Neuroscience

Benefits of Exercise May Vary Greatly in Primary Mitochondrial Disease – Neuroscience News

Summary: The benefits of endurance exercise can vary based on the mutation types associated with primary mitochondrial disease, a new study reports.

Source: CHOP

Mitochondria serve as the main source of energy production in our cells, and endurance exercise is generally known to improve the function of mitochondria. However, the benefits of exercise in patients with primary mitochondrial diseases, which are heterogeneous and caused by a variety of genetic mutations, were largely unknown.

In a new study, researchers at Childrens Hospital of Philadelphia (CHOP) demonstrated that the benefits of endurance exercise can vary based on the type of mutation involved inmitochondrial disease, and while the benefits of exercise outweigh the risks, the mitochondrial genetic status of patients should be taken into consideration when recommending exercise as therapy.

The findings were published online today by theProceedings of the National Academy of Sciences.

Primary mitochondrial diseases represent the most prevalent inheritedmetabolic disorders, affecting approximately 1 in every 4,200 people. These disorders can be caused by hundreds of different mutations in the nuclear DNA (DNA within our cells) or mitochondrial DNA (mtDNA, or the DNA within the mitochondria within our cells).

Universal treatments for these patients are limited. However, endurance exercise has been shown to improve mitochondrial function in healthy people and reduce the risk of developing secondary metabolic disorders like diabetes or neurodegenerative disorders.

However, these recommendations were based on healthy people without primary mitochondrial disease. Therefore, researchers wanted to determine effectiveness for these patients and whether they are actually benefitting from endurance exercise.

There was not a consensus among clinicians who see patients with mitochondrial disease whether endurance exercise truly offers benefits, said Patrick Schaefer, Ph.D., a postdoctoral fellow at the Center for Mitochondrial and Epigenomic Medicine at CHOP and first author of the study.

Exercise helps create more mitochondria, but if those mitochondria still have the mutations associated with primary mitochondrial disease, there is a chance that exercise may put some patients at risk.

Because of the heterogeneity of primary mitochondrial disease among patients, the researchers used animal models to study five mutations responsible for the disease.

The goal of the study was to determine the relationship between mitochondrial mutations, endurance exercise response, and the underlying molecular pathways in these models with distinct mitochondrialmutations.

The study found that endurance exercise had different impacts on the models depending on the mutation involved. Exercise improved response in the model with the mtDNA ND6 mutation in complex I.

The model with a CO1 mutation affecting complex IV showed significantly fewer positive effects related to exercise, and the model with a ND5 complex 1 mutation did not respond to exercise at all. In the model that was deficient in nuclear DNA Ant1, endurance exercise actually worsened cardiomyopathy.

Additionally, the researchers were able to correlate the gene expression profile of skeletal muscle and heart in the model with exercise response and identifiedoxidative phosphorylation, amino acid metabolism, and cell cycle regulation as key pathways in exercise response, suggesting how the model might be adapted to study exercise responses in humans with primary mitochondrial disease.

Despite mixed responses of the models used in this study, the authors note that thebenefits of exerciseoutweigh the risks in most cases. However, the physical and mitochondrial status of the patient should be taken into account when recommending therapeutic exercises.

Additionally, the study could help researchers identify biomarkers and pathways to help predict the mitochondrial response toexerciseboth in mitochondrial patients and the healthy population harboring different mitochondrial haplogroups.

This work is of fundamental importance in demonstrating that individuals with different mitochondrial bioenergetics will respond differently toendurance exercise, said senior study author Douglas C. Wallace, Ph.D., director of the Center for Mitochondrial and Epigenomic Medicine at CHOP and the Michael and Charles Barnett Endowed Chair in Pediatric Mitochondrial Medicine and Metabolic Diseases.

This is of broad relevance to individuals ranging from athletes to patients with mitochondrial disease, and everyone in between.

Author: Press OfficeSource: CHOPContact: Press Office CHOPImage: The image is in the public domain

Original Research: Closed access.Mitochondrial mutations alter endurance exercise response and determinants in mice by Patrick M. Schaefer et al. PNAS

Abstract

Mitochondrial mutations alter endurance exercise response and determinants in mice

Primary mitochondrial diseases (PMDs) are a heterogeneous group of metabolic disorders that can be caused by hundreds of mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) genes. Current therapeutic approaches are limited, although one approach has been exercise training.

Endurance exercise is known to improve mitochondrial function in heathy subjects and reduce risk for secondary metabolic disorders such as diabetes or neurodegenerative disorders. However, in PMDs the benefit of endurance exercise is unclear, and exercise might be beneficial for some mitochondrial disorders but contraindicated in others.

Here we investigate the effect of an endurance exercise regimen in mouse models for PMDs harboring distinct mitochondrial mutations.

We show that while an mtDNA ND6 mutation in complex I demonstrated improvement in response to exercise, mice with a CO1 mutation affecting complex IV showed significantly fewer positive effects, and mice with an ND5 complex I mutation did not respond to exercise at all. For mice deficient in the nDNA adenine nucleotide translocase 1 (Ant1), endurance exercise actually worsened the dilated cardiomyopathy.

Correlating the gene expression profile of skeletal muscle and heart with the physiologic exercise response identified oxidative phosphorylation, amino acid metabolism, matrisome (extracellular matrix [ECM]) structure, and cell cycle regulation as key pathways in the exercise response. This emphasizes the crucial role of mitochondria in determining the exercise capacity and exercise response.

Consequently, the benefit of endurance exercise in PMDs strongly depends on the underlying mutation, although our results suggest a general beneficial effect.

