Following last year’s whirlwind of headlines on aducanumab, this year has seen the drug enter our top highlights again. However, this year it wasn’t a question about what happened or why, but instead, whether or not the US FDA would approve the drug for Alzheimer’s disease. Our heads were turned in November when Biogen’s and Eisai’s stocks both jumped 40% after the FDA seemingly indicated that aducanumab was sufficiently safe and effective. This then took a quick turn when their advisory committee voted against the approval of the drug, as they determined that evidence from a single study was not sufficient to demonstrate efficacy.
Researchers have edged closer to success this year with the development of a blood test for Alzheimer’s disease. But rather than focusing on amyloid-β, a lot of attention was geared towards p-tau variants. For example, one of the first studies we covered reported on the diagnostic value of p-tau181 and how it was a stronger predictor of developing Alzheimer’s in healthy elders than amyloid. We then heard about multiple studies presented at AAIC 2020 indicating that blood p-tau217 demonstrates high accuracy as a biomarker for Alzheimer’s disease, even more so than p-tau181.
When the COVID-19 pandemic first started, there was little to no information about how it would impact the field of neurological diseases. Given the shift to home working and the isolation measures put in place, one thing was for certain though – the pandemic was (and still is) having an impact on mental health. Our article on COVID-19 and mental health, including what we can all do to help, proved to be extremely popular. As more information about the virus was gathered, we heard how exposed individuals may be at a heightened risk of neuropsychiatric symptoms and the impact that stress from the pandemic has had on the brain.
Another popular story we saw, which also relates to COVID-19, included an article on how delirium, brain inflammation, stroke and nerve damage might possibly be neurological complications of the disease, even in the absence of severe respiratory symptoms. In another popular news highlight, a meta-analysis involving 24 studies, which was published in JAMA Neurology, highlighted that delirium may be associated with long-term cognitive decline. The researchers determined that a person who experiences an episode of delirium could be more than twice as likely to show significant long-term cognitive decline.
Bringing the spotlight to epilepsy, one of our biggest features included a video from our sister site, the Video Journal of Biomedicine, on the current status of drug development in the field. Here we heard from Ana Mingorance (Loulou Foundation, London, UK) on how the landscape of the field has changed, what new technology developments have been made and the challenges surrounding regulatory approval of new drugs for epilepsy. In addition to this, a study published in Nature Communications discovered that a novel mechanism for synaptic plasticity could have pharmacological applications in the treatment of epilepsy.
Functional cognitive disorder
This year has seen a big focus on mild cognitive impairment (MCI), as the phrase is used to define individuals who have a wide range of underlying causes. Given that not all people with MCI will go on to develop dementia, and not all cases of MCI are due to neurodegenerative processes, it’s crucial to be able to distinguish between them. One study earlier in the year reported that up to one-third of individuals who go to a specialist memory clinic may have ‘functional cognitive disorder’, a condition that could be commonly mistaken for early dementia or MCI.
Over the last few years, we have seen a growing interest surrounding the gut–brain axis and the role of the microbiota. As such, we put together a written panel discussion on this to explore how far our understanding of the gut–brain axis has come, what therapeutic approaches are emerging from this research and what types of studies are required to fill our current gaps in knowledge within the field. Another highlight on this topic included a news story on how Bacillus subtilis – a probiotic bacteria – can prevent the accumulation of α-synuclein in a Caenorhabditis elegans model of Parkinson’s disease.
Another hot topic revolved around traumatic brain injuries. A few months ago, a team of researchers developed a method for detecting traumatic brain injury ‘on the spot’ by examining biomarkers that are released immediately after a brain injury happens. The results showed that biomarker levels were around five-times higher in the traumatic brain injury group compared with controls. Moreover, we featured an interesting editorial on the complexities of traumatic brain injury following domestic violence, which includes insights into the ensuing brain pathology and the long-term emotional and cognitive difficulties that victims may face.
A lot of traffic this year has been directed towards our In Focus features, where we put two particular topics into the spotlight: multiple sclerosis and COVID-19. One particular feature that we saw rise up our charts included a piece on how the COVID-19 pandemic has affected research labs across the globe. Not only have researchers had to adapt to a life of working from home, but most have found themselves unable to carry out their experiments, depending on the type of data collection they needed.
