BIORESTORATIVE THERAPIES, INC. (OTCMKTS:BRTX) Files An 8-K Submission of Matters to a Vote of Security Holders – Market Exclusive

BIORESTORATIVE THERAPIES, INC. (OTCMKTS:BRTX) Files An 8-K Submission of Matters to a Vote of Security HoldersItem 5.07 Submission of Matters to a Vote of Security Holders.

On November 13, 2019, BioRestorative Therapies, Inc. (the Company) held a Special Meeting of Stockholders (the Special Meeting). The following is a listing of the votes cast for and against, as well as abstentions, with respect to the matters voted upon at the Special Meeting. At the Special Meeting, the Companys stockholders (i) approved an amendment to the Companys Certificate of Incorporation to increase the number of shares of common stock authorized to be issued by the Company from 150,000,000 to 300,000,000, (ii) approved amendments to the Certificate of Incorporation of the Company, and authorized the Board of Directors of the Company to select and file one such amendment, to effect a reverse stock split of the Companys common stock at a ratio of not less than 1-for-2 and not more than 1-for-100, with the Board of Directors of the Company having the discretion as to whether or not the reverse stock split is to be effected, and with the exact ratio of any reverse stock split to be set at a whole number within the above range as determined by the Companys Board of Directors in its discretion (the Reverse Stock Split Proposal), which Reverse Stock Split Proposal revises the reverse stock split ratio approved by the Companys stockholders on May 30, 2019 and (iii) authorized the Board of Directors of the Company, in its discretion, to reduce the number of shares of common stock authorized to be issued by the Company in proportion to the percentage decrease in the number of outstanding shares of common stock resulting from the reverse split (or a lesser decrease in authorized shares of common stock as determined by the Companys Board of Directors in its discretion).

(d) Exhibits.

3.1 Certificate of Amendment of Certificate of Incorporation of the Company

About BIORESTORATIVE THERAPIES, INC. (OTCMKTS:BRTX)

BioRestorative Therapies, Inc. develops therapeutic products and medical therapies using cell and tissue protocols, involving adult (non-embryonic) stem cells. The Company offers human and plant stem cell derived cosmetic and skin care products. Its programs relate to the treatment of disc/spine disease and metabolic disorders and include Disc/Spine Program (brtxDISC) and Metabolic Program (ThermoStem). Its curved needle device (CND) is a needle system with a curved inner cannula to allow access to difficult-to-locate regions for the delivery or removal of fluids and other substances. The CND is intended to deliver stem cells and/or other therapeutic products or material to the interior of a human intervertebral disc, the spine region, or other areas of the body. The device relies on the use of pre-curved nested cannulae that allows the cells or material to be deposited in the posterior and lateral aspects of the disc to which direct access is not possible due to outlying structures.

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BIORESTORATIVE THERAPIES, INC. (OTCMKTS:BRTX) Files An 8-K Submission of Matters to a Vote of Security Holders - Market Exclusive

Global Cell Expansion Market 2019 is predicted to reach an excellent valuation of by 2024 – Galus Australis

According to this Cell Expansion report, the key market players are making moves like product launches, joint ventures, developments, mergers and acquisitions which has influence on the market and healthcare Industry as a whole and also affecting the sales, import, export, revenue and CAGR values.

With Cell Expansion Market report you can build a strong organization and make better decisions that take your business on the right track. This report is a valuable source of assistance for companies and individuals that offers industry chain structure, business strategies and proposals for new project investments. This report introduces top to bottom evaluation of the Healthcare industry including empowering technologies, key trends, market drivers, challenges, standardization, regulatory landscape, opportunities, future guide, value chain, ecosystem player profiles and strategies. This industry analysis report speaks in detail about the manufacturing process, type and applications.

