Q32 Bio Launches to Develop Novel Therapeutics Targeting Regulators of Innate and Adaptive Immunity – P&T Community

CAMBRIDGE, Mass., May 27, 2020 /PRNewswire/ --Q32 Bio, a biotechnology company developing biologics to restore healthy immune regulation, today announced the company's pipeline and plans to enter the clinic this year with its lead candidate. Enabled by a $46M Series A financing led by Atlas Venture, and a world class team and Scientific Advisory Board, Q32 Bio is advancing a portfolio of biologics targeting the body's innate and adaptive immune systems. The company has a robust product pipeline including a monoclonal antibody antagonist of the interleukin-7 receptor (IL-7R), and a complement therapeutics platform that has generated fusion proteins that downregulate complement activity specifically in disease-affected tissues. The company is led by industry veterans Michael Broxson as Chief Executive Officer, and co-founder, Shelia Violette, Ph.D., as Chief Scientific Officer and President of Research.

Q32 Bio was seeded and incubated by Atlas Venture with foundational science from renowned researchers in immunology Michael Holers, M.D. and Joshua Thurman, M.D., both from the University of Colorado, and Steven Tomlinson, Ph.D. from the Medical University of South Carolina. Dr. Holers serves as chairman of the Scientific Advisory Board, which is comprised of distinguished global experts in autoimmune and inflammatory disease.

The subsequent Series A financing included Atlas Venture, OrbiMed Advisors, Abingworth, Sanofi Ventures, University of Colorado and Children's Hospital Colorado Center for Innovation.

"Autoimmune and inflammatory diseases are driven by dysregulation of the immune response," said Mr. Broxson. "Q32 Bio has a preeminent team with expertise in both innate and adaptive immunity, a board of directors and scientific advisory board made up of leaders in our field, and a syndicate of blue-chip investors. This gives us a running start in developing therapies that may improve and save lives. I am thrilled to join Q32 Bio and look forward to advancing our first two immune-regulating therapies into first-in-human studies planned for 2020 and 2021."

Integrated Approach to Restoring Healthy Immune Regulation Q32 Bio's most advanced program, ADX-914, is a fully human anti-IL-7R antibody licensed from Bristol Myers Squibb (NYSE: BMY) that re-regulates adaptive immune function. The cytokine IL-7 has demonstrated the ability to drive several T-cell mediated pathological processes. It stimulates T-effector and T-memory cells, lowering the threshold-response to disease related antigens; inhibits the immunosuppressive function of T-regulatory cells; and promotes pathogenic autoantibody production. Inhibition of IL-7R signaling has the potential to durably and safely restore healthy immune regulation in numerous autoimmune and inflammatory diseases. Q32 Bio is advancing plans for the first-in-human trial of ADX-914 while continuing to monitor the potential impact of COVID-19 on clinical operations. Pending confirmation that trial sites are able to operate and enroll patients safely, a biomarker-guided ADX-914 Phase 1 trial is planned to start in late 2020.

Q32 Bio is developing ADX-914 (formerly known as BMS-986265) as part of an exclusive worldwide licensing agreement with Bristol Myers Squibb. Under the terms of the agreement, Bristol Myers Squibb received an upfront payment and became a minority shareholder of Q32 Bio. Bristol Myers Squibb has the potential to earn additional milestone payments subject to the achievement of certain development, regulatory and sales-based milestones, as well as tiered annual net sales royalties. Q32 Bio is solely responsible for all future development and commercialization costs of ADX-914.

Q32 Bio's lead program in innate immunity, ADX-097, is based on a groundbreaking platform providing tissue-targeted regulation of the complement system. Complement is an integral component of the innate immune system that provides a first line of defense for clearing pathogens and removing damaged cells. In a wide range of autoimmune and inflammatory diseases the complement system becomes hyperactivated, causing the immune system to attack and damage otherwise healthy tissue. Q32 Bio's proprietary and unique platform has yielded a pipeline of novel protein therapeutics that provide potent inhibition of complement in diseased tissues without long-term systemic blockade a key differentiator versus current complement therapeutics. Q32 Bio has initiated IND-enabling activities for ADX-097 and first-in-human dosing is planned for 2H 2021.

"Given their broad roles in mediating immunity, the complement system and IL-7 signaling pathways are high potential arenas for drug development," said Dave Grayzel, MD, Partner, Atlas Venture and chairman of the Q32 Bio Board of Directors. "With a best-in-class IL-7R antibody and fusion proteins designed to target the complement system at sites of activation in a unique and differentiated manner, Q32 Bio is well positioned to make a meaningful impact for patients with serious inflammatory and autoimmune diseases."

Experienced Leadership TeamMichael Broxson brings over 20 years of industry experience to Q32 Bio. He joined from Goldfinch Bio, where he was Chief Business and Operating officer. Prior to Goldfinch he served in leadership roles in business development, new product planning, strategy and finance at Takeda Pharmaceuticals. He holds BA and MSPH degrees in Toxicology from Tulane University and an MBA from the University of Chicago's Booth School of Business and is a CFA charterholder.

Shelia Violette, Ph.D., joined Q32 Bio from Atlas Venture, where she was Entrepreneur in Residence and initially co-led the formation of Q32 Bio. Previously she served in leadership roles in the Immunology Research group at Biogen, joining Stromedix as Vice President of Research and returning to Biogen as Vice President of Research, spearheading the tissue injury and fibrosis therapeutic area. She holds a Ph.D. in Pharmacology from Yale University.

