Welcome to The Top Ten Healthinnovations of 2016, the third-year in our successful series, where the most exciting discoveries and breakthroughs are decided by you, the global medical community. This year heralded an exciting new era for the manual regulation of the human body using neuroscience. After all isn’t this what every drug treatment attains to, the manual regulation of disease or disorder?
Once the health innovator community has solidified this evolution in medicine, humans will truly be limitless with the ability to manually regulate their own bodies, their own disease, and their own neurogenetics. This is being investigated via the brain and neuronal colonies present throughout the body to monitor and regulate its many systems. Studies have identified these neuronal colonies and neuronal-related structures modulating the immune system in the gut and controlling the dilation of blood vessels in the lungs, with recent studies observing the manual regulation of disease and immunity. The brain regulates our body utilizing gene-encoded neurons in constant epigenetic cascade, it is hoped this cascade can be harnessed to control a multitude of processes.
The era of medicalized neuropsychiatry is also upon us leading to intricate maps of neural networks, neuroimaging mental disorders on a single-cell level, a direct result of nanotechnology, and precision medicine. These studies hone in on the nanoscale, genetic and epigenetic-gated neurons to the very single dendrite, as well as the minutest synaptic valley.
This year also saw not just one, but two human studies for the elusive Alzheimer’s disease blood test, giving the luxury of multiple biomarkers in the blood at the earliest possible stages of this debilitating disease. This has in no means stopped the neuroimaging juggernaut, the one true non-invasive neurologically-based biomarker, now crucial for validation at every step of neuroscience-based trials and disease diagnostics. Some amazing systems are now being imaged in the brain bringing the world of medicine closer than ever to whole-body regulation and controlling the epigenetic cascade. Affected by the environment, these neural epigenetic systems decide on the disease and disorder fate, possibly leading to the inception of post-natal genetic design and out-of-the-womb designer babies.
So here we go health innovators, the strongest studies for the year.
At number one, the top global Healthinnovations for 2016 is from Ruhr-Universität Bochum. This pièce de résistance pushes forward whole-body manual regulation via neuronal colonies and neuronally-related structures with the discovery of olfactory receptors in human bronchi. The researchers discovered two types of olfactory receptors in the human muscle cells of bronchi, and state if these receptors are activated by binding an odorant, causing them to dilate and contract, they could be a new and exciting approach for asthma therapy.
Originally, olfactory sensory neurons in the nose were thought to exclusively express olfactory receptors. However, emerging data demonstrate olfactory receptors aren’t restricted to the nose and can be found in various human tissues. In the last decade, olfactory receptors have been shown to regulate essential physiological functions, such as the regeneration of keratinocytes, sperm motility, and even the inhibition of prostate cancer and hepatocarcinoma cell proliferation.
The current study shows olfactory receptors are expressed at the mRNA and protein levels in human airway smooth muscle cells. This study not only mapped the human olfactory receptors, OR1D2 and OR2AG1, but it also went on to regulate bronchiole contraction at a single-cell level via the newly mapped olfactory receptors.
These amazing findings provide the first evidence human olfactory receptors are functionally expressed in human airway smooth muscle cells and regulate pathophysiological processes. The study also changes the whole landscape by providing new therapeutic targets for early-stage chronic inflammatory lung diseases via neuronal colonies and their related structures throughout the body.
The second most successful study of the year from Massachusetts General Hospital imaged whole-brain epigenetics. This magnum opus provided images of epigenetic activity within the human brain for the first time and a way of understanding interactions between genes and the environment in the brain via neuroimaging.
Epigenetic dysfunction is implicated in many neurological and psychiatric diseases, including Alzheimer’s disease and schizophrenia. Therefore, histone deacetylases (HDACs), important regulators of gene transcription, are being aggressively pursued as therapeutic targets. The researchers used Martinostat to quantify HDAC expression in the living human brain with results showing HDAC expression was almost twice as high in gray matter as in white matter. Notably, within gray matter structures, uptake was highest in the hippocampus and amygdala, whilst being lowest in the putamen and cerebellum.
HDAC deregulation has been implicated in a growing number of brain diseases, so being able to study gene transcription regulation both in the normal brain and through the progression of disease should help the global medical community better understand disease processes and why they manifest. This could also allow the global medical community to investigate why some people genetically predisposed to a disease are protected from it, and why events during early life or adolescence have such a lasting impact on brain health.