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Benefits of Exercise May Vary Greatly in Primary Mitochondrial Disease - Neuroscience News

Neuroscience

WVU Today | WVU experiential business learning, health care outreach and personalized nursing bolstered by couple’s $1.8M gift – WVU Today

Rusty and Kimberly Hutson (at center) pose with children (from left) Conner, Parker, Tanner and Hannah. (Submitted Photo)

A $1.8 million gift to West Virginia University from Mountain State natives Kimberly and Rusty Hutson, Jr., will bolster education, health care and outreach efforts to aid residents across the state.

The Hutsons contribution provides $1 million to support namesake fellowships in experiential learning and applied service at the John Chambers College of Business and Economics, $400,000 to aid the West Virginia Faith Community Nursing Initiative at the School of Nursing, and $400,000 to expand personalized care for neuroscience patients and their families at the Rockefeller Neuroscience Institute.

Kimberly and I are thrilled to give to these three quality programs at WVU, Rusty Hutson said.We have been blessed as a family, and we are passionate about giving back to our home state that we love so much. These gifts are strategic for us as a family, as we look to assist in enhancing quality health care for rural areas of the state as well as provide support for the world-class Rockefeller Neuroscience Institute.In addition, the Hutson Fellows program will not only assist students in furthering their business education in a real business setting but will encourage them to remain in West Virginia as they begin their business careers. We are honored to provide the financial support needed to develop and enhanceall three programs.

The Rusty & Kimberly Hutson Fellowships in Experiential Learning will expand employment opportunities available to Chambers College students in recognition of their academic performance and professional promise. Honorees will participate in paid student work that simultaneously allows them to gain real-world experience, connect with industry, and serve the state and people of West Virginia.

This generous investment from Rusty and Kimberly Hutson will allow us to greatly expand experiential learning opportunities to our business students, which is at the core of our purpose in the Chambers College as we move into Reynolds Hall in a few short months, said Josh Hall, Milan Puskar Dean. They will be market-ready and prepared to solve the business problems of the future because of the hands-on learning experiences this gift will provide, while also honoring our land-grant mission as a university and learning the importance of service to our state.

The Hutsons gift to support the West Virginia Faith Community Nursing Initiative will allow the School of Nursing to partner with nurses throughout the state to provide health screenings, education and more at community faith centers. The goal is to expand access to health care, particularly in the states most rural and economically challenged counties.

Meeting people where they are is an essential component of health care, said Tara Hulsey,dean of the School of Nursing and E. Jane Martin Endowed Professor. This generous gift from the Hutsons will help provide greater access to care in the areas that need it most.

The couples contribution to the Rockefeller Neuroscience Institute will enhance personalized patient care at the RNI. Expanded patient assistance will ensure a greater number of patients receive comprehensive, compassionate care in a coordinated fashion from their initial visit through all follow-up appointments, as well as any other resources and support necessary for patients and their families.

WethanktheHutsonsfor their gift,whichwillexpandour teamscapabilities toprovidea coordinated, personalized experienceandworld-classcare forpatientsand their families affectedby neurological and mental health conditions,said Dr. AliRezai, executive chair of the Rockefeller Neuroscience Institute.

Rusty and Kimberly Hutson were both raised in Harrison County and graduated from Fairmont State University, where they earned degrees in accounting and nursing, respectively. Rusty Hutson worked in the banking industry for 13 years before co-founding Diversified Energy in 2001. He now serves as CEO of the company, building upon a family history in the oil and natural gas business that dates to the early 1900s.

Kimberly Hutson worked as a registered nurse before becoming a full-time mom to the couples four children. While the Hutsons reside in Birmingham, Alabama, they remain committed to the Mountain State. They have previously provided generous support for WVU athletics and business and nursing programs at Fairmont State.

The Hutsons gift was made through the WVU Foundation, the nonprofit organization that receives and administers private donations on behalf of the University, in conjunction withWVU Day of Giving.Alumni and friends made over 5,600 gifts totaling $15.5 millionto support the Universitys fifthDay of Giving on March 9.

-WVU-

cr/05/04/22

CONTACT: Cassie RiceCommunications SpecialistWVU Foundation}304-554-0217; crice@wvuf.org

Call 1-855-WVU-NEWS for the latest West Virginia University news and information from WVUToday.

Follow @WVUToday on Twitter.

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WVU Today | WVU experiential business learning, health care outreach and personalized nursing bolstered by couple's $1.8M gift - WVU Today

Neuroscience

Gene Therapy Reverses Effects of Autism-Linked Mutation in Brain Organoids – Neuroscience News

Summary: A brain organoid study reveals how a genetic mutation associated with Pitt-Hopkins syndrome, a profound form of autism, disrupts neural development. Using gene-editing technology, researchers recovered the function of the TCF4 gene and effectively restored neural structure and function.

Source: UCSD

In a study published inNature Communications, scientists at University of California San Diego School of Medicine used human brain organoids to reveal how a genetic mutation associated with a profound form of autism disrupts neural development.

Using gene therapy tools to recover the genes function effectively rescued neural structure and function.

Several neurological and neuropsychiatric diseases, including autism spectrum disorders (ASD) and schizophrenia have been linked to mutations in Transcription Factor 4 (TCF4), an essential gene in brain development.

Transcription factors regulate when other genes are turned on or off, so their presence, or lack thereof, can have a domino effect in the developing embryo. Still, little is known about what happens to the human brain whenTCF4is mutated.

To explore this question, researchers focused on Pitt-Hopkins Syndrome, an ASD specifically caused by mutations inTCF4. Children with the genetic condition have profound cognitive and motor disabilities and are typically non-verbal.

