Bioelectronics-Based Platforms Seek to Address Inflammatory Conditions in Vital Organs, Including Acute Organ Failure and Cell/Tissue Engineering  /  Oct 6, 2015

Endonovo Therapeutics, an innovative biotechnology company developing bioelectronic products and therapies for regenerative medicine, announced two bioelectronic-based platforms for regenerative medicine. Immunotronics™, a non-invasive and non-implantable immuno-regulatory device designed to treat inflammatory conditions in vital organs, including acute organ failure; and Cytotronics™, a proprietary bioelectronic-based method of expanding and manipulating cells for the creation of cell therapies and tissue engineering.

Bioelectronics/Electroceuticals have raised significant attention due to their potential ability in treating a wide array of conditions including heart failure, asthma, diabetes, incontinence and arthritis while reducing unwanted side effects associated with the use of drugs. Last year the National Institutes of Health (NIH) announced a $248-million effort to map the body’s electrical wiring and develop electroceuticals. It will announce this upcoming autumn the first funding from the Stimulating Peripheral Activity to Relieve Conditions (SPARC) program. Additionally, DARPA, the Pentagon’s blue-skies research arm, will announce the recipients of its $80 million ElectRx initiative, a program that is part of the defense agency’s year-old biotech unit designed to advance discoveries that may help wounded warriors and others. GlaxoSmithKline, is leading the private sector’s funding of electroceuticals by investing up to $50 million in bioelectronic startups and $5 million more in basic research to map the body’s electrical wiring and how it may affect chronic diseases. Endonovo is concentrating its efforts on inflammatory conditions in vital organs and previously announced it’s in the pre-clinical phase of assessing its proprietary Immunotronic technology in the treatment of chronic and acute inflammatory conditions in the liver, including fulminant liver failure. Endonovo Chief Medical Officer, Leonard Makowka, MD, PhD, said, “Making the transition from pharmaceutical based treatment to the use of devices for treatment would be of substantial benefit to not only the patients, but the healthcare system as a whole. One of the considerable advantages of our technology is that unlike neuromodulation-based therapies, our Immunotronic platform is a non-invasive, non-implantable device for treating inflammatory conditions in vital organs.”

Research and development of Endonovo’s Immunotronic™ technology spans over 20 years and dates back to the National Aeronautics and Space Administration’s (NASA) space program where researchers were seeking to develop non-invasive treatments for injuries astronauts might experience during long-term space exploration. The origin of the Company’s Cytotronics™ platform dates back to experiments aboard the Space Shuttle benefiting from over 15 years of private research to advance the technology from basic research conducted at NASA to the current development of large scale methods for cell expansion and manipulation in the creation of cell therapies and tissue engineering. Endonovo Chief Scientist, Donnie Rudd, PhD. commented, “We have greatly advanced the technology well beyond the original NASA experiments on cell growth. Our Cytotronics platform is not only valuable in expanding cells, such as cord blood cells, but is also particularly suited for tissue engineering applications.” Alan Collier, CEO of Endonovo said, “We have spent the last year evaluating the regenerative medicine landscape, pursuant to how our product best suited all the possible applications of our platforms while strengthening our intellectual property. We are now well positioned as a company to raise capital for advancing and commercializing our bioelectronic approach to regenerative medicine.”

Neural probes combine optics, electronics, and drug treatments
by Antonio Regalado  /  April 21, 2015

Various powerful new tools for exploring and manipulating the brain have been developed over the last few years. Some use electronics, while others use light or chemicals. At one MIT lab, materials scientist Polina Anikeeva has hit on a way to manufacture what amounts to a brain-science Swiss Army knife. The neural probes she builds carry light while collecting and transmitting electricity, and they also have tiny channels through which to pump drugs. That’s an advance over metal wires or silicon electrodes conventionally used to study neurons. Anikeeva makes the probes by assembling polymers and metals into large-scale blocks, or preforms, and then stretching them into flexible, ultrathin fibers. Multifunctional fibers offer new ways to study animal behavior, since they can record from neurons as well as stimulating them. New types of medical technology could also result. Imagine, as Anikeeva does, bionic wiring that bridges a spinal-cord injury, collecting electrical signals from the brain and transmitting them to the muscles of a paralyzed hand. Anikeeva made her first multifunctional probe while studying at Stanford. It was crude: she simply wrapped metal wires around a glass filament. But this made it possible to combine standard electrode measurements with a new technology, optogenetics, in which light is fired at neurons to activate them or shut them down.