About Q32 BioQ32 Bio is a biotechnology company developing therapies targeting powerful regulators of the innate and adaptive immune systems, to re-balance immunity in severe autoimmune and inflammatory diseases. Q32 Bio's lead programs, focused on the IL-7R pathway and complement system, address immune dysregulation to help patients take back control of their lives. For more information, please visit http://www.Q32bio.com.

About Atlas VentureAtlas Venture is a leading biotech venture capital firm. With the goal of doing well by doing good, the company has been building breakthrough biotech startups for over 25 years. Atlas works side by side with exceptional scientists and entrepreneurs to translate high impact science into medicines for patients. Our seed-led venture creation strategy rigorously selects and focuses investment on the most compelling opportunities to build scalable businesses and realize value. For more information, please visitwww.atlasventure.com.

About AbingworthAbingworth is a leading transatlantic life sciences investment firm. We help transform cutting-edge science into novel medicines by providing capital and expertise to top caliber management teams and building world-class companies. With offices in Menlo Park (California), Boston and London, Abingworth has invested in approximately 160 life science companies, leading to more than 40 M&A/exits and over 65 IPOs since 1973.

About OrbiMed OrbiMed is a leading healthcare investment firm, with $13 billion in assets under management. OrbiMed invests globally across the healthcare industry, from start-ups to large multinational corporations, utilizing a range of private equity funds, public equity funds, and royalty/credit funds. OrbiMed maintains offices in New York City, San Francisco, Shanghai, Hong Kong, Mumbai and Herzliya. OrbiMed seeks to be a capital provider of choice, providing tailored financing solutions and extensive global team resources to help build world-class healthcare companies.

About Sanofi VenturesSanofi Ventures is the corporate venture capital arm of Sanofi. Sanofi Ventures invests in early-stage biotech and digital health companies with innovative ideas and transformative new products and technologies of strategic interest to Sanofi. Among these areas are oncology, immunology, rare diseases, vaccines, potential cures in other core areas of Sanofi's business footprint, and digital health solutions. For more information, visitwww.sanofiventures.com.

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argenx Announces Positive Topline Results from Phase 3 ADAPT Trial of Efgartigimod in Patients with Generalized Myasthenia Gravis – GlobeNewswire

Regulated information Inside information

May 26, 2020Breda, the Netherlands / Ghent, Belgium argenx (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases and cancer, today announced positive topline data from the pivotal ADAPT trial of efgartigimod. ADAPT met its primary endpoint defined as percentage of responders on the Myasthenia Gravis Activities of Daily Living (MG-ADL) score among acetylcholine receptor-antibody positive (AChR-Ab+) generalized myasthenia gravis (gMG) patients. Responders are defined as having at least a two-point improvement on the MG-ADL score for at least four consecutive weeks. Based on these results, argenx plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) by the end of 2020.

Highlights of topline ADAPT data

The efgartigimod data showed rapid and robust responses in people with gMG, as well as a favorable tolerability profile, said James F. Howard Jr., M.D., Professor of Neurology (Neuromuscular Disease), Medicine and Allied Health, Department of Neurology, The University of North Carolina at Chapel Hill School of Medicine and principal investigator for the ADAPT trial. Patients with this devastating disease can experience chronic and potentially life-threatening muscle weakness that has a major impact on their quality of life, and more treatment options are needed. These data are very encouraging as they show efgartigimod has potential to make a meaningful impact on daily living activities, and we are hopeful they will lead to a new treatment being available for the gMG community.

With the ADAPT trial, we set out to evaluate efgartigimods ability to redefine the treatment paradigm for people living with gMG. The data showed that efgartigimod drove fast and deep responses, including in a proportion of patients who achieved minimal or no symptoms after treatment. In addition, we saw responses that lasted beyond eight or 12 weeks, supporting our plans to offer individualized dosing schedules that are purpose-fit to the variability in disease course that gMG patients experience, commented Wim Parys, M.D., Chief Medical Officer of argenx. Based on these data, we intend to submit a BLA for efgartigimod to the FDA before the end of the year, taking us one step closer to potentially making efgartigimod available to patients in 2021. All of us at argenx want to thank the patients and healthcare providers who participated in the ADAPT trial. ADAPT is the first pivotal trial of efgartigimod and these data further our confidence in its broad opportunity in other severe, IgG-mediated autoimmune diseases.

Additional ADAPT results, including secondary endpoints and prespecified analyses

Detailed data from the ADAPT trial will be submitted for presentation at a future medical meeting.

Phase 3 ADAPT Trial DesignThe Phase 3 ADAPT trial was a randomized, double-blind, placebo-controlled, multi-center, global trial evaluating the safety and efficacy of efgartigimod in patients with gMG. A total of 167 adult patients with gMG in North America, Europe and Japan enrolled in the trial and were treated. Enrolled patients had a confirmed gMG diagnosis and an MG-ADL total score of five or greater. Patients were on a stable dose of at least one gMG treatment prior to randomization, including acetylcholinesterase inhibitors, corticosteroids or nonsteroidal immunosuppressive drugs, and were required to remain on that stable dose throughout the primary trial. Patients were eligible to enroll in ADAPT regardless of antibody status, including patients with AChR antibodies (AChR-Ab+) and patients where AChR antibodies were not detected.

Patients were randomized in a 1:1 ratio to receive efgartigimod or placebo for a total of 26 weeks as part of the primary trial. ADAPT was designed to enable an individualized treatment approach with an initial treatment cycle followed by a variable number of subsequent treatment cycles. Treatment cycles consist of four infusions of efgartigimod (10mg/kg IV) or placebo at weekly intervals. Retreatment with additional treatment cycles was initiated according to clinical response. The primary endpoint was the number of AChR-Ab+ patients who achieved a response on the MG-ADL score defined by at least a two-point improvement for four or more consecutive weeks.

