The Top Ten Healthinnovations of 2016.
Welcome to The Top Ten Healthinnovations of 2016, the third-year in the successful series! Where the most exciting discoveries, verification, validation and breakthroughs are decided by you, the global medical community. What started off as a quiet year, on reflection was the very slow and quiet start of something so monumental, so astounding it promises to change the very landscape, the very targets, the very way humans view their own bodies and its treatments, namely, using the neuroscience of the brain to manually regulate the human body. After all isn’t this what every drug treatment attains to, the manual regulation of the manifestation and/or severity of disease and disorder?
Once the global medical community has solidified this new era of 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 precisely placed throughout the body in key areas to monitor 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; where else in the body will researchers find and map these colonies? What else do these neuronal colonies and/or neuron-related structures maintain? Still in the extremely early stages, the first baby steps have been taken to map and regulate the body through these neuronal colonies, with studies pertaining to regulating disease and immune response.
The brain is the regulator of the body, controlled by gene-encoded neurons in constant epigenetic cascade, manual regulation is foreseen here also, if the cascade can be controlled, theoretically so can the whole-body regulation. And with medicalised neuropsychiatry came intricate maps of neural networks, of brain circuitry imaging mental disorders on a single-cell level, a direct result of nanotechnology and precision medicine, the game has really been stepped up, don’t be left behind. These studies honed in on the nano scale, genetic and epigenetic-gated neurons to the very single dendrite, and the workings of minutest synaptic valley.
2016 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 juggernaut that is neuroimaging, the one true non-invasive neurologically based biomarker, now crucial for validation in every step of neuroscientific 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, shaping the person, these gated-systems out of their control. Could this be 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. The progressive studies pushing the human race forward are both wondrous and scary, garnering very real emotional opposition and support, both sides as passionate as the other, this is the effect Healthinnovations has…. It’s the highly anticipated Top 10 Healthinnovations of 2016:
At number one, the top global Healthinnovations for 2016 is 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 that if these receptors are activated by binding an odorant, where the bronchi 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 that 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 that 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, it went on to regulate bronchiole contraction at a single-cell level via the newly mapped olfactory receptors. These amazing findings provide the first evidence that 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, and the way in which to view and treat diseases overall; by tapping into the human body’s own regulatory system to control disease processes, to provide damage limitation, as well as honing and improving existing systems within 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 to begin 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 that 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; or possibly resetting gene expression in the human brain to manually regulate disease manifestation and/or severity.
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, involving 236 subjects, demonstrated an overall accuracy, sensitivity and specificity rate of 100% 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 50 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 that in multiple tests, the 50 biomarkers were 100% 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 which can 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 that 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 what they’d already learned, this was repudiated by the fourth biggest Healthinnovations for 2016 from the Texas A&M College of Medicine, stunning the field of hippocampal neurogenesis. Their study showed that 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 that on average, the rats ran about 48 miles in four weeks, with neuron formation doubling in the hippocampus of these animals. This suggests that 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 number five, and the midway mark is the Rockefeller University with another great inroads for manually regulating the human body via neuronal colonies. This amazing development showed that 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. In order to deal with pathogens, resistance to infections needs to be coupled with tolerance to the delicacy of the system. It is known that different populations of macrophages are among the many types of immune cells present in intestinal tissue. 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 that muscularis macrophages carry receptors on their surface which allow them to respond to norepinephrine, a signaling substance produced by neurons. The presence of this receptor might indicate a mechanism by which neurons signal to the immune cells to put a stop to inflammation, and suggests that one of the main signals which induces a different response to infection appears to come from neurons, which are 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 have 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 which initiates adolescent synaptic pruning which goes awry in both autism and schizophrenia. During puberty the density of dendritic spines decreases by half in widespread areas of the CNS, this includes the CA1 hippocampus and temporal lobe which are 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 that GABA receptors trigger synaptic pruning at puberty in the mouse hippocampus, and that by reducing brain activity, these GABA receptors also reduce levels of a protein in the dendritic spine, known as kalirin-7, which stabilizes the scaffolding in the spine to maintain its structure. The mice which did not have these GABA receptors didn’t undergo synaptic pruning, and maintained the same high-level of brain connections throughout adolescence. However, these mice with too many brain connections, are able to learn spatial locations, but are unable to re-learn new locations after this initial learning, suggesting that 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 suggests that prefrontal brain areas in people with schizophrenia have fewer neural connections than normal. This data may suggest new, highly honed, treatments targeting GABA receptors for normalizing synaptic pruning in diseases such as autism and schizophrenia, where synaptic pruning is abnormal.
