Year in review: 2021

# # # # As with the preceding year, 2021 proved to be challenging due to the continuing COVID-19 pandemic (and it is not over yet). Vaccines were rolled out with remarkable speed, but equally new variants of the virus popped up and have kept Governments and health regulatory bodies on their toes. An amazing feature of the last two years has been the response to the pandemic from the research community – not only in sequencing novel variants and testing new vaccines – but also in terms of keeping research projects ongoing in other fields of science. Despite everything pandemic-related, there has been significant progress in areas like Parkinson’s research. In today’s post, we will consider three big Parkinson’s-related research takeaways of 2021 (based on our humble opinions here at the SoPD), and then we will provide an extended overview of some of the important discoveries and pieces of news from the last 12 months (Be warned: this will be a long post). # # # #

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Source: Thecalculatorsite

There are 52.143 weeks in a year, which equates to:

• 365 sun rises and sunsets
• Approximately 13.3 lunar orbits (Source)
• 8 760 hours
• US$93.86 trillion in global gross domestic production (nominal terms; 194 economies in 2021 – Source)
• 525 600 minutes
• 29.2 tons of adenosine triphosphate (ATP) production and recycling (per person – based on an average 80kg individual)
• 31 622 400 seconds (Source)
• Approximately 35 million heart beats and  8.4 million breaths

Basically, ample time and resources to do some useful stuff (beyond simply binging “Squid games” on Netflix or playing “candy crunch”).

The face of 2021? Source: Tasteofcinema

The last 52.143 weeks have been particularly challenging in many countries due to the ongoing COVID-19 situation. Despite these ongoing challenges, significant progress has been made in the research surrounding Parkinson’s and other neurodegenerative conditions in 2021.

Below we will discuss three of the main research-related pieces of news for Parkinson’s (as determined by the team here at SoPD HQ), before providing a month-by-month overview of the note worthy events.

The main events in Parkinson’s-related research for 2021

(in no particular order)

1. Cell transplantation: The BlueRockers got things started

In June 2021, the stem cell biotech company BlueRock Therapeutics (a subsidiary of the pharma company Bayer) announced that the first participant in their Phase I cell transplantation clinical trial of stem cell-derived dopamine neurons (called MSK-DA01) had been transplanted (Click here to read more about this).

Nine additional participants will be transplanted in the study and they will be evaluated over the following 2 years ( but the announcement proved to be a significant milestone for the field of Parkinson’s research as it represents that first in a large number of new commercial efforts focused on cell replacement therapies for Parkinson’s. Other players in this field include Aspen Neuroscience, Fujifilm/Cellular Dynamics, Novo Nordisk, TreeFrog Therapeutics, Jeil Pharmaceutical, Sumitomo Dainippon Pharma, NurrOn Pharmaceuticals, and BrainXell (there may be others, but these are the ones that come immediately to mind). After decades of slow progress, the next few years may see a rush of stem cell-related cell transplantation activity (Click here to read a SoPD post on this topic).

 

2. Aducanumab: The guardians of the gate

While this is not really Parkinson’s-related, the event could have major implications for future clinical research in the field of neurodegenerative conditions: In June 2021, the US FDA approved Biogen‘s experimental therapy Aducanumab (now Aduhelm) for the treatment of Alzheimer’s because it “is expected that the reduction in amyloid plaque will result in a reduction in clinical decline”. The approval was based on ‘surrogate endpoints’ as opposed to clear evidence of clinical efficiency. The regulator made this controversial move conditional on Biogen having 9 years to conduct Phase 4 ‘post-marketing’ studies to demonstrate actual efficacy (Click here, here and here to read more about this).

In July Biogen mounted a vigorous defense of the reaction to the news, releasing an open letter to the Alzheimer’s community that took aim at critic’s “misinformation” of the approval (Click here to read that letter), while at the same time the company drew criticism with their advertising messaging (Click here to read more about that). At the same time, some patient advocacy groups suggested that the “negative voices” are “not pro-patient” (how is scientific rigor not ‘pro-patient’?!?!? What an idiotic term – Click here to read more about this), and a newly published study revealed that the FDA appears to allow drugs without proven clinical benefit to languish for years on their accelerated pathway scheme (Click here to read more about this).