Existing mouse models of Pitt-Hopkins Syndrome fail to accurately mimic patients neural characteristics, so the UC San Diego team instead created a human research model of the disorder. Using stem cell technology, they converted patients skin cells into stem cells, which were then developed into three-dimensional brain organoids, or mini-brains.

Initial observations of the brain organoids revealed a slew of structural and functional differences between theTCF4-mutated samples and their controls.

Even without a microscope, you could tell which brain organoid had the mutation, said senior study author Alysson R. Muotri, PhD, professor at UC San Diego School of Medicine, director of the UC San Diego Stem Cell Program and member of the Sanford Consortium for Regenerative Medicine.

TheTCF4-mutated organoids were substantially smaller than normal organoids, and many of the cells were not actually neurons, but neural progenitors. These simple cells are meant to multiply and then mature into specialized brain cells, but in the mutated organoids, some part of this process had gone awry.

A series of experiments revealed that theTCF4mutation led to downstream dysregulation ofSOXgenes and the Wnt pathway, two important molecular signals that guide embryonic cells to multiply, mature into neurons and migrate to the correct location in the brain.

Due to this dysregulation, neural progenitors did not multiply efficiently and thus fewer cortical neurons were produced. The cells that did mature into neurons were less excitable than normal and often remained clustered together instead of arranging themselves into finely-tuned neural circuits.

This atypical cellular architecture disrupted the flow of neural activity in the mutated brain organoid, which authors said would likely contribute to impaired cognitive and motor function down the line.

We were surprised to see such major developmental issues at all these different scales, and it left us wondering what we could do to address them, said first author Fabio Papes, PhD, associate professor at the University of Campinas and visiting scholar at UC San Diego School of Medicine, who jointly supervised the work with Muotri. Papes has a relative with Pitt-Hopkins Syndrome, which motivated him to studyTCF4.

The team tested two different gene therapy strategies for recovering the functional gene in brain tissue. Both methods effectively increasedTCF4levels, and in doing so, corrected Pitt-Hopkins Syndrome phenotypes at molecular, cellular and electrophysiological scales.

The fact that we can correct this one gene and the entire neural system reestablishes itself, even at a functional level, is amazing, said Muotri.

Muotri notes that these genetic interventions took place at a prenatal stage of brain development, whereas in a clinical setting, children would receive their diagnosis and treatment a few years later. Thus, clinical trials must first confirm whether a later intervention is still safe and effective.

The team is currently optimizing their recently licensed gene therapy tools in preparation for such a trial, in which spinal injections of the genetic vector would hopefully recover TCF4 function in the brain.

For these children and their loved ones, any improvements in motor-cognitive function and quality of life would be worth the try, Muotri said.

What is truly outstanding about this work is that these researchers are going beyond the lab and working hard to make these findings translatable to the clinic, said Audrey Davidow, president of the Pitt Hopkins Research Foundation. This is so much more than a stellar academic paper; its a true measure of what well-practiced science can accomplish to hopefully change human lives for the better.

Co-authors include: Janaina S. de Souza, Ryan A. Szeto, Erin LaMontagne, Simoni H. Avansini, Sandra M. Sanchez-Sanchez, Wei Wu, Hang Yao and Gabriel Haddad at UC San Diego; Antonio P. Camargo, Vinicius M. A. Carvalho, Jose R. Teixeira, Thiago S. Nakahara, Carolina N. Santo, Barbara M. P. Araujo and Paulo E. N. F. Velho at the University of Campinas.

Author: Nicole MlynarykSource: UCSDContact: Nicole Mlynaryk UCSDImage: The image is credited to UCSD

Original Research: Open access.Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content by Alysson R. Muotri et al. Nature Communications

Abstract

Transcription Factor 4 loss-of-function is associated with deficits in progenitor proliferation and cortical neuron content

Transcription Factor 4 (TCF4)has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathologicalTCF4mutations affect the human neural tissue is poorly understood.

Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations inTCF4.

We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons.

We identify a mechanism through whichTCF4loss-of-function leads to decreased Wnt signaling and then to diminished expression ofSOXgenes, culminating in reduced progenitor proliferation in vitro.

Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction ofTCF4expression or by pharmacological modulation of Wnt signaling.

This work delineates pathological mechanisms in neural cells harboringTCF4mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.

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Gene Therapy Reverses Effects of Autism-Linked Mutation in Brain Organoids - Neuroscience News

Neuroscience

WEIZMANN INSTITUTE OF SCIENCE CELEBRATES A TRANSFORMATIVE GIFT FROM THE MIKE AND VALERIA ROSENBLOOM FOUNDATION TO ADVANCE POSITIVE NEUROSCIENCE -…

Focused on how the brain enriches our lives, the investment will establish the Mike and Valeria Rosenbloom Center for Research on Positive Neuroscience

Mike and Valeria Rosenbloom

Valeria Rosenbloom and her late husband Mike Rosenbloom (zl)

Montreal, QC, May 03, 2022 (GLOBE NEWSWIRE) -- FOR IMMEDIATE RELEASE - WEIZMANN INSTITUTE OF SCIENCE CELEBRATES A TRANSFORMATIVE GIFT FROM THE MIKE AND VALERIA ROSENBLOOM FOUNDATION TO ADVANCE POSITIVE NEUROSCIENCE

MONTREAL, QC (May 3, 2022) Weizmann Canada is thrilled to announce a visionary gift from Valeria Rosenbloom of Montreal, enabling the establishment of the Mike and Valeria Rosenbloom Center for Research on Positive Neuroscience. This center is one of 12 within the flagship Azrieli Institute for Brain and Neural Sciences, at the globally-renowned Weizmann Institute of Science in Israel.