Some of the eminent industry players operating in Cell Expansion Market are BD, Merck KGaA, TERUMO BCT, INC., Lonza, Beckman Coulter, Inc., Cyto-Matrix Inc., ReNeuron Group plc, pluristem, NexImmune, RepliCel, TC BioPharm, GE Healthcare, Thermo Fisher Scientific, Inc., Corning Incorporated, Miltenyi Biotec, STEMCELL Technologies Inc., Danaher, CellProthera and others

The Global Cell Expansion Market is accounted for USD 11.43 billion and market is growing at a CAGR of 17.8% by the end of 2024.

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Cell expansion which deals with the production of cells from single cell, is used in therapeutic development, drug screening, and microlevel research of cells. Recently, cell expansion is widely used for improving transplantation and in the treatment of various diseases including rheumatoid arthritis, diabetes, and others.

The increasing prevalence of chronic diseases combined with the increase in research activities are the main factors driving the market for cellular expansion. Furthermore, technological advances in cellular expansion devices and the growth of public healthcare investment are the factors driving the market for cellular expansion. Furthermore, it is expected that even economic tools for cell-based research will promote the market for cell expansion during the forecast period.

The global cell expansion market is highly fragmented and is based on new product launches and clinical results of products. Hence the major players have used various strategies such as new product launches, clinical trials, market initiatives, high expense on research and development, agreements, joint ventures, partnerships, acquisitions, and others to increase their footprints in this market. The report includes market shares of cell expansion market for global, Europe, North America, Asia Pacific and South America.

Key Segmentation of Global Cell Expansion Market

By product, global cell expansion market is segmented into

consumables and

instruments

Consumables are further sub segmented into reagents, media, & serum and disposables.

Disposables are again sub segmented into bioreactor accessories, tissue culture flasks and others.

Instruments are segmented into cell expansion supporting equipment, bioreactors and automated cell expansion systems.

Cell Expansion Supporting Equipment can be further sub segmented into flow cytometers, centrifuges, cell counters and others.

Bioreactors can be further sub segmented into perfusion bioreactors and microcarrier bioreactors.

Microcarrier Bioreactors can be sub segmented into anchorage-dependent and anchorage independent.

On the basis of application, global cell expansion market is segmented into

regenerative medicine,

stem cell research,

oncology and

cell-based research and others

On the basis of cell type, global cell expansion market is segmented into

human cells and

animal cells

Human cells can be further sub segmented into stem cells and differentiated cells. Stem cells are sub segmented into adult stem cells, embryonic stem cells and induced pluripotent stem cells.

Based on end user, global cell expansion market is segmented into

pharma & biotech companies,

research institutes,

cell banks and others

On the basis of geography, global cell expansion market report covers data points for 28 countries across multiple geographies such as

North America & South America,

Europe,

Asia-Pacific, and

Middle East & Africa

Some of the major countries covered in this report are U.S., Canada, Germany, France, U.K., Netherlands, Switzerland, Turkey, Russia, China, India, South Korea, Japan, Australia, Singapore, Saudi Arabia, South Africa, and Brazil among others. In 2017, North America is expected to dominate the market.

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Table of Contents: Global Cell Expansion Market

Major Highlights of TOC:

Chapter One: Cell Expansion Market Industry Overview

1.1 Cell Expansion Industry

1.1.1 Overview

1.1.2 Products of Major Companies

1.2 Cell Expansion Market Segment

1.2.1 Industry Chain

1.2.2 Consumer Distribution

1.3 Price & Cost Overview

Chapter Two: Cell Expansion Market Demand

2.1 Segment Overview

2.1.1 APPLICATION 1

2.1.2 APPLICATION 2

2.1.3 Other

2.2 Cell Expansion Market Size by Demand

2.3 Cell Expansion Market Forecast by Demand

Chapter Three: Cell Expansion Market by Type

3.1 By Type

3.1.1 TYPE 1

3.1.2 TYPE 2

3.2 Cell Expansion Market Size by Type

3.3 Cell Expansion Market Forecast by Type

Chapter Four: Major Region of Cell Expansion Market

4.1 Cell Expansion Sales

4.2 Cell Expansion Revenue & market share

Chapter Five: Major Companies List

Chapter Six: Conclusion

Get TOC at https://databridgemarketresearch.com/toc/?dbmr=global-cell-expansion-market

About Data Bridge Market Research:

An absolute way to forecast what future holds is to comprehend the trend today!

