fails to demonstrate an advantage for real treatment over sham treatment ( to find the research report).

 

Deep transcranial magnetic stimulation. Source: Wikipedia

By reducing levels of mitochondria‐localized protein ‘p13‘, researchers made mice resistance to toxin‐induced motor deficits & to the loss of dopaminergic neurons in the substantia nigra. New target for Parkinson’s? ( to find out more).

 

Miniaturized neural drug delivery system (or MINDS) are cannulas (made up of several tubes, each approx. 30 micrometers in diameter), that can be implanted in the brain and can deliver different types of medications. Implications for Parkinson’s?

Interesting possibilities for this: – multiple drugs could be administered (or tested: think adaptive clinical trials) – no blood brain barrier issues – targeted to specific brain structures – limited off-target peripheral side effects. Verdict: Very cool! ( to find out more).

Icariin, a single active component extracted from the Herba Epimedii, reduces dopaminergic neuronal loss & microglia-mediated inflammation in models of Parkinson’s (Click here to read the research report).

 

Blood serum from 73 people with Parkinson’s – divided into groups with early PD, late PD with dyskinesia & late PD without dyskinesia – demonstrates significant differences in free amino acid profiles. Interestingly they “observed some significant differences amongst the groups with respect to concentrations of alanine, arginine, phenylalanine & threonine, although no significant differences were observed between patients with advanced PD with & without dyskinesia” (Click here to read the research report).

 

A UK-based study confirms the influence of the Parkinson’s-associated GBA mutations on the age of onset, disease severity & motor features in PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline ( to read more about this work).

 

Pisa Syndrome (PS) occurs when the trunk of the body leans to one side – a common feature in Parkinson’s. New research suggests verticality misperception (miscalculation of one’s vertical position to the horizon) is a potent risk factor for PS ( to read more about this).

 

The US National Institute of Health (NIH) Accelerating Medicines Partnership for Parkinson’s (AMP PD) has been announced. The NIH is teaming with the government, biopharmaceutical, life science and non-profit organisations to overcome obstacles for advancing promising treatments for Parkinson’s ( to read the press release).


This post has been a real experiment.

These were the main Parkinson’s-related research highlights for the month of January 2018. Much of the material used here was collected from the SoPD Twitter feed (and there is a lot more posted there each day). I’m not sure I like the shopping list format, so I might have a play with it before the February’s review.

I have tried to incorporate readers’ request of having a label to indicate what sort of research each piece of news is related to (Novel drug target, clinical study, etc). I wanted to keep those labels relatively generic, but I’m not really sure I like the current style. I’ll go away and do some more experimenting with it.

For now, there is hopefully something of interest in the list above for everyone. Any feedback would be greatly appreciated.

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22 comments

  1. jonathanbromley

    Thanks for this brilliant roundup. Still don’t know how you find the time to gather, digest and present this information, but it’s gold dust for non-specialists who are keen to stay aware of research developments. If you can keep this going, the archived stream of highlights and links will be a wonderful resource.

    A few random suggestions here…

    Personally I think that what you describe as a “shopping list” is pretty much right for this sort of thing. I don’t think there’s much benefit in trying to catalogue it – though there may be some value in adding category-style tags to each item (in plain text) to aid searching when the archive gets bigger. Inevitably you have a huge zoo of WordPress tags on this post, which reduces the selectivity of searches. Internal text tags might make it easier to search within the content.

    The idea of labels/icons for broad classes of content is fine, and allows you to interleave things in an interesting way, so I’d say stick with it. I suspect your label graphics could be tarted up somewhat (the present ones have a faint whiff of special-offer stickers in a dodgy supermarket!) but the principle looks great to me.

    I assume you have no objection to us linking to this from oxfordparkinsons.org.uk?

    Thanks again for a fantastic service to the community of interested non-experts.

    Jonathan

    Liked by 2 people

    • Simon

      Hi Jonathan,
      Glad you liked the post – I hope all is well.
      Everything on the website is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), so please feel free to do whatever you like with it. Copy and paste, anything you like.
      And I totally agree about the cheesy labels – I was simply experimenting based on readers requests. I’ll try something else for February. That said, data management is becoming an issue on the site and I am going to have a chat with a local expert on such things shortly.
      Thanks for the feedback – very much appreciated.
      Kind regards,
      Simon

      Like

  2. Lisa Vanderburg (@PDDBSWife)

    Fascinating and funny as always, Simon! I’m fascinated about the Pisa Syndrome – think hubby’s got that (we’d put his spinal twisting down to psoas pull), so I’ll be looking into that – thanks!! Not at all surprised to see rDTMS didn’t do anything useful, unless the subjects’ sprout a major hair-regrowth 🙂

    Like

    • Simon

      Hi Lisa,
      Happy new year – I hope all is well. Glad you liked the post. The Pisa Syndrome study is interesting – it’ll be interesting to see what they do next as a result of their findings.
      Kind regards,
      Simon

      Like

    • GK

      Thank you for such post. It shows that really a lot happening in PD research. It shows that u are really smart guy to put it together( it is also effort to read it )) ), and I am reading your website since I have got PD.It is really important effort u do here. It is good that with time you get more focused on subject. Might be as suggestion you put your personal opinion about potential that particular ideas and novel molecular have to make difference. This post is also shows to me that there is no system in research. Everybody doing randomly and sporadic something, sometimes copy each other wasting time and resources. Sorry for my profanity, but this is how it looks like to me ). BIG THANK U again.

