Tuesday, 9 July 2013

Neurotechnology: The Growing Brain Market and Latest Neurotech Breakthroughs

“If we want to make the best products, we also have to invest in the best ideas... Every dollar we invested to map the human genome returned $140 to our economy... Today, our scientists are mapping the human brain to unlock the answers to Alzheimer's... Now is not the time to cut these job-creating investments in science and innovation. Now is the time to reach a level of research and development not seen since the height of the Space Race”

                                                    -President Barack Obama, 2013 State of the Union address

“It’s all in the mind” seems to be one of humanity’s age-old mottos whose meaning has only grown more persuasive against the test of time. Ailments previously deemed peripheral based purely on their symptoms are being exposed for having deep roots in the brain as quickly as our knowledge of grey matter is expanding, so much so that many of over 600 known neurological disorders now top the leading disease list in the developed world (Table 1). In Europe, 38% of the population is said to be affected by brain disorders annually[i], whose burden in 2010 was estimated to be €798 billion, taking into account treatment costs as well as lost productivity. And the general consensus among physicians is—incidences of neuro-disorders, such as migraine, autism, Parkinson’s disease and multiple sclerosis is visibly on the rise. Over the coming years the European Brain Council has forecasted a further 20% increase in neurologic illness in the EU[ii].

To exacerbate the problem, ageing populations have never before borne so much impact on the global total. As cardiovascular, infectious and oncology treatments ameliorated, so has survivability and thus the incidence of diseases of the “old age”, such as dementia and Alzheimer’s disease, strokes, Parkinson’s disease and progressive hearing loss. Alzheimer’s disease and stroke have been identified as the fastest-growing threats to US health, ahead of autoimmune disorders and diabetes[iii].

And perhaps the worst news is—Big Pharma has so far yielded sub-optimal treatments for neurological disorders, as success rates of neuropharmaceuticals in costly clinical trials have been excruciatingly poor in recent years. For instance, Alzheimer's disease (AD) researchers and patients had to face a long string of disappointments, as one promising AD therapy after another have failed to stop, or even slow down the disease. 2012 witnessed a fascinating race to the finish line between two anti-β amyloid monoclonal antibodies - Pfizer/Johnson&Johnson's Bapineuzumab ("Bapi") vs. Eli Lilly's Solanezumab ("Sola"). Both contenders tried to make history by altering the Alzheimer's disease treatment paradigm, but ended up failing in two of the biggest phase III studies of the year, having likely spent at least $400 million each on the drugs’ development. 

TABLE 1. LEADING NEUROLOGICAL DISORDERS IN THE US, 2010/11

Disease

Prevalence/ Incidence
Economic Burden (incl. prod. loss) (US$)

Available treatment(s)
Chronic pain

50 million

635 billion
OTC pain relievers, anti-inflammatory steroids, therapy (physical & psychological), Medical Devices: Neurostimulators, Patient Controlled Analgesia
Depression (major)

46.4 million

16 billion
Medication: Selective serotonin reuptake inhibitors (SSRIs), Serotonin and norepinephrine reuptake inhibitors (SNRIs), Norepinephrine and dopamine reuptake inhibitors (NDRIs), others; Medical devices: deep Transcranial Magnetic Stimulation (TMS), Vagus Nerve Stimulation (VNS)
Migraines/ cluster headaches
37 million
20 billion
OTC pain relievers, anti-inflammatory steroids, tripans, ergotamines, triptan+anti-emetic combination therapy, Botulinum toxin (Botox)
Hearing loss/deafness
37 million
14.75 billion
Hearing aids, cochlear implants
Bipolar disorder
5.7 million
42 billion
Mood stabilizers: Lithium, anticonvulsants, antipsychotics; Antidepressants,; Medical device: deepTMS (under investigation by Brainsway Israel)
Alzheimer’s disease
5.4 million
216 billion
Cholinesterase inhibitors: donepezine, rivastigmine, galantamine; Glutamate blocker: memantine
Autism spectrum disorders
3.5 million
35 billion
Virtually no medication – antidepressants occasionally used to treat symptoms; educational programs
Schizophrenia
3.4 million
32 billion
Typical antipsychotics, Atypical antipsychotics; Medical device: deepTMS (under investigation by Brainsway Israel)
Epilepsy
3 million
17.6 billion
Anti-epileptic drugs (AEDs): sodium valproate, carbamazepine, lamotrigine, topamax, vigabatrin; Medical device: VNS
Brain/head injury
1.7 million annually
48 billion
Neurosurgery, physical therapy
Blindness
1.3 million