Data Bridge set forth itself as an unconventional and neoteric Market research and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best market opportunities and foster efficient information for your business to thrive in the market. Data Bridge endeavors to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process.

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Global Cell Expansion Market 2019 is predicted to reach an excellent valuation of by 2024 - Galus Australis

Hip osteoarthritis: 6 ways to treat it – Medical News Today

Osteoarthritis, sometimes called "wear and tear" arthritis, is a common degenerative condition. Doctors can treat osteoarthritis with medication and surgery. People can also manage their symptoms with different exercises and stretches.

Osteoarthritis is the most widespread form of arthritis. The Arthritis Foundation estimate that in excess of 30 million people in the United States have osteoarthritis.

Although osteoarthritis can occur in any joint, it commonly affects the weight-bearing joints, such as the knees and hips.

Read on to find out more about osteoarthritis of the hip. We discuss what causes the condition, how doctors diagnose it, and the different ways to treat it.

Treatments for osteoarthritis focus on reducing pain and improving mobility. Effective ways to treat osteoarthritis include the following:

Pain management is essential for people living with hip osteoarthritis. People can treat mild to moderate pain with over-the-counter pain relievers, such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).

People who have moderate to severe osteoarthritis may experience more intense pain. In such cases, prescription pain relief may be necessary.

Some people may require medications to help slow the progression of arthritis or reduce some of the symptoms. Examples of such drugs include:

Corticosteroids

Corticosteroids control inflammation by mimicking the effects of cortisol, a hormone that regulates the immune system.

People can take oral corticosteroid tablets. Doctors can also inject corticosteroids directly into the hip joint. However, corticosteroid injections offer only temporary pain relief. People will require additional injections going forward.

Hyaluronic acid injections

Another potential treatment for osteoarthritis is an injection of hyaluronic acid into the hip joint or another joint that osteoarthritis is affecting.

In 2019, the Food and Drug Administration (FDA) approved a hyaluronic acid injection for treating osteoarthritis of the knee.

Although some doctors have used the injection to treat osteoarthritis of the hip, the FDA has not yet approved it for this use.

Hyaluronic acid injections do not affect everyone in the same way. Some people do not experience any pain relief after receiving the injection. However, approximately 30% of people stay pain free for up to two years, according to the Arthritis Foundation.

Physical therapists are trained healthcare professionals who specialize in diagnosing and treating conditions that limit mobility. People with hip osteoarthritis may benefit from physical therapy sessions.

During the initial session, the therapist will assess the person's physical condition and any specific mobility problems they have. They will then devise a set of tailored exercises to help improve mobility.

The therapist teaches people how to perform each exercise so that they can safely continue their treatment at home. They may also recommend additional treatment options, such as braces, walkers, or hot and cold therapy.

Some people experience severe hip pain or stiffness that significantly affects their quality of life. These people may benefit from surgery.

There are two main surgical options for hip osteoarthritis:

Hip resurfacing

This procedure involves trimming or shaving away damaged bone on the femoral head. The femoral head is the upper end of the thigh bone, which sits inside the hip socket.

After removing the damaged bone, the surgeon covers the femoral head with metal. The surgeon also fits a metal cup inside the hip socket.

Total hip replacement

During this procedure, a surgeon replaces the entire hip joint, including the femoral head and the socket. In their place, the surgeon fits artificial components made of metal, plastic, or ceramic.

Each surgical option carries benefits and risks. A doctor will guide people through the available options before deciding on the best treatment to pursue.

Stem cells are cells that have the potential to develop into a range of different cell types. Researchers are currently looking into whether stem cell therapies could help to replace and regenerate damaged tissues within the human body.