Now Anikeeva, a professor of materials science and engineering, makes probes using a fiber-drawing technology developed by another MIT researcher, Yoel Fink. It’s based on the way silica is heated and pulled to form telecommunications fiber. But it works at lower temperatures, at which many useful polymers become soft enough to stretch. Polymer fibers have a couple of important advantages. One is that they are flexible and mimic the physical properties of tissue. That could allow them to work longer than the stiff metal electrodes neuroscientists have relied on, permitting long-term studies in animals. The second feature of the fibers is that they can combine many functions. Probes made so far have incorporated as many as 36 microwires, optical waveguides, and hollow channels for carrying medicine. There’s no reason not to incorporate sensors to measure temperature or pressure as well.

Inside the body, the right materials and structures might even entice nerves to attach to the fibers, the way bone fuses to a hip implant. The fiber-drawing process shrinks large patterns into microscopic ones, preserving the details. But there are challenges. The tiny wires and tubes have to be stripped, splayed, and soldered by hand to connect them to components such as a recording device a mouse wears on its head. That’s quite a nightmare, says Andres Canales, a graduate student, who hopes to resolve the problem. Will polymer bio-wires be what ultimately cures paralysis—say, by ferrying nerve signals across an injured spinal cord? “I think it will be a version of this technology, a more sophisticated version,” says Anikeeva. “At least we are going to pursue this route.”

Hacking the Nervous System
by Gaia Vince  /  26 May 2015

“In ‘Hacking the nervous system’, I wrote about doctors who have successfully treated patients with rheumatoid arthritis by stimulating their vagus nerve with a pacemaker. This restores inflammation’s ‘off switch’ in the spleen, releasing neurotransmitters that reinstate proper regulation of inflammatory immune proteins. The result is less inflammation in the joints, less pain, and reduction of other symptoms of rheumatoid arthritis. The vagus nerve is involved in many other organs, so neurologists and immunologists are also investigating bioelectronic vagal therapies for inflammatory bowel disease, diabetes, obesity, cancer and asthma. But the vagus is just one target for electrical therapy, and scientists are beginning to explore other possibilities, too. These include targeting the splenic, splanchnic and hepatic nerve networks that run through the body’s organs, and using deep brain stimulation to treat disorders like Parkinson’s and Alzheimer’s.

Some researchers believe electronic implants that hack the nervous system will one day replace drugs for many conditions. And pharmaceutical companies seem to agree: for example, GlaxoSmithKline is investing billions in bioelectronic innovation, even offering a $1 million prize to the first team to create a device that can “read and write the body’s electrical language” – by which they mean influence an organ’s function using accurate electrical signals. The US government is also investing in the field through the $250 million SPARC initiative and the ElectRx programme. The challenges remain daunting, though. For a start, we don’t understand the body’s electrical language: the tens of thousands of nerve fibres in the vagus alone are not fully mapped, let alone their signals deciphered. Researchers at Imperial College London are working on that translation task. Stephen Bloom and Chris Toumazou have placed vagus nerve stimulators at the top of rats’ stomachs to record and read the signals sent to the brain to indicate fullness or the presence of different types of food. “The idea is that we should eventually be able to mimic the signals electrically to trick the mind into feeling full or desiring healthier foods,” Bloom explains. “The vagus does detect the type of food you eat, whether it’s protein, fat or high-calorie. And the brain feeds back, making us want certain foods, which can be unhealthy in obese people.”

But even if we could record and replicate signals, such as one from the stomach to the brain to report high levels of protein, challenges remain. For example, creating an implant device small enough yet powerful and reliable enough to run the complex microprocessor chip is far beyond our current capabilities. Nevertheless, the technology is advancing rapidly with smaller pacemakers and implants and new techniques, including laser-firing brain implants that use optogenetics rather than wires to trigger nerve impulses. The dream is to deliver precise, targeted therapy to groups of cells to promote the release of the body’s natural hormone or immune responses, dial down over-production of cells, or deploy other types of therapy, such as releasing implanted drugs at certain times and doses. The precision is possible because nerves branch in a highly specific and fixed geographical way. So treatment could be aimed at a tumour in a particular location by targeting the peripheral nerve that goes to the left side of the right lung, for example, rather than relying on the systemic approach of chemotherapy and the side-effects that entails. The field is very young, and it’s certainly not time to throw the medications away, but with early successes in inflammatory disease, obesity and epilepsy, bioelectronic medicine has made an exciting debut.”

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