Uptake of the new drug was very low as insurers and health care providers tired to determine how to fund the $52K per year cost of Aduhelm and awaited input for Government health care providers. In November, the European Medicines Agency’s Committee for Medicinal products for Human Use (CHMP) issued a ‘negative trend vote’ to Biogen regarding any possible approval for ADUHELM/aducanimab (Click here to read more about this), and in December the application was formally rejected, though Biogen has requested a re-examination of the application (Source).

Almost immediately the company announced that they would be reducing the cost of Aduhelm by half (to $28K) and that they would be reducing costs in 2022 to save  in $500 million. In addition, news and speculation of potential buyouts began to flood the grapevine. 2021 was a rollercoaster of a year for Biogen, I am not sure they have steered the ship so well through the stormy seas, but it would be a shame for neurodegenerative research to lose Biogen’s considerable contributions.

The aducanumab situation has highlighted issues with the current drug approval regulatory systems (for example, the US FDA budget is 46% funded by industry – Source), the desperate need of the patient community, the measuring sticks and goal posts used by the research world, and the future potential implications of the US FDA decision – not only complicating the situation for other international health regulatory bodies, but also for the large number of biotech firms who will now want their applications to receive equally lenient terms. It is truly a crazy mess with very real implications for Parkinson’s research (Click here to read a SoPD post on the topic – not a pro-patient statement, but there you go).

 

3. The Joy of smell research

If I was asked which piece of research in 2021 excited me the most, it was the continued publishing of data from the amazing story of the “smell of Parkinson’s”. What started out as an odd question asked at a patient support group meeting several year ago has quickly developed into multiple avenues of new and exciting research. From training dogs to smell Parkinson’s to a better understanding of the shared biology underlying the condition, Joy Milne’s simple inquiry has blossomed into a remarkable body of research that continues to produce new insights and opportunities (Click here to read a SoPD post on this topic).

Joy Milne & the smell of Parkinson’s

This year one of the research reports published by the team Joy is collaborating with presented metabolomics data that revealed lipid dysregulation in Parkinson’s. The research involving analysis on 274 skin swab samples from 80 drug naïve PD, 138 medicated PD & 56 matched control. The investigations used biological pathway enrichment analysis which showed alterations in lipid metabolism related to specific cellular functions (such as the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism, & fatty acid biosynthesis). “This study shows sebum can be used to identify potential biomarkers for Parkinson’s”, but “insufficient clinical data is available for these patients to hypothesise on the ability of a sebum analysis to help stratify disease progression”. I look forward to learning about the next steps in this research (Click here to read more about this report, click here to read the press summary associated with this research, and click here to read a SoPD post on the topic).

 

Those were the three big events & takeaways from 2021 Parkinson’s research for me. It is simply my opinion (which should not carry much weight).

Below is a month-by-month overview of addition interesting pieces of news and research that helped to shape the year that 2021 was in terms of Parkinson’s research, starting with:

January started with a green light for BlueRock Therapeutics (& parent pharma company Bayer) from the US FDA to proceed with Phase I clinical testing to evaluate safety, tolerability & preliminary efficacy of DA01 (stem cell-derived dopaminergic neurons) in Parkinson’s. This will be the “first trial in the United States to study pluripotent stem cell-derived dopaminergic neurons in patients with Parkinson’s” (Click here to read more about this).

The lymphatic system also was in focus in January with a research report indicating that there is a reduction in meningeal lymphatic vessel flow in cases of idiopathic Parkinson’s (compared to controls). The lymphatic system plays an important role in the immune response to injury and aids in the clearance of waste. In mice, the researchers found that the introduction of α-synuclein pathology was followed by delayed brain (meningeal) lymphatic drainage. In addition, the researchers also found that blocking meningeal lymphatic flow in mice treated with preformed alpha synuclein fibrils exacerbated α-synuclein pathology & outcomes (Click here to read the report and click here to read a SoPD post on this topic).