Positive neuroscience is an emerging field globally, forging new paths of discovery in brain health through human flourishing and well-being, building on the more conventional exploration of diminishing health through illness and disease, said Weizmann Institute President, Prof. Alon Chen. We are grateful to the Mike and Valeria Rosenbloom Foundation for its generous contribution that will enable this new center to work alongside and in collaboration with 11 other centers, in order to tackle the enormous task of answering the most complex questions in the field of neuroscience.

The Rosenbloom leadership investment, inspired by a keen desire to focus on prevention, will help bolster this emerging field.

The curiosity-driven research that is the fundamental essence of the Weizmann Institute is perfectly aligned with what I believe and what Mike also believed that this will lead to more discoveries, said Valeria Rosenbloom. Nutrition, lifestyle, clean water, air pollution, sunlight, sleep, social interaction and many other elements have an impact on our brains and our overall health, and I am very proud that this new center will help us to get a better understanding of why.

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Treasured friends of the Weizmann Institute, Valeria and her late husband Mikes (zl) support for cancer and neuroscience research, as well as scholarships, has had a tremendous impact on both Weizmann scientists and students.

We are incredibly grateful for Valeria Rosenblooms generosity in supporting this vital initiative, said Susan Stern, CEO of Weizmann Canada. Valerias leadership through this investment will benefit humankind by focusing on what our brains truly do well, to help enrich our lives for every day that we spend on this precious Earth. We are so proud that the Rosenbloom name will forever be synonymous with this crucial area of well-being.

Under the leadership of Prof. Yaniv Ziv of the Department of Brain Sciences, the Mike and Valeria Rosenbloom Center for Research on Positive Neuroscience will launch investigations into human resilience to the stresses of modern life, individual differences in how we overcome trauma, injury, and age-related deficits, and the most outstanding examples of human intelligence and social collaboration.

While mental resilience to chronic stress is a topic of perennial importance, it feels especially pertinent right now, as people worldwide have been forced to cope with isolation and restrictions on movement due to the pandemic. Incidentally, Canadian Mental Health Week (May 2-8), focuses on the importance of empathy as the pandemic persists. The compassionate brain is a crucial and natural part of being human, and an example of a novel area of research being done in positive neuroscience.

The Rosenbloom Center will also support studies on how to harness what is learned about the brain to improve teaching and educational strategies.

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Additional resources

For more information please contact:

ABOUT WEIZMANN CANADA

Since 1964, Weizmann Canada has partnered with individuals, families, foundations, and the business community to develop funding for the Weizmann Institute of Science; sharing the Institutes research with the Canadian public; and promoting science literacy and educational programs across all age groups. From coast to coast, Weizmann Canada hosts meetings and interactive events with Weizmann Institute Scientists; provides opportunities for participation in educational programs for high school students and young adults; and brings Canadians a front row seat to research that has and will continue to change the world. weizmann.ca

ABOUT THE WEIZMANN INSTITUTE OF SCIENCE

The Weizmann Institute of Science, located in Israel is one of the worlds leading multidisciplinary institutions of basic research. Weizmann Institute scientists have made a global impact in a variety of areas ranging from health and medicine to alternative energy and security and technology. Our specific impact includes being credited for inventing amniocentesis, developing a block buster drug for multiple sclerosis, and developing encryption technology to power internet and smart cards. weizmann.ac.il

ABOUT THE MIKE AND VALERIA ROSENBLOOM FOUNDATION

Valeria Rosenbloom, together with her late husband Mike, established The Mike & Valeria Rosenbloom Foundation. Mike Rosenbloom, founded Globe Communications Corp., an international publishing company and together, through their Foundation, the couple supported their interests in medical research and Israel. The Mike & Valeria Rosenbloom Foundation has supported several initiatives at the Weizmann Institute of Science, including the Israel National Postdoctoral Award Program for Advancing Women in Science, research on autism, Alzheimers, and the research of Prof. Zvi Livneh on cancer prevention.

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Neuroscience

Infants Preferentially Perceive Faces in the Upper Visual Field – Neuroscience News

Summary: The upper visual field bias for faces emerges at around 7 months of age. Babies over 7 months developed a preference for memorizing the upper portions of a face.

Source: Chuo University

It has previously been reported that the human visual system has an asymmetry in the visual field. For example, humans are better at finding faces in the upper visual field than lower visual field (called upper visual field bias for faces).

The underlying mechanisms of this visual field bias are subject to much debate, but a recent infant study suggests that the visual experience in daily life contribute to the emergence of upper visual field bias for faces.

In this study from Chuo University, Japan Womens University, and Hokkaido University, infants aged 5 to 8 months were presented with two face images vertically or horizontally.

Researchers tested which face they first looked at, and found that infants aged over 7 months first looked at the top face more frequently while infants aged under 6 months equally looked at both faces. There was no difference in horizontal meridian regardless of ages.

This result suggests that the upper visual field bias for faces emerges around 7 months.

This bias is specific to faces: the infants were also presented with images of houses, but no bias was observed. This indicates that is the face is important factor inducing the visual field bias.

Furthermore, infants aged over 7 months preferentially memorized the top face even when they spent an equal amount of time viewing two face images.

These results suggest that there is a developmental change in the upper visual field bias for faces between the ages of 6 and 7 months, implying that experience with faces in daily life is related to the emergence of upper visual field bias for faces.

Throughout the development, what infants see in daily life changes. The experience with the spatial relationship between the face and body (that the face is attached to the body) is accumulated during the development. We assume that the proportion of viewing face and body relationship leads to the upper visual field bias for faces, said Shuma Tsurumi from Chuo University.