Mesenchymal stem cells are stem cells that can develop into bone and cartilage, among other types of tissue. According to a 2018 review, mesenchymal stem cells could help to repair damaged cartilage and reduce inflammation in knee osteoarthritis.

However, stem cell therapy is not yet ready for use in clinical settings. Advances in gene editing techniques may help overcome many of the limitations currently facing stem cell therapy.

Exercises that may help manage symptoms of hip osteoarthritis include:

Stretching every day can also help to improve flexibility and relieve joint stiffness and pain. Consider the following stretches:

Sitting hip flexion

Sit-stand

Hip opener

Forward fold

People can also perform this stretch from a seated position:

Cartilage is a rubber-like tissue that covers the ends of the bones in the joints. Here, it acts as a cushion that prevents the end of one bone from rubbing against the end of an adjoining one. It also provides lubrication that allows the joint to move easily and painlessly.

In osteoarthritis, the cartilage inside the joints wears away, causing two or more bones to rub together. This process results in joint inflammation, swelling, and pain.

The risk of osteoarthritis increases with age. As people grow older, the cartilage cushions between their joints slowly deteriorate. The symptoms of discomfort and pain tend to worsen as the cartilage continues to break down.

To diagnose hip osteoarthritis, a doctor will take a person's medical history and carry out a physical examination of the joints. The doctor may also order the following diagnostic tests:

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Hip osteoarthritis: 6 ways to treat it - Medical News Today

Cocker spaniel with cancer to receive stem cells from mother living 4,000 miles away – Fox News

A 6-year-old cocker spaniel in California that was recently diagnosed with cancer is slated to receive stem cells from her mother living 4,000 miles away in the United Kingdom.

Coco the cocker spaniel gave birth to a litter of puppies six years ago. One of those puppies, Millie, was adopted by Serena and Andrew Lodge, who now live in San Francisco. They may live across the world from each other, but the mother and daughter will soon be reunited for the rare treatment, reported South West News Service, or SWNS, a British news agency.

CHEAPER MEDICATION FOR DOGS WITH SEPARATION ANXIETY NOW APPROVED, FDA SAYS

Coco, left, and daughter, Millie. (SWNS)

The transplant will occur at the North Carolina State Veterinary Hospital in Raleigh. The facility isreportedly one of only a few animal hospitals in the world to offer the treatment, which involves taking healthy stem cells from Cocos bone marrow and injecting them intoMillies.

"Serena and Andrew started chemo on Millie three months ago but they've been told the only chance they'll have of curing her is if they find a positive donor so she can have a transplant, said Cocos owner, Robert Alcock, 52. He arrived with Coco in North Carolina on Wednesday.

Millie while in an animal hospital. (SWNS)

"They contacted us, and we sent some blood samples for testing, along with samples from one of Coco's other pups, he added. They both came back positive but because Coco is Millie's mother the vet said she would be a better match."

"Coco will go into hospital on Sunday for the procedure and then the cells will be donated on Monday, he continued, noting the Lodges have paid for everything.

Robert Alcock and his cocker spaniel, Coco. (SWNS)

BLACK LAB GIVES BIRTH TO 13 PUPPIES, SHOCKS OWNERS: 'THEY WERE JUST FLYING OUT'

Coco is expected to make a full recovery following the procedure. However, there is only a 50 percent chance Millie will be cured even if the treatment is successful, according to SWNS.

Stem cell therapy for pets is costly, typically setting an owner back between $2,000 and $3,000, according to Pet WebMD.

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Cocker spaniel with cancer to receive stem cells from mother living 4,000 miles away - Fox News

Gracell Announces Five Presentations at the Annual Meeting of American Society of Hematology (ASH) – BioSpace

SHANGHAI and SUZHOU, China, Nov. 15, 2019 /PRNewswire/ --Gracell Biotechnologies Co., Ltd. ("Gracell"), a clinical-stage immune cell therapy company, today announced five presentations to be delivered at the upcoming American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, held from December 7-10.