January also saw the publication of encouraging post hoc analyses. The STEADY-PD3 study was a large, multi-year Phase III trial exploring the use of the calcium channel blocker isradipine in individuals recently diagnosed with Parkinson’s. The primary endpoints of the study indicated that the treatment had no effect of the progression of Parkinson’s, but now post-hoc analysis of the STEADY-PD3 data indicates that higher isradipine plasma exposure resulted in decreased cumulative levodopa equivalent dose & extended the period of time between diagnosis and the initiation of anti-Parkinson’s treatment (Click here to read the report and click here to read a SoPD post on the topic).

February was not a good month for Parkinson’s clinical trials (or disclosure of trial results to the patient community). Buried deep inside its annual results, biotech company Biogen announced that the Phase II study of their alpha synuclein immunotherapy BIIB054 (cinpanemab) in Parkinson’s “did not achieve proof-of-concept”. Biogen also stated that it had discontinued development of BIIB054 and will apply learnings to future efforts in Parkinson’s (Click here to read more about this). We are still waiting for publication of the results and learnings of this study (although the dose selection data has been published – click here to read that report).

Then (and you can’t make this stuff up) buried deep inside its annual results, biotech company Sanofi announced “the venglustat Phase 2 trial in Parkinson’s with GBA mutations did not meet the primary endpoint (end-January) & the indication was halted” (Click here to read more about this). The results of Part I of the MOVES-PD study – exploring the safety, pharmacokinetics, and pharmacodynamics of venglustat has recently been published (Click here to read those results), but the Part 2 efficacy results of the study are still awaited.

On a more positive note, an analysis of two large medical databases (the Danish nationwide health registries & the Truven Health Analytics MarketScan) indicated that use of prostate treatments terazosin, doxazosin, and alfuzosin was associated with a 12% to 37% decrease in Parkinson’s (vs use of tamsulosin; n=147,248 pairs – Click here to read more about this and click here to read the associated press release). A clinical trial program exploring the repurposing of terazosin for Parkinson’s is underway in Iowa (USA – click here to read a previous SoPD post about this).

 

On the 25th March, the number of vaccinations administered worldwide against COVID-19 exceeded 500 million – a truly remarkable achievement for modern medicine.

 

In March, researchers also reported that among Accelerating Medicines Partnership Parkinson’s disease (or AMP PD) participants, all of the individuals who carried the Parkinson’s-associated LRRK2 p.R1441G genetic variant (N=89) also carry the more common Parkinson’s-linked LRRK2 p.M1646T variant. In addition, nearly all of the carriers of the LRRK2 p.N2081D variant also carry the LRRK2 rs76904798 variant. This research raised the possibility that having additional variants may have an important cumulative impact on Parkinson’s risk (Click here to read more about this).

 

Another research group presented a wearable patch in March that could continuous analysis of thermoregulatory sweat at rest. How might this be useful for Parkinson’s? It could be an ideal platform to continuously/routinely monitor users’ medical conditions & physiological status during daily routines. Using this technology, the researchers explored sweat levodopa levels in relation to broad beans intake in healthy volunteers. Levodopa concentration in sweat generally increases with increasing doses. Potential for monitoring Levodopa levels in Parkinson’s? The authors wisely cautioned that “the exact relations between sweat levodopa concentration, plasma levels, & intake dose can depend on diet, hydration, other physiological conditions that impact absorption & metabolism rates, & on sweat rate & secretion mechanisms“. They also stated that larger studies are required. Remarkable technology though! (Click here to read more about this).

 

On the 19th April, “117 years after the Wright brothers succeeded in making the first flight on our planet, Nasa’s Ingenuity helicopter has succeeded in performing this amazing feat on another world” – Thomas Zurbuchen, Nasa’s associate administrator for science

April brought with it the publication of lots of ApoE research.