After the 26-week primary ADAPT trial, patients were eligible to roll-over into an open-label extension, ADAPT Plus.

About Efgartigimod

Efgartigimod is a first-in-class antibody fragment designed to reduce disease-causing immunoglobulin G (IgG) antibodies and block the IgG recycling process. Efgartigimod binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation. Blocking FcRn reduces IgG antibody levels representing a logical potential therapeutic approach for several autoimmune diseases known to be driven by disease-causing IgG antibodies, including: myasthenia gravis (MG), a chronic disease that causes muscle weakness; pemphigus vulgaris (PV), a chronic disease characterized by severe blistering of the skin; immune thrombocytopenia (ITP), a chronic bruising and bleeding disease; and chronic inflammatory demyelinating polyneuropathy (CIDP), a neurological disease leading to impaired motor function.

About Myasthenia Gravis (MG)

MG is a rare and chronic autoimmune disease where IgG antibodies disrupt communication between nerves and muscles, causing debilitating and potentially life-threatening muscle weakness. More than 85% of people with MG progress to generalized MG (gMG) within 18 months, where muscles throughout the body may be affected, resulting in extreme fatigue and difficulties with facial expression, speech, swallowing and mobility. In more life-threatening cases, MG can affect the muscles responsible for breathing. Patients with confirmed AChR antibodies account for 80-90% of the total gMG population. There are approximately 65,000 people in the United States and 20,000 people in Japan living with the disease.

Conference Call DetailsManagement will host a conference call and webcast presentation today at 2:30 p.m. Central European Summer Time (CEST) / 8:30 a.m. Eastern Daylight Time (EDT). To participate in the conference call, please select your phone number below and use the confirmation code 6295982. The webcast may be accessed on the Investors page of the argenx website at http://www.argenx.com or by clicking here.

Dial-in numbers:Please dial in 510 minutes prior to 2:30 p.m. CEST / 8:30 a.m. EDT using the number and conference ID below.

Confirmation Code: 6295982

Belgium: +32 (0)2 793 3847Belgium: 0800 484 71France: +33 (0)1 7070 0781France: 0805 101 465Netherlands: +31 (0)2 0795 6614Netherlands: 0800 023 5015UK: +44 (0) 844 481 9752UK: 0800 279 6619US: +1646 741 3167US: 1877 870 9135

About argenxargenx is a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases and cancer. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx is translating immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx is evaluating efgartigimod in multiple serious autoimmune diseases, and cusatuzumab in hematological cancers in collaboration with Janssen. argenx is also advancing several earlier stage experimental medicines within its therapeutic franchises. argenx has offices in Belgium, the United States and Japan. For more information, visit http://www.argenx.com and follow us on LinkedIn at https://www.linkedin.com/company/argenx/.

Contacts:

Beth DelGiacco, Vice President, Investor Relations (US)+1 518 424 4980bdelgiacco@argenx.com

Joke Comijn, Director Corporate Communications & Investor Relations (EU)+32 (0)477 77 29 44+32 (0)9 310 34 19JComijn@argenx.com

Forward-looking Statements

The contents of this announcement include statements that are, or may be deemed to be, forward-looking statements. These forward-looking statements can be identified by the use of forward-looking terminology, including the terms believes, estimates, anticipates, expects, intends, may, will, or should and include statements argenx makes concerning the safety, tolerability and efficacy of efgartigimod and the results of the ADAPT trial; the timing of planned regulatory submissions with the FDA and, if approved, launch in the U.S.; the therapeutic and commercial potential of efgartigimod; the opportunity of efgartigimod in other severe, IgG-mediated autoimmune diseases; and the intended results of its strategy.By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. argenxs actual results may differ materially from those predicted by the forward-looking statements as a result of various important factors, including argenxs expectations regarding its the inherent uncertainties associated with competitive developments, preclinical and clinical trial and product development activities and regulatory approval requirements; failure to demonstrate the safety, tolerability and efficacy of argenxs product candidates; final and quality controlled verification of data and the related analyses; the expense and uncertainty of obtaining regulatory approval, including from the U.S. Food and Drug Administration and European Medicines Agency; the possibility of having to conduct additional clinical trials; argenxs reliance on collaborations with third parties; estimating the commercial potential of argenxs product candidates; argenxs ability to obtain and maintain protection of intellectual property for its technologies and drugs; argenxs limited operating history; and argenxs ability to obtain additional funding for operations and to complete the development and commercialization of its product candidates. A further list and description of these risks, uncertainties and other risks can be found in argenxs U.S. Securities and Exchange Commission (SEC) filings and reports, including in argenxs most recent annual report on Form 20-F filed with the SEC as well as subsequent filings and reports filed by argenx with the SEC. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. argenx undertakes no obligation to publicly update or revise the information in this press release, including any forward-looking statements, except as may be required by law.

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Denali unveils new way of crossing blood brain barrier as the big neuroscience bets enter its clinical years – Endpoints News

Five years ago, as much of pharma began leaving neuroscience, three big-name scientists from Genentech and some A-list investors, including ARCH and Flagship, made a $217 million bet that new genetic insights and a reliance on biomarkers could bring them success. They called it Denali Therapeutics.

Still, Denali faced the problem that neuroscience developers have faced for decades: How do you get a large molecule across the blood-brain barrier, a natural defense evolved precisely to keep them out? Enzyme replacement therapy, for instance, would be a great candidate to treat several neurological disorders, but enzymes cant cross the barrier.