Interestingly, we also found that infants prioritize to remember the top face, said Jun Kawahara from Hokkaido University.

This bias could be a basis for our indispensable drive to find people to communicate and interact with others.

This is a joint release by Chuo University and Hokkaido University.

Funding: The study, published inDevelopmental Science, was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) Fellows (19J21422), a Grant-in-Aid for Scientific Research on Innovative Areas, Construction of the FaceBody Studies in Transcultural Conditions (17H06343), from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), and a Grant-in-Aid for Scientific Research (B) from the JSPS (19H01774).

Author: Yoshi NoguchiSource: Chuo UniversityContact: Yoshi Noguchi Chuo UniversityImage: The image is credited to Chuo University, LAIMAN

Original Research: Closed access.Development of upper visual field bias for faces in infants by Shuma Tsurumi et al. Developmental Science

Abstract

Development of upper visual field bias for faces in infants

The spatial location of the face and body seen in daily life influences human perception and recognition. This contextual effect of spatial locations suggests that daily experience affects how humans visually process the face and body. However, it remains unclear whether this effect is caused by experience, or innate neural pathways.

To address this issue, we examined the development of visual field asymmetry for face processing, in which faces in the upper visual field were processed preferentially compared to the lower visual field. We found that a developmental change occurred between 6 and 7 months.

Older infants aged 78 months showed bias toward faces in the upper visual field, similar to adults, but younger infants of 56 months showed no such visual field bias. Furthermore, older infants preferentially memorized faces in the upper visual field, rather than in the lower visual field.

These results suggest that visual field asymmetry is acquired through development, and might be caused by the learning of spatial location in daily experience.

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Neuroscience

BioXcel Therapeutics to Present at Three Upcoming Investor Conferences – Yahoo Finance

BioXcel Therapeutics

NEW HAVEN, Conn., May 05, 2022 (GLOBE NEWSWIRE) -- BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a commercial-stage biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology, today announced that Vimal Mehta, Ph.D., Founder and Chief Executive Officer, will participate in three upcoming investor conferences. Dr. Mehta will highlight the Companys neuroscience and immuno-oncology programs as well as its artificial intelligence platform used to augment and accelerate the drug candidate discovery and development process. He will also discuss the Companys commercial and launch readiness plans for IGALMI (dexmedetomidine) sublingual film.

Presentation Details:

Event: BofA Securities 2022 Healthcare Conference*Date: Thursday, May 12, 2022Time: 11:00 AM ET / 8:00 AM PT

Event: UBS Global Healthcare Conference 2022*Date: Monday, May 23, 2022Time: 10:00 AM ET

Event: H.C. Wainwright Global Investment ConferenceDate: Wednesday, May 25, 2022Time: 3:00 PM ET

To access live webcasts of the fireside chats and presentation, and any accompanying presentation materials, please visit "News/Events" within the Investors & Media section of the Companys website at http://www.bioxceltherapeutics.com beginning 15 minutes prior to the start time of the presentation. A replay of the webcast will be available on the Companys website following the event.

*Fireside chat format

About BioXcel Therapeutics, Inc.BioXcel Therapeutics, Inc. is a commercial-stage biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology. The Companys drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indices. The Companys commercial product, IGALMI (developed as BXCL501) is a proprietary, sublingual film formulation of dexmedetomidine approved by the FDA for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. The safety and effectiveness of IGALMI has not been established beyond 24 hours from the first dose. BXCL501 is also being evaluated for the acute treatment of agitation associated with Alzheimers disease, and as an adjunctive treatment for major depressive disorder. The Company is also developing BXCL502 as a potential therapy for chronic agitation in dementia and, under its subsidiary OnkosXcel Therapeutics, BXCL701, an investigational, orally administered, systemic innate immunity activator for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment nave to checkpoint inhibitors. For more information, please visit http://www.bioxceltherapeutics.com.

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Forward-Looking StatementsThis press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include but are not limited to the date, time and content of the Companys presentations at the BofA Securities 2022 Healthcare Conference, the UBS Global Healthcare Conference 2022, and the H.C. Wainwright Global Investment Conference. When used herein, words including anticipate, will, plan, may, continue, intend, designed, goal and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon the Companys current expectations and various assumptions. The Company believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. The Company may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, the important factors discussed under the caption Risk Factors in its Annual Report on Form 10-K for the year ended December 31, 2021, as such factors may be updated from time to time in its other filings with the SEC, which are accessible on the SECs website at http://www.sec.gov. These and other important factors could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, except as required by law, it disclaims any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing the Companys views as of any date subsequent to the date of this press release.

Contact Information

Corporate

BioXcel TherapeuticsErik Kopp1.203.494.7062ekopp@bioxceltherapeutics.com

Investor Relations

FTI ConsultingMatt Ventimiglia1.212.850.5624matthew.ventimiglia@fticonsulting.com

Media

FTI Consulting Helen OGorman1.718.408.0800helen.ogorman@fticonsulting.com

Source: BioXcel Therapeutics, Inc.

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BioXcel Therapeutics to Present at Three Upcoming Investor Conferences - Yahoo Finance

Neuroscience

Cognitive Impairment From Severe COVID-19 Equivalent to 20 Years of Aging – Neuroscience News

Summary: Severe COVID-19 infection results in cognitive impairment similar to that sustained by natural aging between the ages of 50 to 70, and is equivalent to losing 10 IQ points.

Source: University of Cambridge

Cognitive impairment as a result of severe COVID-19 is similar to that sustained between 50 and 70 years of age and is the equivalent to losing 10 IQ points, say a team of scientists from the University of Cambridge and Imperial College London.