ApoE is a region of DNA that produces a protein (ApoE) that can have different forms – the three most common versions are called ApoE2, ApoE3 & ApoE4. One research report found that APOE4 in particular is associated with faster cognitive decline rate in Parkinson’s, but none of the APOE versions were associated with Parkinson’s related motor progression. Determining a person’s APOE status could potentially be used to predict the cognitive trajectory in Parkinson’s (Click here to read more about this).

Another study published this month provided (Class II) evidence that increased physical activity reduces APOE4-related vulnerability to early cognitive decline in Parkinson’s cohort (N=173 recently diagnosed PD patients; 27% were APOE4 carriers). Larger replication studies are required, but this data is encouraging (Click here to read more about this).

 

Individuals with GBA-associated Parkinson’s have been reported to be more at risk of developing cognitive issues during the course of their condition. Curiously, however, the results of a study published in April suggested that longitudinal cognitive decline in individuals with GBA-associated Parkinson’s is more severe than in those with a combination of two Parkinson’s associated genetic variants – those with GBA-associated PD who also have a LRRK2 variant. The LRRK2/GBA combo was found to more closely resemble the slower progressing LRRK2-associated PD. The biological basis of association/interaction is not clear, but 1193 individuals with Parkinson’s involved in the study (128 (10.7%) had GBA-associated PD, 155 (13.0%) had LRRK2-associated PD, 21 (1.8%) had LRRK2/GBA-combo PD; Remaining 889 (74.5%) had idiopathic PD). “These findings suggest that there was not a convergent deleterious association of LRRK2 & GBA variations in Parkinson’s progression, as would be expected based on prior cellular studies” (Click here to read more about this and click here to read a SoPD post on this topic).

 

In May, technology company SpaceX successfully flew and landed their Starship prototype for the first time:

Researchers also reported in May that long-term wireless streaming of neural recordings from deep brain stimulation devices had been conducted in 5 individuals for up to 15 months. “At home” recordings (made over 2,600 hours) were paired with behavioural data collected from wearable monitors, and this data could be used to identify individual-specific neurophysiological biomarkers during normal daily activities & the researchers used those patterns for adaptive DBS (Click here to read more about this and click here to read an open access preprint manuscript of the study).

The month of May also brought with it a report from researchers at the biotech company Sanofi in which they analysed 87,000 single nuclei collected from the putamen region of the human brain. Samples were collected from healthy controls, Parkinson’s & MSA cases. Oligodendrocytes – a type of helper cell in the brain – displayed distinctive pathological alterations in both PD & MSA cases. Seven subpopulations of oligodendrocytes were identified and curiously, alpha synuclein expression was found to be significantly higher in Parkinson’s oligodendrocytes (vs control as well as in comparison to MSA – click here to read more about this). The researchers also found a possible expansion & activation of microglia & astrocytes in Parkinson’s (vs MSA & controls), as well as altered expression of major neurodegeneration associated genes (SNCA, MAPT, LRRK2, APOE & APP) at cell-type resolution (LRRK2 in OPCs?? – click here to read more about this).

In June 2021, the New Zealand “Black caps” cricket team won the 2019–2021 ICC World Test Championship (Click here to read more about this).

 

There was also some encouraging news in June from the biotech company Anavex Life Sciences which announced that their Sigma1 receptor agonist ANAVEX®2-73 (also known as Blarcamesine) improved both cognitive and motor symptoms in a Phase 2 double-blind, placebo-controlled clinical trial in 132 people with Parkinson’s Disease Dementia. We are now waiting to hear how the company will take this result forward into late stage clinical trials (Click here to read more about this and click here to read a SoPD post on this topic).

 

Also in June, the Edmond J. Safra Foundation awarded £1.4 million to fund the setting up of the Accelerating Clinical Treatments for Parkinson’s Disease project – a Multi-Arm, Multi Stage clinical trial platform to rapidly accelerate the search for disease modifying therapies for Parkinson’s (Click here to read more about this and click here to read a SoPD post about it).