In at number three is Rowan University with a blood test which leverages the body’s own immune response to detect an early stage of Alzheimer’s disease in a human study. Their test demonstrated an overall accuracy, sensitivity, and specificity rate of 100 percent in identifying subjects whose mild cognitive impairment was actually caused by an early stage of Alzheimer’s disease.
The study analyzed blood samples from 236 subjects, including fifty mild cognitive impairment subjects with low levels of amyloid-beta peptide in their cerebrospinal fluid. The lab also identified the top 50 autoantibody biomarkers capable of detecting ongoing early-stage Alzheimer’s pathology in patients with mild cognitive impairment. Results show in multiple tests, the fifty biomarkers were 100 percent accurate in distinguishing patients with mild cognitive impairment due to Alzheimer’s from healthy aged and gender-matched controls.
As this blood-based diagnostic strategy is dependent on the presence of Alzheimer’s pathology known to be underway many years before symptoms emerge, this approach could open the door to even earlier pre-symptomatic detection of Alzheimer’s disease. These results show it is possible to use a small number of blood-borne autoantibodies to accurately diagnose early-stage Alzheimer’s disease, and could eventually lead to the development of a minimally-invasive way to diagnose this devastating disease in its earliest stages.
It was a shock in 2014 when researchers found that exercise caused animals to forget learned-based knowledge, a finding the next study at number four from the Texas A&M College of Medicine repudiates. Their study showed exercise causes more new neurons to be formed in the hippocampus, and contrary to the earlier study, these new neurons do not cause the individual to forget old memories.
The team actually replicated the 2014 research, using rats instead of mice, as rats are thought to be more like humans physiologically with more-similar neuronal workings. Their results showed the rats who ran further over the course of a set time had much greater neurogenesis in their hippocampus, and all rats who had access to a wheel had greater neurogenesis than the sedentary group. Data findings show on average, the rats ran about 48 miles in four weeks, with neuron formation doubling in the hippocampus of these animals.
Taken together these results suggest exercise greatly increases neurogenesis in the hippocampus, which has functional implications. As neurogenesis is important for maintaining normal mood function, as well as for learning and creating new memories, importantly this connection may help explain why exercise is an effective antidepressant.
At the midway mark is Rockefeller University with another great inroad for manually regulating the human body via neuronal colonies. This amazing development showed neurons play a role in protecting intestinal tissue from over-inflammation, with implications in the treatment of gastrointestinal diseases such as irritable bowel syndrome.
Intestinal tissue is continuously exposed to numerous microbe-and food-derived antigens, with different populations of macrophages among the many types of immune cells present in this tissue providing protection from these antigens. The current study identifies a mechanism by which neurons work with these immune cells to help intestinal tissue respond to perturbations without going too far.
Specifically, it was shown muscularis macrophages carry receptors on their surface allowing them to respond to norepinephrine, a signaling substance produced by neurons. The presence of this receptor might indicate a mechanism neurons use to signal immune cells to dampen inflammation and suggests one of the main signals which may induce a different response to infection appears to come from neurons encircled by the muscularis macrophages. Importantly, it was observed that the muscularis macrophages are activated by neurons within one to two hours following an infection, significantly faster than a response would take if it were completely immunological.
With this, the global medical community now has a much better picture of how the communication between neurons and macrophages in the intestine helps to prevent potential damage from inflammation.
Number six on this great list is SUNY Downstate Medical Center with a masterclass in precision single-cell biology. This study goes down to the nanometer to identify the brain receptor responsible for initiating the adolescent synaptic pruning which goes awry in both autism and schizophrenia.
During puberty the density of dendritic spines decreases by half in widespread areas across the CNS, this includes the CA1 hippocampus and temporal lobe, sites essential for learning and memory. The researchers identified the single-cell starting point of adolescent pruning, which requires GABARs and affects cognition. The study showed the GABA receptors trigger synaptic pruning at puberty in the mouse hippocampus and reduce brain activity to decrease levels of a protein in the dendritic spine, known as kalirin-7, shown to stabilize the scaffolding in the spine to maintain its structure. The mice that did not have these GABA receptors didn’t undergo synaptic pruning and maintained the same high-level of brain connections throughout adolescence.
