(BEING CONTINUED FROM 23/04/17 )
A)New stem-cell based stroke treatment repairs damaged brain tissue
A team of researchers at the University of Georgia’s Regenerative Bioscience Center and ArunA Biomedical, a UGA startup company, have developed a new treatment for stroke that reduces brain damage and accelerates the brain’s natural healing tendencies in animal models. They published their findings in the journal Translational Stroke Research.
The research team led by UGA professor Steven Stice and Nasrul Hoda of Augusta University created a treatment called AB126 using extracellular vesicles (EV), fluid-filled structures known as exosomes, which are generated from human neural stem cells.
Fully able to cloak itself within the bloodstream, this type of regenerative EV therapy appears to be the most promising in overcoming the limitations of many cell therapies-with the ability for exosomes to carry and deliver multiple doses-as well as the ability to store and administer treatment. Small in size, the tiny tubular shape of an exosome allows EV therapy to cross barriers that cells cannot.
“This is truly exciting evidence, because exosomes provide a stealth-like characteristic, invisible even to the body’s own defenses,” said Stice, Georgia Research Alliance Eminent Scholar and D.W. Brooks Distinguished Professor in the College of Agricultural and Environmental Sciences. “When packaged with therapeutics, these treatments can actually change cell progression and improve functional recovery.”
Following the administration of AB126, the researchers used MRI scans to measure brain atrophy rates in preclinical, age-matched stroke models, which showed an approximately 35 percent decrease in the size of injury and 50 percent reduction in brain tissue loss — something not observed acutely in previous studies of exosome treatment for stroke.
Outside of rodents, the results were replicated by Franklin West, associate professor of animal and dairy science, and fellow RBC members using a porcine model of stroke-the only one of its kind in the U.S.
Based on these pre-clinical results, ArunA Biomedical plans to begin human studies in 2019, said Stice, who is also chief scientific officer of ArunA Biomedical.
“Until now, we had very little evidence specific to neural exosome treatment and the ability to improve motor function,” said Stice. “Just days after stroke, we saw better mobility, improved balance and measurable behavioral benefits in treated animal models.”
Named as part of the ‘stroke belt’ region, Georgia continues to exceed the national average in stroke deaths, which is the third leading cause of death in the U.S., with more than 140,000 Americans dying each year, according to the Centers for Disease Control and Prevention.
ArunA recently unveiled advances to the company’s proprietary neural cell platform for the production of exosome manufacturing. Today, ArunA’s manufacturing process positions the company to produce AB126 exosomes at a scale to meet early clinical demand. The company has plans to expand this initiative beyond stroke for preclinical studies in epilepsy, traumatic brain and spinal cord injuries later this year.
Researchers also plan to leverage collaborations with other institutions through the National Science Foundation Engineering Research Center for Cell Manufacturing Technologies, based at the Georgia Institute of Technology and supported by $20 million in NSF funding.
Stice, the UGA lead for CMaT, and industry partners like ArunA Biomedical, will develop tools and technologies for the consistent and low-cost production of high-quality living therapeutic cells that could revolutionize treatment for stroke, cancer, heart disease and other disorders.
- Robin L. Webb, Erin E. Kaiser, Shelley L. Scoville, Tyler A. Thompson, Sumbul Fatima, Chirayukumar Pandya, Karishma Sriram, Raymond L. Swetenburg, Kumar Vaibhav, Ali S. Arbab, Babak Baban, Krishnan M. Dhandapani, David C. Hess, M. N. Hoda, Steven L. Stice. Human Neural Stem Cell Extracellular Vesicles Improve Tissue and Functional Recovery in the Murine Thromboembolic Stroke Model. Translational Stroke Research, 2017; DOI: 10.1007/s12975-017-0599-2
After suffering a stroke, about three-fourths of patients exhibit some disability. The extent of a patient’s symptoms depends on the degree and location of brain tissue damage following the stroke event. This week in ACS Central Science, researchers show that by using a tailored small molecule to turn off the production of a key neuromodulator in the brain, they can dramatically reduce brain damage in stroke models in rats.
The neuromodulator is the gas hydrogen sulfide (H2S). Its production is carefully controlled in the brain. After a stroke, levels of H2S appear to be elevated, leading to brain tissue damage, but the details of how that happens are still a bit of a mystery. So, David B. Berkowitz and coworkers designed a quick way to synthesize molecules they deduced would inhibit the production of H2S. They showed in vitro that these compounds block an enzyme called CBS from making H2S by mimicking one of its other products. Peter T. H. Wong and colleagues then tested the compounds in rats.