 

And in June, researchers also reported evidence for overabundance of opportunistic pathogens in the Parkinson’s gut microbiota. Short-chain fatty acid (SCFA)-producing bacteria were reduced in PD (Click here to read more about this). Further research from this same group found “evidence that the overabundance of opportunistic pathogens in Parkinson’s gut is influenced by the host genotype at the alpha-synuclein locus, & that the variants responsible modulate alpha-synuclein expression“. They reported that “Genetic susceptibility to disease & the dysbiosis in the gut microbiome are not operating independently“. This research points towards testable hypothesis regarding the incomplete penetrance of Parkinson’s susceptibility genes (Click here to read more about this).

 

In July the biotech firm AC Immune announced the strategic acquisition of AFFiRiS‘s portfolio of therapeutics targeting alpha-synuclein (notably the alpha synuclein-targeting vaccine called PD01). It was an all-stock deal valued at US$58.7M. AC Immune plans to immediately launch an adaptive, biomarker-based Phase 2 study in Parkinson’s. This trial will evaluate a dose-response of the optimized formulation of PD01 (now called ACI-7104) and focus on the immunogenicity against a-synuclein & pathological a-synuclein species. Markers of progression of motor & non-motor symptoms of Parkinson’s will also be monitored (Click here to read more about this and click here to read a SoPD post about this announcement).

In preclinical research published in July, a large drug screening study investigated 230,000 compounds & identified ‘farnesol’ as an inhibitor of “Parkin Interacting Substrate” (or PARIS). It has previously been reported that PARIS levels can accumulate in some cases of PD – increasing due to Parkin inactivation. This increase results in the suppression of a neuroprotective protein called PGC-1α, and leads to dopamine cell loss in models of PD (Click here to read more about this). Screening for PGC-1α inducers, researchers report that farnesol administration inhibits PARIS directly, which stops PARIS from blocking PGC-1α. This leads to an increase in PGC-1α levels, that rescues models of Parkinson’s. Farnesol is a natural molecule produced by plants & mammals. It has anti-oxidant, anti-inflammatory, & neuroprotective properties and has recently been reported to protect a model of multiple sclerosis (Click here to read more about this). It is generally regarded as safe, but it has never been clinically tested in humans. Dosing/safety/tolerability studies will be required before exploring efficacy in Parkinson’s (Click here to read more about the new report, click here to read a press release on the study, and click here to read a SoPD post on this topic)

 

Also in July, two research papers were published back-to-back reporting how the skull & vertebral bone marrow are reservoirs for myeloid cells to the meninges. Myeloid cells are among the most important defenders in our immune system in the fight against infection. The first report finds that in mice replenished myeloid cells in the dura mater are not blood derived rather they transit from cranial bone marrow thru specialized channels; In models of CNS injury & neuroinflammation, they demonstrate that these myeloid cells have an immunoregulatory phenotype compared with their more inflammatory blood-derived counterparts (Click here to read more about this); In the second paper, the researchers reported that the meninges host B cells that are also derived from skull bone marrow, mature locally, & likely acquire a tolerogenic phenotype. They further found that the brains of aging mice are infiltrated by a second population of age-associated B cells, which come from the periphery & may differentiate into autoantibody-secreting plasma cells after encountering CNS antigens. Implications for future treatment of neurological diseases? (Click here to read more about this).

 

 

During the northern Summer month, researchers reported that gut microbiota transplantation from young donors could reverse some aging-associated differences in peripheral & brain immunity (in mice). Bi-weekly fecal microbiota transplants (FMT) for 8 weeks was also found to “attenuate aging-associated deficits in behavior“. At baseline (Pre-FMT), there were clear differences between young & aged mice in the diversity of the gut microbiota. But after 8 weeks of FMT treatment those differences were no longer significant. Exactly how “Young FMT into an aged host may selectively modulate peripheral immunity” is not clear. But in the aged brain, some aspect of the behaviour of resident immune cells – microglial – was reversed by young FMT treatments – click here to read more about this, click here to read the press release and click here to read an SoPD post on this topic).