Retinal prosthesis, visual cortex neuroprosthesis (under development), stem cell therapy (under development)
Stroke
795,000 annually
38.6 billion
Hemorrhagic: anticoagulants, surgery; Ischemic: clot busters, surgical clot removal (3-4-hour window); Sphenopalatine Ganglion (SPG) stimulation (24-hour window—under investigation by BrainsGate Israel)
Parkinson’s disease
500,000
23 billion
Levodopa; Dopamine agonists: pramipexole, ropinirole; Catechol O-methyltransferase (COMT) inhibitors, Monoamine oxidase-B (MAO-B) inhibitors; Medical devices: Activa® implanted brain stimulator, deepTMS (under investigation by Brainsway Israel)
Multiple sclerosis
400,000
10 billion
Interferon-beta-1a and -1b, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate; Stem Cell therapy: currently in clinical trials
Spinal cord injury
12,000 annually
14.5 billion
Neuroprosthetics, Stem Cell Therapy, antioxidant medication (methylprednisolone, lazaroids)
Amyotrophic Lateral Sclerosis (ALS)
5,600 annually
6 billion
Riluzole (only FDA-approved medication); Clinical trials: Arimoclomol, tirasemtiv, NurOwn™-adult stem cell therapy (under investigation by BrainStorm Cell Therapeutics Israel)





































































Perhaps the most significant contributing factor to the Golden Age of Neuroscience has been the rapid advancement of our understanding of this field at the basic level. Rapidly growing annual numbers of academic neuroscience publications bear testimony to the intensification of research in this sphere (fig. WE KNOW MORE


Perhaps the most significant contributing factor to the Golden Age of Neuroscience has been the rapid advancement of our understanding of this field at the basic level. Rapidly growing annual numbers of academic neuroscience publications bear testimony to the intensification of research in this sphere (fig. 1), but neuroscience success is even more evident in the highly-publicized neuro-breakthroughs of late, and in the number of academic and government initiatives which have been launched in recent years.


Vital signs seem to point towards the fact that the neuroscience revolution happening today bears striking resemblance to the biotechnology revolution circa 2000, which witnessed the tremendous efforts to sequence the human genome and resulted in colossal leaps in spheres such as genetic engineering and bacterial- and plant-derived production. 

The President of the USA is a heavy investor this time around, with US$ 100 million to spend in just one year on novel neuro-technologies and brain mapping—outshined only by the EU, whose commitment to a novel EU Brain Project was recently unveiled with a whopping €1.19 billion pledge. One needn’t be an expert in the field to sense that something big is happening. 

FIGURE 1. NUMBER OF NEUROSCIENCE PUBLICATIONS, 1950-2012, PUBMED[1]



















The SOCIETY FOR NEUROSCIENCE (SfN) was founded in Washington, D.C. in 1969, and is now the largest professional society for basic neuroscientists and physicians in the world. SfN has been a strong advocator of academic neuroscience and has played a pivotal role in funding and investment in the basic research of grey matter.




The society receives government grants, stages annual high-profile neuroscience meetings of over 30,000 attendees from 75 countries, and runs The Journal of Neuroscience - the world’s most cited neuroscience journal which publishes more research than the next five leading neuroscience journals combined. It is of no surprise that the health of SfN is often cited as a key indicator of the success of the scientific field itself. Over the past decade the society has gained nearly 20,000 members from across the world, and has grown its revenue, 23% of which originates from the scientific journal, by 10% in just eight years (fig. 2).



FIGURE 2. SOCIETY FOR NEUROSCIENCE MEMBERSHIP & REVENUE GROWTH, 2000-2012 
Basic neuroscience indicators tell a tale of a rapidly growing R&D environment which is continuously gaining new members and producing qualitative output. The Journal of Neuroscience has doubled the number of publications it contains since 2001—a growth rate which is unmatched by any other journal in the life science field, but what are the emanating breakthroughs which scientists are so eager to share with the world? Below are some examples of what neuroscience has accomplished in recent years.