Number seven in this matchless list is from Lund University which fulfills the crucial gold-standard study. Standardisation, a pertinent last-stage of every new technology’s inception, as one would varnish or protectively coat a hand-crafted piece of furniture around the home, out of common-sense and practicality, is the finishing-touch to any new healthinnovations still. These set of studies work towards generating consistent good manufacturing practice (GMP)-grade human-pluripotent stem cell derived neural-progenitors which will mature and function in the adult brain after transplantation. Using the new markers they identified, the researchers developed a GMP-differentiation protocol for highly efficient and reproducible production of transplantable dopamine progenitors from human pluripotent stem cells. They successfully identified a specific set of markers which correlates 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 once again concentrating on the nano scale, minute, precision single-cell neurobiology. This advancement clarifies the mechanism in the brain which prevents 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 show that a molecule, known as the microtubule-associated protein 1A (MAP1A), connects NMDA glutamate receptors to microtubules as they are being transported to the synapses, stabilizing the receptors and preventing them from becoming derailed, as well as playing a crucial role in improving the overall efficiency and stability of the transportation process. This finding actually shows that in mice MAP1A plays an essential role in maintaining synaptic plasticity. Mice lacking this protein exhibited learning disabilities, and reduced synaptic plasticity attributable to disruptions of the anchoring machinery. This is because in the nerve cells of mice which lack 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 which can be effective on the receptor transport support system clarified in this study are expected to give rise to new treatment strategies for memory impairment and schizophrenia.
Now, unfortunately nearing the end of this list of remarkable innovation, in 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 will provide clinicians and therapists with a physical measure of the progress patients are making with behavioural and drug treatments, a tool that has been elusive in autism treatment until this point. ASD are characterized by impairments in social communication and restrictive, repetitive behaviours, and while behavioural symptoms are well-documented, investigations into the neurobiological underpinnings of ASD have not resulted in firm biomarkers. This set in modernism analyzed a series of 164 images from each of the 114 study participants and discovered that the brain scans of the social perception circuits only indicated ASD in boys. The team successfully showed that non-invasive, tangible brain scan data can be an effective indicator for 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.
Finally, at number ten is Tel Aviv University and Harvard University with a human study validating the second Alzheimer’s disease blood test in this tour de force. This massive betterment 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 that the more ADNP-RNA found in the blood, the fewer aggregates were found in the brain of elderly individuals, showing a clear connection between ADNP-levels in the blood and amyloid plaques in the brain. The study analyzes blood samples taken from 42 healthy adults, mild cognitive impairment (MCI) patients, and Alzheimer’s disease patients which was later validated by an independent study. Significant increases in ADNP-RNA levels were observed in patients ranging from MCI to Alzheimer’s dementia; ADNP-levels tested in plasma and serum samples, as well as white-blood cell RNA levels, distinguished among cognitively normal elderly, MCI, and Alzheimer’s dementia participants. ADNP levels tested in the blood also correlate with higher IQ in healthy older adults. These findings show a clear connection between ADNP-levels in the blood and amyloid plaques in the brain, and provides the basis to detect this biomarker in routine, non-invasive blood tests.
And there are the best of the best, the Top 10 Healthinnovations of 2016. Congratulations to everyone who made the list, it’s a great achievement. You have accomplished a reach of millions in just about every country on earth, causing excitement and inspiring your peers across the globe. And a big well-done to all health innovators who passed the stringent assessments to be published on the Healthinnovations channel! See you all in 2017!