The findings, published in the journaleClinicalMedicine, emerge from theNIHR COVID-19 BioResource. The results of the study suggest the effects are still detectable more than six months after the acute illness, and that any recovery is at best gradual.

There is growing evidence that COVID-19 can cause lasting cognitive and mental health problems, with recovered patients reporting symptoms including fatigue, brain fog, problems recalling words, sleep disturbances, anxiety and even post-traumatic stress disorder (PTSD) months after infection. In the UK, a study found that around one in seven individuals surveyed reported having symptoms that included cognitive difficulties 12 weeks after a positive COVID-19 test.

Whileeven mild cases can lead to persistent cognitive symptoms, between a third and three-quarters of hospitalised patients report still suffering cognitive symptoms three to six months later.

To explore this link in greater detail, researchers analysed data from 46 individuals who received in-hospital care, on the ward or intensive care unit, for COVID-19 at Addenbrookes Hospital, part of Cambridge University Hospitals NHS Foundation Trust. 16 patients were put on mechanical ventilation during their stay in hospital. All the patients were admitted between March and July 2020 and were recruited to the NIHR COVID-19 BioResource.

The individuals underwent detailed computerised cognitive tests an average of six months after their acute illness using the Cognitron platform, which measures different aspects of mental faculties such as memory, attention and reasoning. Scales measuring anxiety, depression and post-traumatic stress disorder were also assessed. Their data were compared against matched controls.

This is the first time that such rigorous assessment and comparison has been carried out in relation to the after effects of severe COVID-19.

COVID-19 survivors were less accurate and with slower response times than the matched control population and these deficits were still detectable when the patients were following up six months later.

The effects were strongest for those who required mechanical ventilation. By comparing the patients to 66,008 members of the general public, the researchers estimate that the magnitude of cognitive loss is similar on average to that sustained with 20 years aging, between 50 and 70 years of age, and that this is equivalent to losing 10 IQ points.

Survivors scored particularly poorly on tasks such as verbal analogical reasoning, a finding that supports the commonly-reported problem of difficulty finding words. They also showed slower processing speeds, which aligns with previous observations post COVID-19 of decreased brain glucose consumption within the frontoparietal network of the brain, responsible for attention, complex problem-solving and working memory, among other functions.

Professor David Menon from the Division of Anaesthesia at the University of Cambridge, the studys senior author, said: Cognitive impairment is common to a wide range of neurological disorders, including dementia, and even routine aging, but the patterns we saw the cognitive fingerprint of COVID-19 was distinct from all of these.

While it is now well established that people who have recovered from severe COVID-19 illness can have a broad spectrum of symptoms of poor mental health depression, anxiety, post-traumatic stress, low motivation, fatigue, low mood, and disturbed sleep the team found that acute illness severity was better at predicting the cognitive deficits.

The patients scores and reaction times began to improve over time, but the researchers say that any recovery in cognitive faculties was at best gradual and likely to be influenced by a number of factors including illness severity and its neurological or psychological impacts.

Professor Menon added: We followed some patients up as late as ten months after their acute infection, so were able to see a very slow improvement. While this was not statistically significant, it is at least heading in the right direction, but it is very possible that some of these individuals will never fully recover.

There are several factors that could cause the cognitive deficits, say the researchers.Direct viral infection is possible, but unlikely to be a major cause; instead, it is more likely that a combination of factors contribute, including inadequate oxygen or blood supply to the brain, blockage of large or small blood vessels due to clotting, and microscopic bleeds. However, emerging evidence suggests that the most important mechanism may be damage caused by the bodys own inflammatory response and immune system.

While this study looked at hospitalised cases, the team say that even those patients not sick enough to be admitted may also have tell-tale signs of mild impairment.

Professor Adam Hampshire from the Department of Brain Sciences at Imperial College London, the studys first author, said: Around 40,000 people have been through intensive care with COVID-19 in England alone and many more will have been very sick, but not admitted to hospital. This means there is a large number of people out there still experiencing problems with cognition many months later. We urgently need to look at what can be done to help these people.

Professor Menon and Professor Ed Bullmore from Cambridges Department of Psychiatry are co-leading working groups as part of theCOVID-19 Clinical Neuroscience Study (COVID-CNS)that aim to identify biomarkers that relate to neurological impairments as a result of COVID-19, and the neuroimaging changes that are associated with these.

Funding: The research was funded by the NIHR BioResource, NIHR Cambridge Biomedical Research Centre and the Addenbrookes Charitable Trust.

Author: Craig BrierleySource: University of CambridgeContact: Craig Brierley University of CambridgeImage: The image is in the public domain

Original Research: Open access.Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort by Hampshire, A et al. eClinicalMedicine

Abstract

Multivariate profile and acute-phase correlates of cognitive deficits in a COVID-19 hospitalised cohort

Preliminary evidence has highlighted a possible association between severe COVID-19 and persistentcognitive deficits. Further research is required to confirm this association, determine whether cognitive deficits relate to clinical features from the acute phase or to mental health status at the point of assessment, and quantify rate of recovery.

46 individuals who received critical care for COVID-19 at Addenbrookes hospital between 10th March 2020 and 31st July 2020 (16 mechanically ventilated) underwent detailed computerised cognitive assessment alongside scales measuring anxiety, depression and post-traumatic stress disorder under supervised conditions at a mean follow up of 6.0 ( 2.1) months following acute illness.

Patient and matched control (N=460) performances were transformed into standard deviation from expected scores, accounting for age and demographic factors usingN=66,008 normative datasets. Global accuracy and response time composites were calculated (G_SScore & G_RT). Linear modelling predicted composite score deficits from acute severity, mental-health status at assessment, and time from hospital admission.