The presentations centre on Gracell's breakthrough FasTCARtechnology, and other two platform technology in four product categories used in the treatment of hematological malignancies, each with well-defined objectives, including:

The four product candidates are currently being studied in ongoing phase I clinical trials conducted by Gracell, Hebei Yanda Lu Daopei Hospital, and Xinqiao Hospital of AMU, and six other hospitals nationwide in China.

"These clinical studies demonstrated Gracell's product development strategy and strong capabilities to bring multiple novel therapies through clinical investigations," said Dr. William CAO, CEO of Gracell. "These invaluable data provides guidance for and enhance our confidence in pipeline selection."

Oral presentations:

A Feasibility and Safety Study of a New CD19-Directed Fast CAR-T Therapy for Refractory and Relapsed B cell Acute Lymphoblastic LeukemiaAbstract #825Session Name: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Therapeutics StrategiesPresenter: Peihua Lu, M.D., Hebei Yanda Lu Daopei HospitalLocation: Orange County Convention Center, Tangerine 1 (WF1), Level 2Time: 5:00 pm, Monday, December 9, 2019https://ash.confex.com/ash/2019/webprogram/Paper121751.html

Anti-CD19/CD22 Dual CAR-T Therapy for Refractory and Relapsed B-Cell Acute Lymphoblastic LeukemiaAbstract #284Session Name: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Novel TherapiesPresenter: Peihua Lu, M.D., Hebei Yanda Lu Daopei HospitalLocation: Orange County Convention Center, W224, Level 2Time: 4:15pm, Saturday, December 7, 2019https://ash.confex.com/ash/2019/webprogram/Paper126429.html

Poster presentations:

CD19-Directed Fast CART Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia: From Bench to BedsideAbstract #1340Session Name: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster IPresenter: Cheng Zhang, M.D., Xinqiao Hospital of AMULocation: Orange County Convention Center, Hall B, Level 25:30-7:30 pm, Saturday, December 7, 2019https://ash.confex.com/ash/2019/webprogram/Paper128006.html

A Bcma and CD19 Bispecific CAR-T for Relapsed and Refractory Multiple MyelomaAbstract # 3147Session Name: 653. Myeloma: Therapy, excluding Transplantation: Poster IIPresenter: Hua Zhang, PhD., Gracell Biotechnology Ltd., Shanghai, China, Shanghai, ChinaLocation: Orange County Convention Center, Hall B, Level 26:00 PM-8:00 pm, Sunday, December 8, 2019https://ash.confex.com/ash/2019/webprogram/Paper131056.html

Role of Donor-Derived CD19.CAR-T Cells in Treating Patients That Relapsed after Allogeneic Hematopoietic Stem Cell TransplantationAbstract #4561Session Name: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence: Poster IIIPresenter: Cheng Zhang, M.D., Xinqiao Hospital of AMULocation: Orange County Convention Center, Hall B, Level 26:00-8:00 pm, Monday, December 9, 2019https://ash.confex.com/ash/2019/webprogram/Paper128262.html

About FasT CAR-19

FasT CAR-19, or GC007F, is an investigational CD19-targeted CAR-T cell therapy for adolescent and adult patients with refractory or relapsed B-ALL, as well as aggressive non-Hodgkin lymphoma. Thanks to Gracell's patented FasTCAR technology, the bioprocessing time for GC007F has been significantly reduced from two weeks to 24 hours with substantially lower cost. The improved CAR-T cell fitness resulted in superior proliferation capabilities, potency, and extensive bone marrow migration making GC007F a potential best-in-class therapy for refractory or relapsed B-ALL.

About Dual CAR-19-22

Dual CAR-19-22, or GC022, is an investigational CAR-T cell therapy redirected to target CD19 and CD22, in treating patients with CD19+, or/and CD22+ relapsed/refractory B-ALL. A low toxicity with dose-dependent high CR rate including patients who previously treated with CD19 CAR-T cells were observed.