Now, Denali thinks theyve solved the problem, or at least part of it. In a pair of papers published inScience Translational Medicine,the South San Francisco biotech detailed the invention of a new transport vehicle to sneak large molecules past the brains gates. So far, its been used in mice and monkeys, but they wont wait long to bring it to patients: A clinical trial using it to replace an enzyme lost in people with Hunters syndrome is set to begin this year, with proof-of-concept data expected to come before 2021.

The blood-brain barrier consists in part of tightly packed endothelial cells. Since certain molecules, such as insulin, cross the barrier by first binding to receptors on these cells and then being allowed through, scientists have long tried to build antibodies that can similarly bind to these receptors and shuttle across a therapeutic cargo. But the results, over several decades, have been less than transformative.

CEO and founder Ryan Watts has been part of that search since his Genentech days. The research method he and Denalis scientists came up with began with a process called directed evolution in which a protein is induced to mutate repeatedly, until it gives rise to a protein with the qualities you want to build a protein, called an FC fragment, that binds to whats called a transferrin receptor, a node that normally imports iron into the brain. In theory, there are numerous drugs one could then hook onto that Fc fragment, but Denali first tested it with an antibody-targeting enzyme called beta-secretase. The enzyme is linked to the build-up of amyloid plaques in people with Alzheimers, and the researchers showed their vehicle reduced the amount of amyloid in mice and monkeys.

In a second study, the researchers attached an enzyme called iduronate-2-sulfatase, the critical protein that people with Hunters syndrome are missing. Without it, sugars called glycosaminoglycans build up in cells, causing abnormalities in several different organs. Shire gained approval for an enzyme replacement therapy in 2006, but it only works outside the brain (the companys erstwhile efforts to improve cognitive function yielded little promise). Using the transport vehicle, though, Denali was able to get significantly increased brain penetration of the enzyme and reduce the pathology in mice and monkeys.

Denali played up the potential versatility of their approach over other blood-brain-barrier-crossing proposals, such as bispecific antibodies, saying you can attach a greater range of therapies to their vehicle. The company has over a dozen programs including a Parkinsons one now in the clinic but the first test of the vehicle will be later this year, in 16 kids with a rare disease whose worst symptoms remain untreated.

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Neuroscience-led AI leads to launch of universal hearing aid – Med-Tech Innovation

ChatableApps has launched a universal hearing aid, using neuroscience-led artificial intelligence to empower those suffering from hearing loss to hear one-to-one conversations clearly, using an everyday smartphone and a standard pair of earbuds.

ChatableApps AI was created by reverse engineering the brain to understand how a healthy brain should work, when listening to speech. The resulting technique is called end-to-end neural speech synthesis and involves the neuroscience-led AI listening to the sound mixture of a conversation, and repeating the voice only element in real-time.

While traditional approaches attempt to label and remove sounds we arent interested in, ChatableApps proprietary artificial intelligence called VOXimity works differently, identifying the voice we want to hear, and creating a new, identical voice which sounds the same as the original but without any other background sounds.

Mark Cuban, who appears on the US version of Dragons Den and was the first investor in ChatableApps, said: "Chatable is using AI to address growing health care inequality by providing an affordable hearing aid app that helps with conversation."

Giles Tongue, ChatableApps CEO, said: Our unique ground-up AI makes our universal hearing aid the first app capable of addressing the global hearing epidemic. Following successful preclinical trials, we have decided to launch immediately due to urgent demand from Audiologists to help people struggling because of Coronavirus: With many unable to lipread due to face masks or unable to visit a hearing clinic in an emergency, our app provides a lifeline that will help people communicate.

Globally there are 466 million people with disabling hearing loss. Hearing loss affects 11 million in the UK. The high costs of traditional hearing aids, and the fact that many people arent covered by their insurance or health service around the world, they are currently going untreated.

Dr Andrew Simpson, the founding scientist of ChatableApps, holds a PhD in auditory neural signal processing and has published widely on artificial intelligence and hearing topics. Working at the intersection of auditory neuroscience and artificial intelligence has led Dr Simpson to create VOXimity, which is real-time on-device speech processing.

Dr Simpson said: "Putting an auditory cortex on a smartphone has been a dream for a long time.As far as I know this is the most advanced real-time AI that has ever done so. Its been a long road, but our preclinical trials reveal something of a medical breakthrough: a hearing aid that doesnt need hearing tests and going straight into the hands of people who cant afford a hearing aid.

At pre-clinical trials where 86% reported that the ChatableApps universal hearing aid was better for conversation than their traditional hearing aid.

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The Neuroscience of Thriving Through Crisis: How to Make Work Sustainable and Leverage the Moment – ATD

Dr. David Rock coined the term Neuroleadership and is the Director of the NeuroLeadership Institute, a global initiative bringing neuroscientists and leadership experts together to build a new science for leadership development. With operations in 24 countries, the Institute also helps large organizations operationalize brain research in order to develop better leaders and managers.

David co-edits the NeuroLeadership Journal and heads up an annual global summit. He has written many of the central academic and discussion papers that have defined the Neuroleadership field. He is the author of the business best-seller Your Brain at Work (Harper Business, 2009), as well as Quiet Leadership (Harper Collins, 2006) and the textbook Coaching with the Brain in Mind (Wiley & Sons, 2009). He blogs for the Harvard Business Review, Fortune Magazine, Psychology Today, and the Huffington Post, and is quoted widely in the media about leadership, organizational effectiveness, and the brain.