Quite a few news stories have emerged this year regarding neurological diseases or aspects in children. First, we heard how a team in the USA used machine-learning techniques to identify personalized brain networks in children. Second, researchers reported that a combination of stem cell therapy and educational intervention could significantly help children with autism spectrum disorder. Last, we took a look behind the scenes of a research paper on sleep–wake disturbances after acquired brain injury in children who had survived critical care, which highlighted the importance of screening for sleep disturbances after brain injury.
Our highlights for this letter revolve around sKin. First up, a team of scientists created a simple skin test that may be able to accurately identify Parkinson’s disease. The test involves using a chemical assay that can detect clumping of α-synuclein in skin samples. However, next up is where it goes into a bit of a grey area regarding this topic. Not too long ago, researchers developed artificial skin that can electronically replicate the way human skin senses pain. The device is capable of replicating the body’s response to painful sensations with the same speed at which nerve signals travel to the brain.
In the field of Alzheimer’s, the value of lithium therapy has been controversial as studies have used different approaches, treatment doses and study conditions. However, one study at the beginning of the year reported on how lithium could halt signs of advanced Alzheimer’s pathology in rats and recover lost cognitive abilities when given in doses of up to 400-times lower than what is currently being prescribed for mood disorders. The investigators noted that while it’s unlikely that any medication will reverse the brain damage from Alzheimer’s, it’s possible that treatment containing microdoses of lithium could have tangible benefits.
During the first UK lockdown, we explored how the COVID-19 pandemic was impacting various groups of people, particularly in the field of multiple sclerosis. During this time, we heard perspectives from both a clinician and someone living with multiple sclerosis. From a clinical point of view, Gavin Giovannoni (Barts, London, UK) spoke about the shift to telemedicine consultation, managing treatments, vaccine implications and more. From a patient perspective, Trishna Bharadia described the importance of self-management, the need for alternative healthcare solutions and what the new ‘normal’ encompasses.
Back in 2018, researchers reported a breakthrough in using neurotechnology to restore walking in individuals who were paralyzed as a result of spinal cord injuries. We had the pleasure of catching up with the corresponding author of that study to hear more about what further work has been done since then, including how close we might be to translating this rehabilitation paradigm into a clinical setting. In the field of traumatic brain injury, we explored the challenges surrounding the implementation of neurotechnology and artificial intelligence in a healthcare setting, including the ethical implications surrounding this.
Another topic that was popular on our website revolved around a study from scientists in Japan who investigated the effects of oxytocin on the amyloid-β-induced impairment of synaptic plasticity in mice. According to the team, this is the first study to demonstrate that oxytocin can reverse Aβ-induced impairments in the mouse hippocampus. They cautioned that further in vivo research needs to be conducted before oxytocin can be targeted as a drug for Alzheimer’s disease. Although these are only the first steps, this opens a window into an interesting possibility for oxytocin to be used as a therapeutic modality for Alzheimer’s.
Although the field of neurology is still in the early stages when it comes to precision medicine, it’s still proved to be a topic of very high interest to our audience members. We wanted to explore this topic in more detail by featuring an ‘Ask the Experts’ discussion with two key thought leaders in the field. In this feature, we explored what progress has been made with regards to precision medicine and neurological diseases, what promising avenues are being developed, challenges surrounding implementation, main barriers hindering progress, the value of artificial intelligence and what advancements are required to move the field forward.
Next up from our top content we have a news story about how researchers have identified a comprehensive ‘atlas’ of the toxic immune cells that are able to damage the brain. This study used a technique termed ‘Tox-seq’ to develop the molecular profile, which was reported to be successful in the identification of a possible new drug target for multiple sclerosis. Within their studies, which were conducted in mice, the investigators stated that “coagulation and oxidative stress are at work in the same immune cells in the brain.” They then used high-throughput screening to identify compounds that could combat the oxidative stress.
This year we were delighted to feature an editorial from our regular contributor, Dani Beck, about the lingering misconception that academia is unaffected by racism and the impact of systemic racism. Dani explained to us how science and academia are not disjointed from issues of racism and that, in fact, they are partners in crime, as science was at the forefront of the invention of race. He also provides us with a brief history of academia’s involvement in racism and race science, in addition to describing his personal experience with racism in academia. If you haven’t already caught up with this piece, then we highly recommend that you do!