The pattern of deficits across tasks was qualitatively compared with normal age-related decline, and early-stagedementia.

COVID-19 survivors were less accurate (G_SScore=-0.53SDs) and slower (G_RT=+0.89SDs) in their responses than expected compared to their matched controls. Acute illness, but not chronic mental health, significantly predicted cognitive deviation from expected scores (G_SScore (p=0.0037) and G_RT (p=0.0366)).

The most prominent task associations with COVID-19 were for higher cognition and processing speed, which was qualitatively distinct from the profiles of normal aging and dementia and similar in magnitude to the effects of aging between 50 and 70 years of age. A trend towards reduced deficits with time from illness (r=0.15) did not reach statistical significance.

Cognitive deficits after severe COVID-19 relate most strongly to acute illness severity, persist long into the chronic phase, and recover slowly if at all, with a characteristic profile highlighting higher cognitive functions and processing speed.

This work was funded by theNational Institute for Health Research(NIHR) CambridgeBiomedical ResearchCentre (BRC), NIHR Cambridge Clinical Research Facility (BRC-1215-20014), the Addenbrookes Charities Trust and NIHR COVID-19 BioResource RG9402. AH is funded by theUKDementia Research Institute Care Research and Technology Centre and Imperial College London Biomedical Research Centre. ETB and DKM are supported byNIHRSenior Investigator awards.JBR is supported by theWellcome Trust(220258) and Medical Research Council (SUAG/051 G101400). VFJN is funded by an Academy of Medical Sciences/ The Health Foundation Clinician Scientist Fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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Neuroscience

Biogen and MedRhythms to Develop and Commercialize a Prescription Digital Therapeutic Targeting the Treatment of Gait Deficits in Multiple Sclerosis -…

Biogen Inc.

The investigational prescription digital therapeutic uses a combination of sensors, software, and music based on Rhythmic Auditory Stimulation (RAS)

MedRhythms to receive a $3 million upfront payment as part of the agreement and is eligible to receive potential development and commercial milestone payments

CAMBRIDGE, Mass. and PORTLAND, Maine, May 05, 2022 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) and MedRhythms have entered into a license agreement to develop and commercialize MR-004, an investigational prescription digital therapeutic for the potential treatment of gait deficits in multiple sclerosis (MS). The collaboration combines MedRhythms digital expertise with Biogens leadership and global footprint in MS in order to address significant unmet patient needs.

MedRhythms is developing next-generation prescription digital therapeutics across a broad range of indications in neurology via a technology platform that leverages advancements in neuroscience and music to target improved walking and mobility. MR-004 is MedRhythms pipeline candidate in MS, which aims to improve gait and gait-related aspects of movement, potentially providing MS patients with improved independence related to mobility. If approved, MR-004 has the potential to become the first prescription digital therapeutic for gait deficit in MS. MedRhythms is currently conducting two ongoing feasibility studies for MR-004, and, based on the readout of the first study, plans to initiate a registrational trial in the near future.

As part of our aspiration in digital health, together with MedRhythms we aim to advance a new, innovative treatment option for people living with MS that may help address walking impairment, a common issue that impacts their overall quality of life, said Martin Dubuc, Head of Biogen Digital Health. Pioneering in digital therapeutics exemplifies Biogens commitment to advance novel therapies that we hope will improve outcomes for people living with MS.

At MedRhythms, we are committed to redefining what is possible for people living with neurologic diseases by building evidence-based products that meaningfully impact symptoms that have been underserved by traditional treatment modalities, said Brian Harris, Chief Executive Officer of MedRhythms. We look forward to what our collaboration with Biogen, a global leader in MS, could mean for the patients we serve around the world.

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Under the terms of the agreement, Biogen will make an upfront payment of $3 million to MedRhythms. Should certain development and commercial milestones be achieved, MedRhythms will be eligible to receive up to $117.5 million in potential milestone payments. MedRhythms is also eligible to receive tiered royalties in the high-single digits to low-teens on potential global sales.

About BiogenAs pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the worlds first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and is providing the first and only approved treatment to address a defining pathology of Alzheimers disease. Biogen is also commercializing biosimilars and focusing on advancing the industrys most diversified pipeline in neuroscience that will transform the standard of care for patients in several areas of high unmet need.

In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives aims to eliminate fossil fuels across the companys operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.

The company routinely posts information that may be important to investors on its website at http://www.biogen.com. To learn more, please visit http://www.biogen.com and follow Biogen on social media Twitter, LinkedIn, Facebook, YouTube.

About MedRhythmsMedRhythms is pioneering the development of next-generation therapeutics designed to improve walking and functional outcomes via a proprietary, patented platform that combines sensors, software, and music with advanced neuroscience. The company is developing a pipeline of evidence-based digital therapeutics in neurological conditions, such as stroke, multiple sclerosis and Parkinsons disease, that target neural circuitry. The companys pipeline product for chronic stroke walking deficits received Breakthrough Device designation in 2020 and the company raised a Series B financing round in 2021 led by Morningside Ventures and Advantage Capital. MedRhythms is headquartered in Portland, Maine. For more information, visit http://www.medrhythms.com.

Biogen Safe Harbor This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, the potential benefits of MR-004; the potential benefits and results that may be achieved through our collaboration with MedRhythms; the potential of our commercial business and pipeline programs; and our strategy and plans. These statements may be identified by words such as aim, anticipate, believe, could, estimate, expect, forecast, goal, intend, may, plan, possible, potential, will, would and other words and terms of similar meaning. You should not place undue reliance on these statements, or the scientific data presented.