Academically, David is on the faculty and advisory board of CIMBA, an international business school based in Europe. He has been a guest lecturer at many universities including Oxford Universitys Said Business School. He is on the board of the BlueSchool, an initiative in New York City building a new approach to education. He received his professional doctorate in the Neuroscience of Leadership from Middlesex University in 2010.

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First spine surgeries performed in the region – Waushara Argus

The surgical team of providers from ThedaCare and Neuroscience Group have successfully performed the first robotic-assisted spine surgeries in Northeast and Central Wisconsin using the Mazor X Platform this week.

It is estimated that nearly 80 percent of the population will suffer from lower back pain at some point in their lives, with one in 20 of them needing surgery. As spinal surgery has evolved, more focus has been placed on new techniques often providing benefits of less blood loss, less radiation exposure, less tissue damage, and less pain and resulting opioid use.

To enhance access to specialized care close to home, ThedaCare recently installed the new Mazor X StealthTM Edition Robotic Guidance Platform. ThedaCare, in partnership with Neuroscience Group, is one of the first in the area to offer this spine surgical technology to patients and is one of the first to adopt this technology in the United States.

The Mazor X is a guide for the surgeons hands that provides a huge advance in accurate pedicle screw placement, said Randall Johnson, MD PhD, neurosurgeon at Neuroscience Group and Spine Surgery Medical Director at ThedaCare. This technology will set the standard for the future of minimally invasive and scoliosis surgery.

The Mazor X Platform enhances surgeons limited view of patients anatomy with a 3D surgical plans and analytics. This provides comprehensive information and visualization before the surgery starts, ultimately supporting the commitment to operate with precision. According to Dr. Johnson, this means the angle, width and length of every screw, is planned from the preoperative CT scan and two x-rays during surgery. Its safer for the patient and the surgical team in terms of radiation exposure as it limits the number of necessary x-rays.

A patients health and safety are top priorities for ThedaCare, said Michael Hooker, DO, Vice President and Chief Medical Officer of Acute Care at ThedaCare. By bringing new technology to the area, ThedaCare is helping promote faster recovery times, reducing postoperative pain and improving results for our patients. The staff is committed to getting patients back to doing what they love most, as quickly as possible.

Due to the COVID-19 response, much like health care systems across the country, ThedaCare made necessary adjustments to operations and services. In early May, ThedaCare began reinstating services that had previously been deferred, including surgeries.

The mission is to improve the health of the communities ThedaCare serves, and that means connecting community members to the care they need, said Lynn Detterman, Senior Vice President of ThedaCare South Region. Because of the teams tireless work through the intentional phased reopening plan, multiple safeguards are in place and are in a position to begin offering essential and routine services for illness and ongoing medical care. ThedaCare is proud to welcome technology like this to enhance care options for patients.

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First spine surgeries performed in the region - Waushara Argus

Prothena to Present at the Jefferies Virtual Healthcare Conference on June 3 – Financialbuzz.com

DUBLIN, Ireland, May 27, 2020 (GLOBE NEWSWIRE) Prothena Corporation plc (NASDAQ:PRTA), a clinical-stage neuroscience company with expertise in protein misfolding, today announced that members of its senior management team will present and participate in the Jefferies Virtual Healthcare Conference on Wednesday June 3 at 3:30 PM ET.

A webcast of the company presentation can be accessed through the investor relations section of the Companys website at http://www.prothena.com. Following the presentation, a replay of the webcast will be available on the Companys website for at least 90 days following the presentation date.

About Prothena

Prothena Corporation plc is a clinical-stage neuroscience company with expertise in protein misfolding, focused on the discovery and development of novel therapies with the potential to fundamentally change the course of devastating diseases. Fueled by its deep scientific expertise built over decades of research, Prothena is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Prothenas partnered programs include prasinezumab (PRX002/RG7935), in collaboration with Roche for the potential treatment of Parkinsons disease and other related synucleinopathies, and programs that target tau, TDP-43 and an undisclosed target in collaboration with Bristol-Myers Squibb for the potential treatment of Alzheimers disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) or other neurodegenerative diseases. Prothenas proprietary programs include PRX004 for the potential treatment of ATTR amyloidosis, and programs that target A (Amyloid beta) for the potential treatment of Alzheimers disease. For more information, please visit the Companys website at http://www.prothena.com and follow the Company on Twitter @ProthenaCorp.

Media and Investor Contact:

Ellen Rose, Head of Communications650-922-2405, ellen.rose@prothena.com

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Frog brain discovery may pave the way for repairing birth defects in humans – News-Medical.Net

A new study on the frog brain may lead to innovative ways of repairing congenital disabilities in humans.

A team of researchers from Tufts University, Universitat de Valencia, and Harvard University has discovered that the brains of developing frog embryos damaged by nicotine exposure can be repaired by using ionoceuticals that can help in the recovery of bioelectric patterns in the embryo.

The study, which was published in the journal Frontiers of Cellular Neuroscience, highlights the possibility of treatment strategies based on restoring the bioelectric blueprint or map for embryonic development. The study may pave the way for developing drugs and therapies to help repair birth defects in the future.

Nicotine induced defects in the frog embryo brain (center) can be rescued by transplanting an HCN2 expressing patch on the embryo far from the brain. Treated embryos are observed to have normal brain morphology and function (right). View of normal embryo head is shown at left. Similar results are seen when nicotine-exposed embryos are treated with ionoceutical drugs. (FB = forebrain; MB = midbrain; HB = hindbrain) Image Credit: Vaibhav Pai, Tufts University

Bioelectrical signals among cells control and guide embryonic brain development. Previous studies have shown that manipulating these signals can repair genetic defects and induce the development of healthy brain tissue.