      Like

      • Simon

        Hi GK,
        Thanks for your comment – glad you liked the post.
        Lots of interesting stuff happening in PD research? Yes, and this was just the tip of the iceberg (there were 784 “Parkinson’s” articles published in January 2018 according to Pubmed). This list was solely some of the more interesting bits that I came across.
        Me a really smart guy? Not sure about that. I think the jury is still out on that one.
        I am reluctant to put too much personal opinion into the posts here. I would rather deal with just the peer-review published facts. And ultimately my opinion is irrelevant, particularly in cases where I am discussing areas of research that are beyond my area of expertise. Plus I do not really wish to be held to account 🙂
        Which brings me to your other point regarding the random nature of the research. This is a matter that the general population gets wrong about research (my opinion here). It is such a dynamic environment, shifting and changing on a daily basis based largely on all experimental results coming in and the chance ‘eureka’ observations made by researchers (and now lay people). Along this same line, many folks in the PD community have asked me to provide a map here of the different areas of PD research and what is currently happening, but such a overview would be impossible because it is such ridiculously broad and ever-changing environment.
        I suspect that for February’s review I might try grouping the research into subfields (eg. clinical research, disease modelling, etc), rather than randomly scattering them. Perhaps that might reduce the feeling of ‘sporadic nature’ of the research.
        Many thanks for your thoughts.
        Kind regards,
        Simon

        Like

  3. Kai

    Thank you very much for all the fantastic information. I am not a scientist and although much of the scientific language goes way above my head, I still get a tremendous amount of great information. As a person with PD, its difficult to gather all the different sources of information and read them in a thorough, yet still interesting way as you have. Thanks a million!

    Like

    • Simon

      Hi Kai,
      You are very welcome. Glad you like the website, please let me know if there are any topics you’d like to see discussed.
      Kind regards,
      Simon

      Like

  4. Melanie Powles

    Thank you Simon for the huge amount of time and energy you must be spending on this website. I’m not a scientist but some of this stuff is actually beginning to make some sense to me 🙂 Most particularly, it gives hope … when you see the amount of research coming to light in just one month you can’t help but think more positively. Incidentally, re the item about repositioning drugs … I have been taking estradiol for about a year and recently I’ve been told how well I look ( and in fact I seem to be having fewer ‘off’ times and definitely less low mood and anxiety) Wonder if the hormone treatment is a factor.
    Thanks again
    Mel

    Like

    • Simon

      Hi Melanie,
      Thanks for your kind words about the website – very pleased that you are finding it useful. And thanks for the interesting comment regarding estradiol.
      There is a lot of preclinical data supporting the idea of estradiol having a neuroprotective effect (for example https://www.ncbi.nlm.nih.gov/pubmed/26852701 ), plus individual case studies pop up occasionally ( https://www.ncbi.nlm.nih.gov/pubmed/23627690 ). But there is something critical that we are missing with the estradiol story as different studies have observed very different results (some found it to be beneficial in improving PD severity, while others found it to worsen the condition (this research report provides a good overview: https://jamanetwork.com/journals/jamaneurology/fullarticle/786007 ). And before everyone jumps on this bandwagon, there are side effects to estradiol treatment ( https://www.rxlist.com/estrace-side-effects-drug-center.htm ) so a discussion with ones doctor is required before contemplating any adventurous courses of action. It is intriguing that you are experiencing benefits though. Maybe it could be interesting for you to reach out to one of the research groups and let them know of your experience (your choice entirely of course). Thanks for sharing here though.
      Kind regards,
      Simon

      Like

  5. Kevin McFarthing (@InnovationFixer)

    Hi Simon,

    This is a really good summary, and fully meets your original objective of presenting research progress monthly rather than a massive review at the end of the year. My only suggestion is, as you mention in one of your replies, to group clinical trials, PD biology and new drug targets in separate lists. These summaries will be a great source of information on new therapies to update my spreadsheet – thanks!

    Kevin

    Like

    • Simon

      Hi Kevin,
      I fully agree that grouping the items will make life easier for all (most importantly: me!). Will have another play with the format for the February review.
      Kind regards,
      Simon

      Like

  6. Doug

    Hi Simon
    Thank you so much for this summary. It is so encouraging and hopeful to see the extensive research along many different pathways. Thank you for the site in general. Getting sound scientific information on Parkinson’s in plain English is a great service and is much appreciated.

    Like

    • Simon

      Hi Doug,
      Thanks for your comment. Glad you liked the post. As I said above, this is just the tip of the iceberg, and February is already gearing up to be a huge month for Parkinson’s research.
      Kind regards,
      Simon

      Like

  7. Susan

    This is the blog for which I have been looking! Links to the underlying scientific papers are immeasurably useful. Doctors (including my husband) are not much interested without that data, and since most primary Parkinsons’ disease care is from doctors whose specialty is not limited to PD, I am thankful to have this link to share.

    Like

    • Simon

      Hi Susan,
      Thanks for your comment – glad you like the site. Unfortunately some of the links lead to pay-to-access research publications. Not so useful. But OPEN ACCESS is something else we are working towards.
      Kind regards,
      Simon

      Like

  8. DKDC

    Thanks – I thought it was useful and your ideas to improve it sound good. Like someone else said – I was struck that a lot of work being done to help us folks.

    Like

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