About Dual CAR-BCMA-19

Dual CAR-BCMA-19, or GC012, is an investigational CAR-T cell therapy redirected to target BCMA and CD19, in treating patients with BCMA+, or/and CD19+ relapsed/refractory multiple myeloma. Previous research shows CD19 could express on the myeloma progenitor cells, while BCMA is a well validated target for MM.

About Donor CAR-19

Donor CAR-19, or GC007G, is an investigational CD19 targeted CAR-T cell therapy manufactured in use of donor's lymphocytes. The objective of this study is to further investigate and better understand the safety and efficacy of donor derived CAR-T cells in treatment of relapsed and refractory B-ALL patients.

About B-ALL

B-ALL is a sub-type of acute lymphoblastic leukemia, although rare, is one of the most common forms of cancer in children between the ages of two and five and adults over the age of 50[1]. In 2015, ALL affected around 876,000 people globally and resulted in 110,000 deaths worldwide[2]. It is also the most common cause of cancer and death from cancer among children. ALL is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy carried out over several years.

About MM

Myeloma begins when a plasma cell becomes abnormal. The abnormal cell divides to make copies of itself. These abnormal plasma cells are called myeloma cells. In time, myeloma cells collect in the bone marrow. They may damage the solid part of the bone. When myeloma cells collect in several of your bones, the disease is called "multiple myeloma." This disease may also harm other tissues and organs, such as the kidneys. Myeloma cells make antibodies called M proteins and other proteins. These proteins can collect in the blood, urine, and organs[3].

About Gracell

Gracell Biotechnologies Co., Ltd. ("Gracell") is a clinical-stage biopharma company, committed to developing highly reliable and affordable cell gene therapies for cancer. Gracell is dedicated to resolving the remaining challenges in CAR-T, such as high production costs, lengthy manufacturing process, lack of off-the-shelf products, and inefficacy against solid tumors. Led by a group of world-class scientists, Gracell is advancing FasTCAR, TruUCAR (off-the-shelf CAR), Dual CAR and Enhanced CAR-T cell therapies for leukemia, lymphoma, myeloma, and solid tumors.

CONTACT:

Linc HE Associate Director of Business Developmentsunwei.he@gracellbio.com

Dr. William Cao Founder, Chairman and CEOwilliam.cao@gracellbio.com

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Gracell Announces Five Presentations at the Annual Meeting of American Society of Hematology (ASH) - BioSpace

Broncos Briefs: CB Bryce Callahan headed to surgery to replace bent screw in foot – Longmont Times-Call

Cornerback Bryce Callahans first year with the Broncos will end without appearing in a game.

Coach Vic Fangio said after practice Friday that Callahan will be placed on injured reserve and will need foot surgery to replace a bent screw that was initially installed last December.

Signed to a three-year, $21 million contract in March to serve as the No. 2 corner behind Chris Harris, Callahan was shut down after getting stepped on in practice July 27. He was a limited practice participant five times in Weeks 1-2 before being shut down for 4-6 weeks after receiving stem-cell treatment.

Callahans last attempt to practice was Tuesday.

Receiver Tim Patrick (hand) will be activated from injured reserve to take Callahans roster spot for Sundays game at Minnesota.

It isnt clear if Callahan getting stepped on bent the screw or just made the injury worse and too much to overcome.

Part of this operation is to put a screw in there to promote healing, Fangio said. The bent screw caused him a lot of discomfort and pain.

Fangio said Callahan will have surgery soon.

Right tackle JaWuan James (knee) and tight end Jeff Heuerman (knee) are listed as doubtful. Receiver DaeSean Hamilton, who injured his knee in Thursdays practice, did limited work Friday and said he will be available to play.

The Vikings ruled out defensive tackle Linval Joseph (knee), right guard Josh Kline (concussion), receiver Adam Thielen (hamstring) and safety Anthony Harris (groin).

Punt return shake-up? The Broncos claimed defensive back/returner Cyrus Jones off waivers from Baltimore on Wednesday.