In a study published in the Journal of Neuroscience in 2015, the same scientists revealed that bioelectric signaling controls the activity of two cell reprogramming factors, which they tested on African clawed frog embryos.

The team found that cells communicate even in long distances in the embryo by using bioelectrical signals. The cells use this data to know where to form a brain and how big the brains should be.

The findings of their current study were based on their previous research on bioelectric signals.

Now, the team aimed to see how bioelectric signals can help repair the brain damaged by nicotine.

Nicotine is a stimulant and potent parasympathomimetic alkaloid that is naturally produced in the nightshade family of plants. Nicotine is highly addictive. It is one of the most commonly abused drugs. The primary therapeutic use of nicotine is treating nicotine dependence to eliminate smoking.

Earlier studies have shown that nicotine can disrupt the normal electrical patterns in the brain of a growing embryo. It was found that it can reduce the contrast of the bioelectric blueprint, which is a map of different voltage levels around the cells. This map aids and guides the pattern and growth of organs and tissues.

Nicotine in humans has been tied to various health effects, including intrauterine fetal death, attention deficit hypersensitivity disorder (ADHD), sudden infant death, and other cognitive function deficits. It can also affect the infants memory and learning abilities.

In the study, the researchers applied nicotine to developing frog embryos to generate neural defects. They want to determine the specific interventions that can reverse the harmful effects of the chemical. In the previous study, the team identified one specific element in the natural electric signaling that controls brain development the hyperpolarization-activated cyclic nucleotide-gated channel-2 (HCN2), which was able to restore the bioelectric patterns.

In 2015, the team tried to repair the defects by using a form of gene therapy that modifies the expression of HCN2. However, in the current study, no gene was used. Instead, the team has found that the same effects can be achieved by using small molecule drugs to stimulate the HCN2 channels that are already present inside the embryo. Next, the team has demonstrated that they can reset the electrical patterning information that oversees brain development from a distant location on the embryo.

Michael Levin, the study author, and a Vannevar Bush Professor of Biology at Tufts University said that the study is a breakthrough in preventing neural tube defects and birth defects in embryos. Further, he added that when the team boosted the expression of HCN2 at a distance from the brain, such as in non-neural regions, they were still able to prevent or repair the defects in the brain.

The instructions to build a fully grown animal, including organs as complex as the brain, are distributed among all the cells of the embryo. These results suggest that we might not have to target the damaged region directly, and we can use drugs instead of genetic manipulation, which opens a lot of opportunities for biomedical deployment, Levin added.

The findings of the study have led the scientists to think that there may be a drug that activated HCN2. They can use the drug to prevent defects in the embryo.

At present, two drugs can activate HCN2 gabapentin, and lamotrigine. They are already FDA-approved and are safe-to-use.

To test their hypothesis, the team exposed the embryos to nicotine and treated them with drugs during the various stages of embryonic development.

The team discovered that 68 percent of the tadpoles who were not treated with drugs had brain defects. On the other hand, the embryos that were treated with either of the drugs had a reduction of brain defects. About only 10 percent of the frogs treated with lamotrigine and 16 percent of those treated with gabapentin had brain defects.

Our results and quantitative model identify a powerful morphogenetic control mechanism that could be targeted by future regenerative medicine exploiting ion channel modulating drugs approved for human use, the team concluded in the study.

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Frog brain discovery may pave the way for repairing birth defects in humans - News-Medical.Net

Inner Speech, Internal Monologues and Hearing Voices: Exploring the Conversations Between Our Ears – Technology Networks

Its slightly strange that we talk to ourselves inside our own head. Its even stranger that we do it virtually the whole time we are awake. Whats strangest of all is that, despite coronavirus isolation making our internal chatter all the more apparent, we dont often outwardly discuss the conversation in our head.Similarly, our scientific investigation of inner speech has made surprisingly little headway. Charles Fernyhough is a professor in the Department of Psychology at Durham University and author of The Voices Within, a book focusing on inner speech. He suggests that the first challenge is defining exactly what to call the noises we make inside our head. A lot of people talk about the inner voice, which is a term I avoid, because it is very vague and fluffy and hard to pin down.Fernyhough says that people may associate the term inner voice with concepts like gut feeling or moments of inspiration, but what he and his team study is inner speech, a formal scientific term that involves the word-based conversations we have with ourselves inside our heads. Fernyhough has argued in hisresearch that inner speech is a distinct type of auditory thinking, separate from, for example, imagining a siren going off. As well see, inner speechs developmental origins and unique characteristics separate it from these other between-our-ears phenomena.

Researchers in Fernyhoughs field have not chosen an easy area of study. Whilst behavioural neuroscientists can mimic fear responses in a mouse and neuroimaging researchers can look at highly-conserved reward pathways in non-human primates, studying inner speech in humans really requires human volunteers. These test sujects often arent particularly cooperative: People find it very hard to reflect on their own inner speech. The reason it's had little attention, publicly, culturally, but also scientifically is that it's very hard to get a grip on ones own inner speech, says Fernyhough.Fernyhoughs quest to understand inner speech began by observing outer speech at the beginning of the brains development. His research began in developmental psychology, studying how young children behaved when playing alone. Fernyhough noticed that his subjects would spend a lot of their time talking to themselves out loud. This seemed to fulfil a function beyond just annoying nearby working-from-home parents. [The children] give a strong impression, and the research supports this, that they are doing it for a reason they're doing it because it's helpful. They're getting some sort of cognitive benefit from it, says Fernyhough.