Stem cell therapies
Taking a leap into the spotlight, we saw two interviews that we published in the field of stem cell therapies top our charts. In the first instance, we looked at what significant breakthroughs have been seen in the field of Parkinson’s disease, in addition to the current limitations that stem cell therapies have in the field. In the second instance, we explored the field of neurological diseases as a whole and questioned whether stem cell therapies on their own would be a viable treatment option, or whether a combination approach involving disease-modifying therapies would work best.
This year we saw a really interesting news story about how researchers have identified biological markers present in childhood that relate to amyotrophic lateral sclerosis (ALS) These markers, which are present in teeth, were identified by using lasers to map growth rings that form daily in teeth. From these growth rings the researchers discovered evidence from birth and within the first 10 years of life, which implicated that individuals with amyotrophic lateral sclerosis metabolized metals differently compared with individuals without the disease. This dysregulation in metal uptake was also observed in teeth from a mouse model of ALS.
Putting a punny twist on things, we came across a popular news story this year on ursolic acid – a compound that is found in the peels of fruits – and how it could be an a-peeling approach for the treatment of multiple sclerosis. The compound was reported to prevent further damage to neurons in mouse models of multiple sclerosis and was described to spur neuronal repair by helping to rebuild the myelin sheath surrounding neurons. As these results are only preliminary, a number of tests need to be carried out before the first clinical trials can go through. But the team hope to test the compound further for safety, as it may be toxic at high doses.
The discovery of a new and rare form of dementia, which researchers have termed vacuolar tauopathy, became big news towards the end of the year. When examining brain tissue obtained from a deceased donor who had an unknown neurodegenerative disease, the team were able to identify a novel mutation in the VCPgene in the brain. In addition to this, they also observed a build-up of tau proteins and neuronal vacuoles located in the regions of the brain that were degenerating. This exciting discovery shines a light on a pathway that could lead to protein build-up in the brain, which may be used as a target for new therapies.
World Mental Health Day
Making it into our A–Z round-up again this year, our content around mental health sparked a lot of interest. One particular piece proved to be extremely popular as our regular contributor, Dani Beck, spoke about the facts, figures and flaws of academia in relation to mental health. Due to the popularity of the piece, we decided to team up with our sister site, BioTechniques, to co-host a Twitter chat on mental health in academia(#TalkMentalHealthSTEM), which Dani was also involved in. Here, our fantastic array of panelists discussed questions ranging from the pressures that PhD students face, to the impact that COVID-19 has had on mental health.
Looking at the field of neuro-oncology, another one of our highlights included a news story on a precision medicine approach used to identify new therapeutic candidates for medulloblastoma. The investigators screened medulloblastoma tumors from patient-derived xenografts (PDX) against a drug library to identify a particular candidate that could extend the survival of mice harboring the corresponding PDX model. Additionally, we looked behind the scenes of an article on safety considerations for nanoparticle gene delivery in pediatric brain tumors.
A popular topic that has carried over from 2019 includes early detection of neurological diseases. In this instance, researchers discovered subcellular signs of young-onset Parkinson’s disease that emerge before symptoms arise. The team obtained blood cells from people with young-onset Parkinson’s disease and used them to generate pluripotent stem cells, which were subsequently used to produce dopamine neurons. Within their cultures, the investigators noticed malfunctions in lysosomes and accumulation of α-synuclein, which are the very first signs of young-onset Parkinson’s.
One news piece that we featured earlier in the year attracted a lot of attention, as it was announced that Zolgensma® received conditional approval by the European Commission to treat patients with spinal muscular atrophy. This intravenous gene therapy works by delivering a new working copy of the SMN1 gene into a person’s cells, subsequently halting disease progression. This approval marks an important step forward in the field, as key milestones were met that had never been achieved before in untreated spinal muscular atrophy Type 1 patients. For example, patients were able to sit without support, crawl and walk independently.
With all the great research 2020 has seen, we’re looking forward to seeing what exciting new discoveries 2021 will hold for neuroscience and neurology!