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, the risks of unexpected costs or delays; the risk of other unexpected hurdles; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; regulatory authorities may require additional information or further studies; third party collaboration risks; and the direct and indirect impacts of the ongoing COVID-19 pandemic on our business, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise.

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Biogen and MedRhythms to Develop and Commercialize a Prescription Digital Therapeutic Targeting the Treatment of Gait Deficits in Multiple Sclerosis -...

Neuroscience

A very specific kind of brain cell dies off in people with Parkinson’s – Science News Magazine

Deep in the human brain, a very specific kind of cell dies during Parkinsons disease.

For the first time, researchers have sorted large numbers of human brain cells in the substantia nigra into 10 distinct types. Just one is especially vulnerable in Parkinsons disease, the team reports May 5 in Nature Neuroscience. The result could lead to a clearer view of how Parkinsons takes hold, and perhaps even ways to stop it.

The new research goes right to the core of the matter, says neuroscientist Raj Awatramani of Northwestern University Feinberg School of Medicine in Chicago. Pinpointing the brain cells that seem to be especially susceptible to the devastating disease is the strength of this paper, says Awatramani, who was not involved in the study.

Parkinsons disease steals peoples ability to move smoothly, leaving balance problems, tremors and rigidity. In the United States, nearly 1 million people are estimated to have Parkinsons. Scientists have known for decades that these symptoms come with the death of nerve cells in the substantia nigra. Neurons there churn out dopamine, a chemical signal involved in movement, among other jobs (SN: 9/7/17).

But those dopamine-making neurons are not all equally vulnerable in Parkinsons, it turns out.

This seemed like an opportunity to really clarify which kinds of cells are actually dying in Parkinsons disease, says Evan Macosko, a psychiatrist and neuroscientist at Massachusetts General Hospital in Boston and the Broad Institute of MIT and Harvard.

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The tricky part was that dopamine-making neurons in the substantia nigra are rare. In samples of postmortem brains, we couldnt survey enough of [the cells] to really get an answer, Macosko says. But Abdulraouf Abdulraouf, a researcher in Macoskos laboratory, led experiments that sorted these cells, figuring out a way to selectively pull the cells nuclei out from the rest of the cells present in the substantia nigra. That enrichment ultimately led to an abundance of nuclei to analyze.

By studying over 15,000 nuclei from the brains of eight formerly healthy people, the researchers further sorted dopamine-making cells in the substantia nigra into 10 distinct groups. Each of these cell groups was defined by a specific brain location and certain combinations of genes that were active.

When the researchers looked at substantia nigra neurons in the brains of people who died with either Parkinsons disease or the related Lewy body dementia, the team noticed something curious: One of these 10 cell types was drastically diminished.

These missing neurons were identified by their location in the lower part of the substantia nigra and an active AGTR1 gene, lab member Tushar Kamath and colleagues found. That gene was thought to serve simply as a good way to identify these cells, Macosko says; researchers dont know whether the gene has a role in these dopamine-making cells fate in people.

The new finding points to ways to perhaps counter the debilitating diseases. Scientists have been keen to replace the missing dopamine-making neurons in the brains of people with Parkinsons. The new study shows what those cells would need to look like, Awatramani says. If a particular subtype is more vulnerable in Parkinsons disease, maybe thats the one we should be trying to replace, he says.

In fact, Macosko says that stem cell scientists have already been in contact, eager to make these specific cells. We hope this is a guidepost, Macosko says.

The new study involved only a small number of human brains. Going forward, Macosko and his colleagues hope to study more brains, and more parts of those brains. We were able to get some pretty interesting insights with a relatively small number of people, he says. When we get to larger numbers of people with other kinds of diseases, I think were going to learn a lot.

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Anatomy

Jesse Williams and Sarah Drew to Appear on Greys Anatomy Season Finale – Variety

The once-and-future Greys Anatomy super couple of Jackson and April played by Jesse Williams and Sarah Drew are set to appear on the finale of the medical dramas 18th season on May 26, Variety has confirmed.

Williams left Greys Anatomy last season, having played Jackson since the shows sixth season. Drew, whod departed the show in 2018, returned for a guest appearance in May 2021 to send Jackson off to his new life in Boston, where he was taking over his familys foundation. April ended up moving there with him, having ended her relationship with her husband.

The onscreen pair share a daughter, and their portmanteau is Japril and though Japril fans would love a spinoff show revolving around the two characters, an ABC spokesperson batted down that idea to Variety on Friday. Nor could ABC offer any other details about the context in which Jackson and April will appear on the finale episode.

Upon his departure last year, Williams told Deadline that hed be happy to return to the show as a guest star. Williams is currently starring on Broadway in Take Me Out. Varietys review this month called his performance impressive as the embodiment of charisma and cool, in the role of Darren, whose coming out the play revolves around.

When Williams left Greys Anatomy, he thanked its creator, Shonda Rhimes, showrunner Krista Vernoff, star Ellen Pompeo and executive producer Debbie Allen, who also plays Catherine Avery, Jacksons mother. In a statement toVarietythen, he said, As an actor, director and person, I have been obscenely lucky to learn so much from so many and I thank our beautiful fans, who breathe so much energy and appreciation into our shared worlds. The experience and endurance born of creating nearly 300 hours of leading global television is a gift Ill carry always. I am immensely proud of our work, our impact and to be moving forward with so many tools, opportunities, allies and dear friends.

Deadline was the first to report the news of Williams and Drews return.

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Jesse Williams and Sarah Drew to Appear on Greys Anatomy Season Finale - Variety