As the children aged, this helpful out-loud speech gradually stopped. Had parents just asked them to keep quiet, or was there something more complicated involved? Fernyhough found an answer in the work of influential Soviet psychologist Lev Vygotsky. Vygotsky, Fernyhough tells me, believed that speech was something that began as a purely social instrument for communication between people that over the course of development became gradually internalized. This process of internalizing, Fernyhough says, gives us tools for thinking that benefits our development.

Not all aspects of our inner speech have obvious benefits to our behavior. Anyone who has anxiously spent hours internally processing worried thoughts about an exam, only to have no time to actually study for it, might wonder why such unhelpful examples of inner speech were not chopped out at an earlier point in evolution. Surely an early human would have been much fitter to their environment if they just threw a spear straight into a mammoth without ruminating on how they were going to extract the spear later, and whether this particular mammoth was going to be as delicious as the one they had caught last winter?

Jonny Smallwood, a professor in the Department of Psychology at the University of York, has made the study of one particularly aimless form of rumination, daydreaming, his own research niche. Things like daydreaming even though they might seem "purposeless must be having some kind of quite important role in how we guide our lives, says Smallwood.

But what is that role? Smallwoods studies have looked at how people from different countries and cultures daydream. All his participants had one thing in common they tended to think about the future. Smallwood reckons that this common finding hints at why internal states like daydreaming and inner speech have become so widespread. One of the ways that the internal representation system can be selected for is because you can prepare for an interaction with another person and you can think about the kind of things that they might be happy or unhappy for you to say. Then, when you get into that circumstance, you're less likely to say the wrong thing, which might make the interaction smoother, says Smallwood.

Internal processes like inner speech and daydreaming might give us an evolutionary advantage. But the most interesting thing about these processes isnt their function, but their prevalence. Fernyhough has noted that inner speech, despite perhaps seeming to many people like the most innate behavior of all, is not ubiquitous. You certainly find that private speech in children is pretty universal. You don't find many kids who are developing in a typical way that don't use private speech. But when it comes to adults, I came across people who clearly just weren't doing much inner speech, says Fernyhough.

These internally silent volunteers instead commonly relied on imagery in their day-to-day thoughts, with pictures replacing words as their thinking tool of choice. To my mind it says it's something that a lot of humans do because it's handy. But it's by no means an essential component of consciousness, says Fernyhough. We find different ways to get to the same outcome and I think that's one of the marvels of psychology.

Variation in how we think isnt limited to whether we use words or images. Sometimes, the very nature of our thinking can become disrupted. Fernyhough became acutely aware of this when he shared his developmental psychology findings with psychiatrist colleagues, who took his comments about inner speech to be referring to auditory hallucinations, or hearing voices.

Durham University's Palace Green Library hosted an exhibition titled Hearing Voices: suffering, inspiration and the everyday in 2016-17. Image credits from Durham exhibition: Andrew Cattermole Photography

These hallucinations are most commonly linked in popular culture to the mental health disorder schizophrenia. In reality, schizophrenia is a complex disorder, and auditory hallucinations are just part of an often complex range of symptoms. The idea that hearing voices is unique to schizophrenia is also misleading, suggests Fernyhough. The experience of hearing voices is involved in all sorts of different psychiatric diagnoses, everything from post-traumatic stress disorder (PTSD) to eating disorders. It is also experienced by quite a small but significant number of people who are not mentally ill who hear voices quite regularly, but don't seek help for them because they're not troubled by them.

Is there a fundamental difference between inner speech and auditory hallucinations? This question has been the target of a project Fernyhough is helping run at Durham, funded by the Wellcome Trust, called Hearing the Voice. The study is still ongoing, but some early conclusions are that the difference between these internal states is very simple. The idea is that when somebody hears a voice, what they're actually doing is some inner speech, but for some reason, they don't recognize that they themselves made that bit of language in their heads, says Fernyhough. Its experienced as coming from somewhere else or from someone else.

What complicates this idea are the many types of both inner speech and auditory hallucinations. Fernyhough thinks that his theory will apply to some types of both experiences, but not all. Some hallucinations have acoustic properties, as if the speaker is in the room with you. Sometimes the voice has an accent or a timbre or a pitch. It's very hard to pin down what it is that makes some people have an experience that feels alien, that is distressing, especially when some people have what seems to be the same experience, but don't find it distressing, says Fernyhough. I think the only thing you can really point to is that for some reason, that experience of hearing your voice doesn't feel like you. It comes from some other author or agency. And that's what can be, as you can imagine, very distressing.

Bringing relief to that distress will require research into both "normal" and pathological forms of inner speech. To do that, psychologists rely on imaging techniques like fMRI and PET scanning. Nevertheless, the biggest advances in the field have been less to do with the hardware used and more about the way in which researchers get their participants to do inner speech.

At the beginning of these neuroimaging studies, researchers noted that when they asked their participants to engage in inner speech, areas of the brains basic language system began to light up. For most people, Fernyhough tells me, that means activation of the left hemisphere, particularly in an area at the front of the brain called Brocas area.

As we talk, our respective Brocas areas will be lighting up. Given the developmental connections between outward and inner speech, it might make sense that the same brain areas would be activated. But Fernyhough tells me these initial studies had some serious flaws.

The problem is that when we do scanning experiments like this, what we tend to do is put people into a scanner, and we say to them, right, whilst you are lying there I want you to do some inner speech, and we tell them what inner speech to do, says Fernyhough. Volunteers would be asked to say a particular phrase, such as I like football, in repetition whilst they lay inside the scanner.