However, the mice whose brains consist of too many brain connections, are able to learn spatial locations but are unable to re-learn new locations after this initial retention of knowledge, suggesting too many brain connections may limit learning potential. These findings are highly salient for children with autism who have been shown to have an over-abundance of synapses in some parts of the brain.
Other research indicates prefrontal brain areas in people with schizophrenia have fewer neural connections than normal, suggesting new treatments targeting GABA receptors for normalizing synaptic pruning in diseases such as autism and schizophrenia could work.
Number seven on our list is from Lund University, whose sets of studies work towards generating consistent good manufacturing practices (GMP) for human-pluripotent stem cell-derived neural-progenitors, so they will mature and function correctly in the adult brain after transplantation. Using the newly identified markers for standardization the researchers were able to develop a GMP-differentiation protocol for highly efficient and reproducible production of transplantable dopamine progenitors from human pluripotent stem cells.
They did this by successfully identifying a specific set of markers correlating with high dopaminergic yield and graft function after transplantation in animal models of Parkinson’s disease. Guided by this information, these studies developed a better and more accurate method for producing dopamine cells for clinical use in a reproducible way.
At number eight in the world’s top Healthinnovations for 2016 is the University of Tsukuba and the University of Tokyo concentrating on precision single-cell neurobiology. This advancement clarifies the mechanism in the brain preventing derailment of the receptor transportation system that supports memory.
In order for memories to be created inside the brain, NMDA glutamate receptors must first be transported to the synapses. The team shows a molecule known as the microtubule-associated protein 1A (MAP1A), connects NMDA glutamate receptors to microtubules as they are being transported to the synapses. This was shown to stabilize the receptors, preventing them from becoming derailed, as well as playing a crucial role in improving the overall efficiency and stability of the transportation process.
This study indicates MAP1A plays an essential role in maintaining synaptic plasticity in mice; with animals lacking this protein exhibiting learning disabilities, and reduced synaptic plasticity attributable to disruptions of the anchoring machinery. This is because, in the nerve cells of mice lacking MAP1A, the NMDA glutamate receptors are not carried effectively to the synapses, resulting in a remarkable loss of memory-based capability.
The development of drug and gene therapies capable of acting on the receptor transport support system clarified in this study is expected to give rise to new treatment strategies for memory impairment and schizophrenia.
At number nine is George Washington University with a new method to map and track the function of brain circuitry affected by Autism spectrum disorder (ASD) in boys using neuroimaging. Their technique is expected to provide clinicians and therapists with a physical measure of the progress patients are making with behavioral and drug treatments, a tool that has proved elusive in autism treatment until this point.
ASD is characterized by impairments in social communication as well as restrictive, repetitive behaviors, and while behavioral symptoms are well-documented, investigations into the neurobiological underpinnings of ASD have not resulted in firm biomarkers. This research involved analyzing a series of 164 images from each of the 114 study participants to show the brain scans of the social perception circuits only indicated ASD in boys, not girls. The team successfully showed non-invasive, tangible brain scan data can be an effective indicator for the function of the social perception circuits in patients and has the potential to improve treatment for ASD by measuring changes in the social perception brain circuit in response to different interventions.
At number ten are Tel Aviv University and Harvard University with a human study validating the second Alzheimer’s disease blood test in your list of innovation. This study proposes a new biomarker for cognitive aging and Alzheimer’s disease, namely, activity-dependent neuroprotective protein (ADNP), the levels of which can easily be monitored in routine blood tests.
ADNP is associated with cross-communication among neural nerve cells and their support cells, it was shown the more ADNP-RNA found in the blood, the fewer aggregates were found in the brain of elderly individuals. The team states this indicates a clear connection between ADNP-levels in the blood and amyloid plaques in the brain.
The study went on to analyze blood samples taken from 42 healthy adults, mild cognitive impairment (MCI) patients, and Alzheimer’s disease patients, later validated by an independent study. Significant increases in ADNP-RNA levels were observed in patients ranging from MCI to Alzheimer’s dementia, with ADNP levels tested in the blood also correlating with higher IQ in healthy older adults. ADNP-levels tested in plasma and serum samples, as well as white-blood-cell RNA levels, distinguished between cognitively normal elderly, MCI, and Alzheimer’s dementia participants, indicating a clear connection between ADNP-levels in the blood and amyloid plaques in the brain; holding the potential to provide the basis of non-invasive blood tests.
Congratulations to everyone who made the list, it’s a great achievement. See you all in 2017!
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