MIND READING

Using electrodes to detect spikes in brain activity, scientists have been able to map areas of the brain responsible for a plethora of thoughts, actions and emotions. Back in 2007 scientists were able to predict with astonishing accuracy whether a subject would decide to add or subtract a number based on their brain activity in an fMRI scanner. However, already at the dawn of the new decade fMRI brain mapping achieved a much more incredible feat: reading and replicating vision. Subjects were asked to watch short clips inside an fMRI scanner, whose output scientists used to externally replicate clips of what the person was seeing. With this level of accuracy, it is only a matter of time before mind-reading becomes as easy as, well, reading.

STILLS FROM ACTUAL CLIPS SHOWN TO SUBJECTS (TOP) AND THE EQUIVALENT FMRI READINGS OF THE BRAIN (BOTTOM)


Image source; shinji nishimoto

Neuroscientists demonstrated their mind-reading prowess by quite literally communicating with a comatose patient with the use of an fMRI scanner. A man believed to be in a vegetative state for 12 years was able to communicate to doctors that he was not in pain, kick-starting what has since become a revolution in our understanding of the comatose state.


The occurrence caused medical books to be rewritten, as it gave us the ability to communicate with thousands of patients previously “trapped in their own skulls”, like Israel’s ex-PM Ariel Sharon, who has been in a coma following a stroke seven years ago.

In January of 2013 physicians at Beersheba’s Soroka Medical Centre announced that fMRI scan results of Sharon’s brain demonstrated significant activity, as MRI spikes were documented in response to images and voices of family members shown and played to the patient.


To advance fMRI matters further, researchers at Bar-Ilan University in Israel have used the scanner to read motion signals from a student’s brain and wirelessly transmit them to a thought-controlled robot thousands of miles away—at a laboratory in France.  The development is part of an international initiative called “Virtual Embodiment and Robotic Re-Embodiment” (VERE). The fMRI scannee could see a video relayed from a camera attached to the robot, and direct the robot as he wished by thinking motion, and thus creating certain discernible activity spikes for the robot to obey.

NEUROGENESIS and STEM CELL TRANSPLANTS FOR NEUROLOGICAL DEFICITS

"For more than a century, medical science firmly believed that our brain
could not repair itself and that we were born with all the brain cells we would ever have."
-Society for Neuroscience, 2007


Just six years ago aspiring neuroscientists would have been taught that brains are born with a set amount of neurons, and, whilst new synapses (or neuronal intersections) are able to form throughout a lifetime, new nerve cells are no longer generated within the brain. But researchers have recently delivered more uplifting news: neurogenesis has been documented to occur in several brain areas: the hippocampus, responsible for memory formation, the olfactory bulb, responsible for the sense of smell, and the subventricular zone, which has been likened to the neuro-stem-cell “breeding ground” in the brain. About 10,000 new neurons daily are now said to be born in the olfactory and hippocampal areas.

Rapidly putting the newfound knowledge to use, researchers at the University of Wisconsin-Madison have accomplished a notable feat in stem cell research, having transformed human embryonic stem cells into neuro-regenarative cells in the brains of neuro-deficient mice. Following transplantation, the mice were able to regain their abilities to learn and remember.
Once we know that adult neurogenesis takes place, it is likely to be a matter of time before scientists elucidate the mechanisms which guide new neuron formation, and are able to apply these to other, non-neurogenerative areas of the brain—an accomplishment which would have tremendous implications.