Fernyhough points out that, except for the most single-minded fan, few peoples inner speech consists of repetitive statements about their love for sports. Its more often complex and chopped up into smaller chunks of thought. To try and monitor this kind of natural inner speech, Fernyhoughs team took a different approach that made use of descriptive experience sampling, a technique where subjects are prompted to note down what their inner experience was just prior to the sounding of a beeper. The process is labor-intensive, as people often need to be coached to effectively capture the details of their inner experience.

Listen to a podcast by Hearing the Voice, in which we hear testimoniescollected by Elisabeth Svanholmer (voice-hearer and mental health trainer) of how people have shared their experience of hearing voices.

Over time, Fernyhough believes the end result is much more valuable. We were able to capture the moments in which they just happened to be doing inner speech spontaneously because it's what was in their head at that time. Not because we told them to, says Fernyhough.

So was there any difference in brains doing this more natural inner speech as opposed to the repetitive, proscribed type? Fernyhough says there was a stark contrast. Using descriptive experience sampling, we got a totally different pattern of brain activations. We found activations much further back in the brain, in areas that you would associate with speech perception and understanding, not speech production. Whilst the findings need to be replicated, Fernyhough believes that if peoples brains act differently depending on whether they perform tasks spontaneously or in response to instruction, there could be ramifications for all kinds of imaging-based neuroscience.

These fundamental findings about the nature of our inner experience will only be expanded upon if neuroscience makes changes to how experiments are conducted, says Fernyhough. These changes in practice will also need to be at a fundamental level. We've got fantastic machines and software for telling us what's going on in a particular cluster of neurons and a particular moment. We're not very good at the other thing, which is asking people about their experience, of getting at the subjective quality of experience. We really have to raise our game on that.

Going forward, Fernyhough will try and bring this alternative focus to the analysis of voices as part of Hearing the Voice. Fernyhough thinks that exploring the vast range of different types of voices people hear in health and disease will raise questions not only about the brain, but about the nature of language and the mind itself. Exploring these differences could be brain researchs greatest challenge yet. But its a challenge that Fernyhough, at least, relishes: So many people in psychology and cognitive science are kind of looking for the thing that makes us all the same. And I think that's a mistaken enterprise a lot of the time. I think we are so different in so many ways, in fascinating ways. And I think our minds are just one way in which we are very, very different.

Worried about hearing voices? Visit the resources at Understanding Voices to get more information.

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Inner Speech, Internal Monologues and Hearing Voices: Exploring the Conversations Between Our Ears - Technology Networks

In the Inner Ear, UVA Finds an Essential Key to Hearing Sensitivity – University of Virginia

New research from theUniversity of Virginia School of Medicineis shedding light on the biological architecture that lets us hear and on a genetic disorder that causes both deafness and blindness.

Sihan Li, a graduate student in the lab of Jung-Bum Shin of UVAs Department of Neuroscience, has made a surprising discovery about how the hearing organ in mammals achieves its extraordinary sensitivity.

It was long suspected that tiny molecular motors maintain the proper tension in the so-called hair cell mechanoreceptors that are located in the inner ear. This tension is a key factor in how we detect sound, similar to how a taut fishing line indicates nibbling fish.

The research team led by Li and Shin demonstrated that maintaining this tension was the responsibility of a protein called Myosin-VIIa. They also found that there is not just one Myosin-VIIa, but several subtle variations that all play important roles. Problems with these protein isoforms, as the variations are known, lead to hearing loss, Shins team found. That speaks to the vital importance of these underappreciated variations in proteins.

Our sense of hearing is incredibly sensitive, and our study identified a very important component in the underlying mechanism, Shin said. Furthermore, we showed that the molecular machinery that enables hearing is much more complicated than we thought, with each protein having multiple sister forms that have distinct functions.

Myosin-VIIa is made by a genelabeled MYO7A. Mutations in that gene cause a rare genetic disorder, Usher syndrome type 1. Children with the syndrome typically are born deaf and then suffer progressive vision loss. The discovery by the Shin lab will contribute to a better understanding of this disease.

Shin and his team found that lab mice lacking proper Myosin-VIIa isoforms developed hearing loss. His work shows that the mice were able to develop hair cells, but their function was impaired and grew progressively worse. (Myosin-VIIa is also produced in the retina, the part of the eye that senses light. The Shin lab did not look at that, but his work might shed more light on how impairments in Myosin-VIIa affect vision as well.)

One of the great questions arising from the work, the researchers say, is exactly why the inner ear uses multiple isoforms of this protein. Finding those answers will help us understand an important aspect of our ability to hear, and it may one day help doctors develop new treatments for hearing loss.

After all, the flip side of the extreme sensitivity of our hearing organ is that it is also very vulnerable to stress factors, such as noise and age. We have found one important mechanism by which the ear achieves its sensitivity, Shin said. This will help us understand the harmful processes that lead to the loss of our hearing sensitivity with age or due to noise trauma, laying the foundation for the development of preventative and therapeutic strategies.

The researchers havepublished their findings in the scientific journal Nature Communications. The studys authors were Li, Andrew Mecca, Jeewoo Kim, Giusy A. Caprara, Elizabeth L. Wagner, Ting-Ting Du,Leonid Petrov, Wenhao Xu, Runjia Cui, Ivan T. Rebustini, Bechara Kachar, Anthony W. Peng and Shin.

The research was a collaboration with laboratories at the University of Colorado and the National Institute of Health, and was supported by the NIHs National Institute for Deafness and Other Communication Disorders, grants R01DC014254, R56DC017724 and R01DC016868, and by NIDCD Intramural Research Program Z01-DC000002.

To keep up with the latest medical research news from UVA, subscribe to theMaking of Medicineblog.

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In the Inner Ear, UVA Finds an Essential Key to Hearing Sensitivity - University of Virginia