 

Also in August, the biotech company Clene Nanomedicine reported positive top-line results from its Phase 2 REPAIR clinical trials in Parkinson’s & Multiple Sclerosis. The company’s gold nanocrystal suspension, CNM-Au8, significantly improved brain energetic metabolism based on MRS imaging. 13 Parkinson’s patients were involved in the REPAIR-PD study. NAD+/NADH ratio demonstrated a statistically significant elevation by an average of 0.589 units (10.4%) following 12-weeks of CNM-Au8 treatment (p=0.037). The study also found that CNM-Au8 was safe & well tolerated. The company is now seeking to take their molecule into Phase II testing for Parkinson’s (Click here to read more about this and click here for a previous SoPD post on this technology).

At the start of September, researchers announced the discovery that pharmacological activation of “Smoothened” – a downstream effector of a protein called “sonic hedgehog” – could reduce levodopa-induced dyskinesias in the animal models of Parkinson’s. Dopamine neurons produce sonic hedgehog and release it (along with dopamine) on to target cells in the brain. In Parkinson’s, when the dopamine neurons are lost, we treat the condition with levodopa tablets which replace the lost dopamine, but not the lost sonic hedgehog. The researchers found that the increase in dopamine signaling (via levodopa treatment) + the reduction in sonic signaling = dyskinesias (Click here to read more about this and click here to read a SoPD post on this topic).

 

September also brought the publication of the results of the Phase III SURE-PD clinical trial. This was a randomized, placebo controlled clinical trial of a drug called inosine which has the ability to elevate levels of the antioxidant urate in the body. Individuals with high levels of urate were reported to have a reduced risk of developing PD, and inosine had demonstrated protective properties in models of the condition. So researchers tested inosine on the progression of early Parkinson’s. This was a massive, multi-year study involving 300 participants, but the final analysis concluded that “The findings do not support the use of inosine as a treatment for early PD” (Click here to read more about this).

 

Many people with Parkinson’s have reduced levels of an enzyme called GCase, which is involved in the waste disposal system of cells. Increasing levels of GCase activity have been shown to rescue models of Parkinson’s, so researchers have been searching for activators of GCase as a therapeutic strategy for PD. In October, a new study was published in which the investigators screened 1280 cell-permeable FDA-approved drugs and found that the antipsychotic quetiapine binds to GCase and increases its activity. This activation by quetiapine lowered alpha synuclein accumulation in mice and partially rescued pathology in dopaminergic neurons with LRRK2 mutations (Click here to read more about this and click here to read a SoPD post on this topic).

 

There was also the publication of the results of a small (n=40) randomized, double-blind, placebo-controlled study of a nutritional formula (called Neuroaspis PLP10™, which is made of antioxidant vitamins and omega-3 & omega-6 fatty acids) in early Parkinson’s. The researchers reported significant improvement in ON state UPDRS over the 30 month study – click here to read more about this and click here to read an SoPD post on this topic).

 

In October, there was also the publication of a computational drug-repurposing screening experiment that was seeking to identify molecules that could correct apolipoprotein E4 (APOE4)-related Alzheimer’s phenotypes. It is interesting to see that the study identified the diuretic medication bumetanide. The researchers reported beneficial effects in both in vitro and in vivo models of Alzheimer’s. They also found that drug exposure in human cohorts was associated with a significant reductions in Alzheimer’s prevalence in individuals >65 years (2 databases – click here to read more about this and click here to read a SoPD post on this topic).

 

And finally, in October, researches reported that they may have identified the mystery neurotoxic agent that astrocytes release to kill damaged neurons: Saturated lipids contained in lipoparticles. This form of “Lipoapoptosis” (programmed cell death caused by fatty acids) was demonstrated in both cell culture conditions (Click here to read more about this and click here to read a SoPD post on this topic).

