Authors: Sharon Salt, Editor
Could alcohol abuse be the most significant risk factor for dementia? Out of 57,000 cases of early-onset dementia, it was discovered in the largest study of its kind that 57% were related to heavy alcohol consumption. Although the study does not suggest that moderate alcohol intake could cause early-onset dementia, it does imply that the role of alcohol in the development of dementia be given more consideration during diagnosis.
Four researchers were jointly awarded the prestigious Lundbeck Foundation Brain Prize in recognition of their contributions to our understanding of Alzheimer’s disease (AD). Between them they have researched genetic factors underlying AD, the role of secretases in AD, and the make-up of neurofibrillary tangles. Their significant findings now represent some of the greatest advances in our understanding of this difficult disease.
With a long list of environmental risk factors being reported for dementia, could caffeine be added to the list? It has been suggested that coffee, or caffeine, may be a prophylaxis for dementia in both individuals with Alzheimer’s and in the normal aging process. But conversely, scientists have suggested that long-term consumption of caffeine may actually lead to negative effects for people with AD, with the potential to worsen neuropsychiatric symptoms.
A new link between diminished input from dopamine-firing cells deep inside the brain and the ability to form new memories could be crucial in detecting the earliest signs of AD. Investigators have revealed a key link between the size of function of the ventral tegmental area, the size of the hippocampus and the ability to learn new material. Although more studies are necessary, these findings could lead to a new way of screening for early signs of disease.
On Purple Day (26 March), we delved into what can be seen as a controversial area: the use of cannabis-derived therapeutics for the treatment of epilepsy, including current consensus, controversies and future outlook. This year, we’ve also seen positive results in a number of studies investigating cannabidiol. For example, Epidiolex® was the first US FDA-approved cannabinoid-derived drug for seizures, suggesting that these products could become more commonplace.
Unfortunately, 2018 has seen more than its fair share of Alzheimer’s drug trials failing their clinical endpoints. For example, HTL0018318 was halted following an unexpected result in a toxic reaction from an animal study involving a non-human primate. Additionally, azeliragon failed its Phase III clinical trial by not meeting its co-primary efficacy endpoints. However, researchers discovered a vicious feedback loop underlying brain degeneration in AD, which may explain why so many drug trials in the field might have failed.
The gut microbiome and its role in neurological disorders is an up-and-coming area of research with numerous advances across the field this year. For example, proinflammatory bacteria have been reported to be present in the gut in people with AD. Additionally, microbiome research on monozygotic twins has indicated that multiple sclerosis (MS) characteristics could be transferred via fecal transplantation. The risk of developing autism has also been linked to maternal microbiome health.
The publication of a paper in Nature earlier this year described a new platform to study hippocampal-dependent spatial navigation: the Honeycomb maze. Designed to overcome challenges presented by current tests, the maze has been in development for over a decade while different technologies and configurations were tested. We had the opportunity to find out more about the maze, including how it’s being put to use across the spectrum of neuroscience research.
This year has also seen the introduction of our new series of reports focusing on industry news across the field. Among the 2018 headlines were reports that spinal muscular atrophy has seen olesoxime discontinued after “many difficulties” during development, but there have been a flow of successes for Aimovig® for the prevention of migraine – from gaining US FDA approval and receiving a positive CHMP opinion, to receiving an EMA license; making it the first and only treatment approved in the EU and Switzerland.
Did you know that registered members of Neuro Central have free access to all five of Future Medicine’s neurology and neuroscience journals, all of which are peer-reviewed? You can also view our editorial highlights from these journals directly on the website by clicking the journal covers here. Our picks include a research article from Neurodegenerative Disease Management on how age and disease duration affect Parkinson’s treatment outcome with levodopa–carbidopa intestinal gel.
A nasal spray formulation of ketamine held promise this year in the rapid treatment of symptoms for major depression and suicidal thoughts. Upon comparing the efficacy of standard treatment plus intranasal esketamine or placebo, a significant improvement in depression scores and decreased suicidal ideation were reported in the esketamine group compared with placebo. Nonetheless, additional research is required into the abuse potential of the drug.
Preclinical results have indicated that LMTM, the active agent in the LMTX® drug originally developed for AD treatment, may also be beneficial as a Parkinson’s disease (PD) medication. The protein aggregation inhibitor was reported to decrease α-synuclein inclusion in a transgenic mouse model of synucleinopathy. As synucleinopathies are common to multiple neurodegenerative disorders, the findings may herald further research into novel treatments.
A study in Lancet Neurology dominated the headlines in October when a new MS subtype was identified: myelocortical MS. We went behind the scenes to ask lead investigator Bruce Trapp (Cleveland Clinic, OH, USA) how his team identified this subtype, what challenges are yet to be overcome, and what further investigations they have planned to unravel the molecular mechanisms behind their observations.