NEUROPROSTHETICS and THOUGHT-CONTROLLED ROBOTS


Basic knowledge of the motor cortex has reached the level of excellent in recent years, with thought-powered robot limbs not only doing their owners’ precise bidding, but also offering their brains sensory input in return. In other words, whilst neuroprosthetic wearers had to rely solely on their vision when reaching for an item with, for instance, a thought-powered arm, scientists are now beginning to devise cunning ways of allowing the users to feel the object their prosthetic is interacting with. Sense-able neuroprosthetics could utterly revolutionize this field, and have wider-reaching implications in sectors such as gaming and technology.
Image credit: Rehabilitation Institute of Chicago


Every wireless technology started with a wire, and neuroprosthetics are no exception. Normally bulky neuroprosthetic electrodes have to be implanted into the brain, but scientists at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), part of the NIH in the US, have built a compact, self-contained sensor which can record and relay the activity of small groups of cells wirelessly (and invisibly). The sensor is the size of a baby aspirin and is made of silicon containing 100 hair-thin electrodes[i]. Not only is this technology much more compact and aesthetically pleasing than its predecessors, but it also offers unfathomable opportunities for thought-control of—pretty much anything—in stealth mode.

CURING BLINDNESS



Image credit: Martin Cleaver/AP

In February of 2013 a monumental breakthrough testified to neurotechnology’s legitimacy when the first ever bionic eye received marketing approval from the FDA. The Argus II Retinal Prosthesis system, marketed by Second Sight Medical Products, provides electrical stimulation to the retina in patients suffering from retinitis pigmentosa—a degenerative disease which is caused by dystrophy of the retinal pigment epithelium. The device is a retinal implant which relays external images to the brain by stimulating cells in the retina via implanted electrodes.


A step further in the technology may soon be taken by Israeli Nano Retina Inc: the company’s artificial retina technology Bio-retina incorporates nano-size components in a tiny, flat implant that is implanted by a small incision and “gluing” of the device to the damaged retina. The sensors transform naturally received light into an electrical signal that stimulates the neurons, which send the pictures received by Bio-Retina to the brain. The technology is due to embark on clinical trials by 2015.



Success of devices like Argus II and Bio-retina also provides immense hope for people who have been affected by blindness since a very young age. For some time now it has been known that blind people are able to “see” just with their brains, and a prosthetic device which detects the external environment and generates basic images in the brain, bypassing the retina, is only half a decade away. Currently, a team of scientists at the University of Texas are generating a detailed map of the visual cortex, and are hoping to begin working on a visual prosthetic device which would communicate directly with this brain area.


SAMSUNG’S THOUGHT-CONTROLLED TABLET

Researchers at Samsung’s Emerging Technology Lab, in collaboration with the University of Texas, are exploring users’ ability to launch applications with the power of their thoughts in a novel Galaxy Note 10.1 interface. The technology would require the user to wear an Electroenchepalography (EEG) cap which would translate thought into basic functions like powering a device on and off, selecting a contact or a song from a list, or launching an application, and much more refined actions in the future.
Although the company does not intend to make a brain-controlled phone or tablet in the near future, Samsung’s goal is to demonstrate and ameliorate the feasibility of such an interface, which would be particularly useful to people unable to interact with devices due to mobility issues.


AN electroencephalography (EEG) cap, able to read brain activity and communicate it to an electronic interface
Image Credit: Samsung

Although we may not see EEG-clad commuters on the bus playing telepathic Sudoku any time soon, the recent neurotech developments herald a quiescent truth: in this lifetime we are likelier than not to witness a world where thought alone suffices to command the electronic power around us.  




[i] "Wireless, Implanted Sensor Broadens Range of Brain Research." U.S National Library of Medicine. N.p., 19 Mar. 2013. Web. 11 May 2013.http://www.nih.gov/news/health/mar2013/nibib-19.htm


[1] The number of annual publications was extrapolated based on a publication search on the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed – a National Center for Biotechnology Information, U.S. National Library of Medicine database), using the search term “neuron”




[i] "Growing Brain Disorders Lead to Call for More Research." British Neuroscience Association. N.p., 7 Jan. 2013. Web. 11 May 2013; http://www.bna.org.uk/news/view.php?permalink=SIXTE0PS9P
[ii] "Neurological Diseases on the Rise." European-Hospital. N.p., 21 June 2010. Web. 11 May 2013.; http://www.european-hospital.com/en/article/7274-Neurological_diseases_on_the_rise.html
[iii] Fox, Maggie. "Alzheimer's Fastest-growing Health Threat, Report Says." NBC News. N.p., 5 Mar. 2013. Web. 11 May 2013; http://vitals.nbcnews.com/_news/2013/03/05/17196908-alzheimers-fastest-growing-health-threat-report-says?lite