 

In November 2021, the number of research reports on the Pubmed search engine with the keyword “Parkinson’s” climbed over 150,000. It is an impressive number, but it is important to put it into context: Approximately 118,000 (~80%) of those reports have been published since the year 2000, & 75,494 (~50%) since 2012. And the number per year is only accelerating with 11,668 reports published in 2021 alone.

Also in November, the biotech company Yumanity therapeutics announced positive top-line results of Phase 1b clinical trial for YTX-7739 (stearoyl-CoA desaturase inhibitor) in patients with Parkinson’s. The drug was found to be safe & well tolerated over 28 days treatment. “After 28 days of treatment, the 20 mg dose given once-daily reduced the fatty acid desaturation index (FA-DI), a biomarker of stearoyl-CoA desaturase inhibition, by approximately 20%-40%, the range expected to be clinically relevant based on preclinical studies”. The company now plans to advance to Phase 2 (Click here to read more about this and click here to read an old SoPD post on this topic).

November also saw the publication of post hoc re-analysis of the STEADY-PD II clinical trial results that found evidence for slowing the progression of Parkinson’s. The findings suggest that “clinically attainable brain exposure to isradipine may slow early-stage Parkinson’s progression”. “These results are consistent with the recent secondary analysis of the STEADY-PD III clinical trial”. Here is the post hoc analysis of the STEADY-PD III clinical trial. Encouraging as these findings may be, it is important to remember that this analysis is post hoc (after the fact) analysis – which is usually used for hypothesis generation – further carefully controlled clinical trials will be required to determine if isradipine may be having a disease modifying effect in Parkinson’s (Click here to read more about this and click here to read a SoPD post on this topic).

And in early November, a new study was published which found that individuals who started physical activity after receiving their Parkinson’s diagnosis had a lower mortality rate than those who remained physically inactive. The study involved 10,699 individuals with PD and exhibited a dose-responsive association – further evidence for exercising! (Click here to read more about this).

 

In December, the pharmaceutical firm UCB announced that they were partnering up with another pharma company Novartis on Parkinson’s, with development of UCB0599 – a small-molecule alpha synuclein aggregation inhibitor. Alpha synuclein is a protein that accumulates (or aggregates) in certain neurons in Parkinson’s and stopping this aggregation has been viewed as a potential therapeutic approach to slowing/stopping PD. Originally developed by Neuropore Therapies, UCB0599 is currently in Phase II clinical testing. The deal also provides Novartis with an opt-in to develop the immunotherapy UCB7853 (an alpha synuclein antibody – click here to read more about this news and click here to read a SoPD post on this topic).

There was also a research report in December indicating that sleep deprivation increased levels of alpha synuclein protein build up in the brains of genetically engineered mice. The investigators also reported that pharmacologically increasing slow-wave sleep could reduce the alpha synuclein burden. The mechanism of action is not clear (maybe via glymphatic function & modulating protein homeostasis), but the study provides further evidence for the importance of good sleep – which is disrupted in many cases of PD (Click here to read more about this and click here to read a SoPD post on this topic).

 

And the year finished with the publication of the results of a 12-week pilot study exploring the safety and tolerability of the prostate enlargement treatment terazosin in people with Parkinson’s. The results indicated that terazosin has the desired effected of changing ATP levels in the brain & blood, and that it is safe and well tolerated. The team of researchers at the University of Iowa who conducted the study are now exploring the next steps in the clinical testing of terazosin in PD (Click here to read more about this and click here to read a SoPD post on this topic).

 

So what does it all mean?

I don’t know about you, but I am glad to see the back of 2021.

And I look forward to a happier 2022.

Listed above were some of the main events and bits of news for Parkinson’s research in 2021 (according to the humble opinion of yours truly). In the next post, we will look at where things are heading and what is expected in 2022 in our annual “Road ahead” post.

 

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