The National Institute for Health and Care Excellence (NICE) has made the headlines a few times this year with their recommendations against major drugs Ocrevus® (ocrelizumab) for MS and Spinraza® (nusinersen) for spinal muscular atrophy. In both instances, the cost–effectiveness of the drugs was deemed too high. Although Roche (Basel, Switzerland) offered a lower price for ocrelizumab, NICE were unable to accept a different price to that which they already pay for it to treat relapsing MS.
2018 has seen a whirlwind of events with regards to ocrelizumab as a treatment option for MS. In January, ocrelizumab had been licensed to treat patients with both relapsing and early primary progressive MS by the EMA. Subsequently, after a reversal of an earlier decision, NICE announced that they approved the drug for relapsing–remitting MS but also announced they were not going to make the treatment available for primary progressive MS.
The use of cell and gene therapy for PD has seen an array of advancements this year, starting with promising 6-month results reported for the first-in-human clinical study of neural stem cells in people with Parkinson’s. An investigational gene therapy (AXO-Lenti-PX) for PD was also licensed earlier in the year, and another gene therapy has been indicated to slow the progression of neuronal loss in a mouse model of the disease.
At the beginning of the year, the field saw an onslaught of terminations for Alzheimer’s research programs, with big pharma companies Merck & Co. (NJ, USA), Boehringer Ingelheim (Rhein, Germany), Eli Lilly (IN, USA) and Pfizer (NY, USA) announcing a series of failures and terminations of their AD trials and research programs.
One question that still evades neuroscientists is how exactly our human brains differ from those of other animals. This mystery is yet to be resolved, but the discovery of a new cell type termed the rosehip neuron – which may only be present in humans – could one day unlock the mystery of what makes us so different. Although this hasn’t been 100% confirmed, this demonstrates the potential drawback of using lab mice to model human neurological diseases.
Stem cell therapies are an extremely interesting area of research, particularly in the field of MS, where an international trial deemed HSCT safe and effective as a treatment option for people with relapsing MS. As considerations into their use for treatment can be a cause for debate, we opened the discussion to a panel of experts who spoke more about the HSCT trial, including how adult stem cells fare in relation to other stem cell options.
Over the last year, two studies have indicated a relationship between TBI and dementia. The first study implied that TBI increases the risk of dementia for more than 30 years after the injury, with the second reporting that a single TBI characterized as ‘severe’ increased dementia risk by 35% and ‘mild’ by 17%. Questions were also raised as to whether circulating biomarkers could help with prognostication, and if brain cooling was beneficial for TBI patients.
UK Dementia Research Institute (UK DRI)
Throughout this year, we had the brilliant opportunity of catching up with some of the faces from the UK DRI, one of the newest partners for Neuro Central. We heard more about the challenges and opportunities in the dementia care research field from Adrian Ivinson, COO. In addition, we also spoke with Giovanna Mallucci about translating innovation from lab to clinic, and Tara Spires-Jones on her work into the roles of ApoE4 and clusterin in synapse degeneration in Alzheimer’s.
In the field of glioblastoma, we’ve seen an array of potential vaccine candidates emerge this year, such as a Zika glioblastoma vaccine and an immunotherapy (DCVax®-L) for newly diagnosed glioblastoma. Addition of DCVax-L to standard therapy was reported to be feasible and safe in patients, and may improve survival. More recently in the Alzheimer’s field, news of a DNA vaccine also reported decreased build-up of beta-amyloid and tau in the brains of mice.
Women in science
In March we were proud to feature an interview with Samantha Yammine (University of Toronto, Canada) as part of the #PressforProgress campaign on International Women’s Day. Samantha spoke to us about her work, but also the hurdles she’s experienced as a female early-career researcher in STEM. Take a look at how we celebrated more fantastic women in STEM here. Additionally, we put together a feature on neuroscience nurses that highlights more remarkable women in the field.
It has been known for some time that sex-specific differences are present in multiple neurological cases (e.g., autism and glioblastoma). This year, we saw further evidence to support this claim, as researchers reported sex-specific differences to be present in microglia in mice. For example, male microglia seem to contain more proteins responsible for stimulating T cells during inflammation and female microglia contain more active genes for DNA repair.
In late 2017, we launched our Early Careers Zone to provide early-career researchers (ECRs) with a platform for expert insights, career advice and the opportunity to feature their work on the site. In 2018, we’ve enjoyed having ECRs share their insights from conferences such as ARUK 2018 and FENS 2018. We also had the pleasure of interviewing ECRs about their work, including research on pediatric development, opioid abuse and tissue clearing techniques.
The Zika virus is renowned in neuroscience for being an underlying cause of microcephaly, but who would’ve thought we could turn the ‘bad’ side of this virus into a virotherapeutic for glioblastoma? Not that long ago, a team of researchers demonstrated that a live, attenuated version of Zika could form the basis of a new treatment option for this fatal brain cancer. Although a ready-to-use Zika glioblastoma vaccine may not be imminent, early results have certainly been promising.