When the new compound was injected an hour after the simulation of a stroke, the authors observed about a 70 percent reduction in the severity of the observed stroke damage. The results were even more striking with pretreatment. The authors conclude that using molecules like the ones they made will help researchers dissect the mechanism underlying H2S-mediated neuronal damage and will serve as an important starting point for the development of even more drug-like compounds that act in a similar manner.
Materials provided by American Chemical Society. Note: Content may be edited for style and length.
- Christopher D. McCune, Su Jing Chan, Matthew L. Beio, Weijun Shen, Woo Jin Chung, Laura M. Szczesniak, Chou Chai, Shu Qing Koh, Peter T.-H. Wong, David B. Berkowitz. “Zipped Synthesis” by Cross-Metathesis Provides a Cystathionine β-Synthase Inhibitor that Attenuates Cellular H2S Levels and Reduces Neuronal Infarction in a Rat Ischemic Stroke Model. ACS Central Science, 2016; DOI: 10.1021/acscentsci.6b00019
C)Paralyzed patient feels sensation again
April 10, 2018Source:California Institute of Technology
Summary:Using a tiny array of electrodes implanted in the brain’s somatosensory cortex, scientists have induced sensations of touch and movement in the hand and arm of a paralyzed man.
For the first time, scientists at Caltech have induced natural sensations in the arm of a paralyzed man by stimulating a certain region of the brain with a tiny array of electrodes. The patient has a high-level spinal cord lesion and, besides not being able to move his limbs, also cannot feel them. The work could one day allow paralyzed people using prosthetic limbs to feel physical feedback from sensors placed on these devices.
The research was done in the laboratory of Richard Andersen, James G. Boswell Professor of Neuroscience, T&C Chen Brain-Machine Interface Center Leadership Chair, and director of the T&C Chen Brain-Machine Interface Center. A paper describing the work appears in the April 10 issue of the journal eLife.
The somatosensory cortex is a strip of brain that governs bodily sensations, both proprioceptive sensations (sensations of movement or the body’s position in space) and cutaneous sensations (those of pressure, vibration, touch, and the like). Previous to the new work, neural implants targeting similar brain areas predominantly produced sensations such as tingling or buzzing in the hand. The Andersen lab’s implant is able to produce much more natural sensation via intracortical stimulation, akin to sensations experienced by the patient prior to his injury.
The patient had become paralyzed from the shoulders down three years ago after a spinal cord injury. Two arrays of tiny electrodes were surgically inserted into his somatosensory cortex. Using the arrays, the researchers stimulated neurons in the region with very small pulses of electricity. The participant reported feeling different natural sensations — such as squeezing, tapping, a sense of upward motion, and several others — that would vary in type, intensity, and location depending on the frequency, amplitude, and location of stimulation from the arrays. It is the first time such natural sensations have been induced by intracortical neural stimulation.
“It was quite interesting,” the study participant says of the sensations. “It was a lot of pinching, squeezing, movements, things like that. Hopefully it helps somebody in the future.”
Though different types of stimulation did indeed induce varying sensations, the neural codes governing specific physical sensations are still unclear. In future work, the researchers hope to determine the precise ways to place the electrodes and stimulate somatosensory brain areas in order to induce specific feelings and create a kind of dictionary of stimulations and their corresponding sensations.
The next major step, according to Andersen, is to integrate the technology with existing neural prosthetics. In 2015, Andersen’s laboratory developed brain-machine interfaces (BMIs) to connect a prosthetic robotic arm to electrodes implanted in the region of the brain that governs intentions. In this way, a paralyzed man was able to utilize the prosthetic arm to reach out, grasp a cup, and bring it to his mouth to take a drink. Connecting the device with the somatosensory cortex would create bidirectional BMIs that would enable a paralyzed person to feel again, while using prosthetic limbs.
“Currently the only feedback that is available for neural prosthetics is visual, meaning that participants can watch the brain-controlled operation of robotic limbs to make corrections,” says Andersen. “However, once an object is grasped, it is essential to also have somatosensory information to dexterously manipulate the object. Stimulation-induced somatosensory sensations have the potential added advantage of producing a sense of embodiment; for example, a participant may feel over time that the robotic limb is a part of their body.”
Materials provided by California Institute of Technology. Note: Content may be edited for style and length.
- Michelle Armenta Salas, Luke Bashford, Spencer Kellis, Matiar Jafari, HyeongChan Jo, Daniel Kramer, Kathleen Shanfield, Kelsie Pejsa, Brian Lee, Charles Y Liu, Richard A Andersen. Proprioceptive and cutaneous sensations in humans elicited by intracortical microstimulation. eLife, 2018; 7 DOI: 10.7554/eLife.32904
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