Special teams coordinator Tom McMahon said Jones run skill on tape, was intriguing.

He gets downhill and makes good decisions, McMahon said. He came in here and hit the ground running.

Will Jones rotate punt returns with Diontae Spencer?

Well have to see, McMahon said. Thats for (the Vikings) to find out.

McGoverns near homecoming. Broncos center Connor McGovern grew up in Fargo, N.D., about three-plus hours from Minneapolis, so this weekends trip to play the Vikings is as close as hell come to a homecoming game.

My parents are getting a whole bunch of tickets, he said. Its like going home. It will be fun.

Growing up, McGovern said he was initially a Green Bay fan because of defensive end Reggie White.

When he was done, I thought I might as well be a Vikings fan since everybody I knew was a Vikings fan and those are the games I watched, said McGovern, who added that his favorite player became running back Adrian Peterson.

Preparing for Allen. The Vikings have one game of video to game plan for Broncos quarterback Brandon Allen.

Its a little harder because of that reason, Vikings coach Mike Zimmer said. You first prepare for the offense and then you prepare for the players so well try and do the best job we can.

I thought (Allen) did a nice job (against Cleveland). He got out of the pocket, he made a lot of good throws and it looked like he settled down after maybe the first series. I think they did a nice job of getting to the plays that he likes and then he made some good throws.

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Broncos Briefs: CB Bryce Callahan headed to surgery to replace bent screw in foot - Longmont Times-Call

Leading Alternative Healing Director of Total Health Institute Reviews and Receives 3rd Fellowship in Stem Cell Therapy – Financialbuzz.com

Chicago, IL, Nov. 14, 2019 (GLOBE NEWSWIRE) Dr. Keith Nemec the clinic director ofTotal Health Institute in Chicago has received yet another fellowship in his advanced research. Most recently Dr. Nemec received his fellowship in Stem Cell Therapy to add to his other fellowships in Regenerative Medicine and Integrative Cancer Therapies.

Dr. Nemec has overseen patient care for the last thirty-five years at Total Health Institute which is an alternative and integrative medical facility. Total Health Institute has seen over 10,000 patients who have traveled from around the world to seek Dr. Nemecs guidance in their healing journey.

Total Health Institute uses unique approach developed by Dr. Nemec called theSystems Sequence Approach to balance cellular communication between the cells, tissues, organs, glands and systems of the body. Dr. Nemec explains It is like knowing the combination to open the lock to complete healing. To open this lock, you must not only know the right systems to balance but also in the right sequence.

Dr. Keith Nemec is very excited about the research in stem cells and stem cell therapy that is why he focused his concentration in this area. According to Dr. Nemec All health and healing starts at the stem cell level. Whether a person has cancer, autoimmune disease or chronic diseases of aging they are all involving stem cells. In cancer, an inflammatory environment has mutated a normal stem cell into a cancer stem cell which is not killed with either chemotherapy nor radiation. This is why many times with conventional cancer treatment alone one tends to see improvements for a season but then return the cancer stem cell retaliates with a vengeance. Dr. Nemec also states Since all cells come from a base stem cell then the answer to all chronic disease can be found in activating the stem cells to produce an anti-inflammatory niche and continual healthy cell renewal.

Dr. Nemec is a member of the American Academy of Anti-Aging Medicine which is the largest and most prestigious group of Regenerative and Anti-Aging Medicine doctors in the world. He received his masters degree in Nutritional Medicine from Morsani College of Medicine. He has also published 5 books including: The Perfect Diet, The Environment of Health and Disease, Seven Basic Steps to Total Health and Total Health = Wholeness. Dr. Nemec has also published numerous health articles including: The Single Unifying Cause of All Disease and The answer to cancer is found in the stem cell and for 18 years he hosted the radio show Your Total Health in Chicago AM1160.

Total Health Institute boasts all 5 starreviews on RateMDs, an A+ rating onBBBand is top rated on Manta.

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Leading Alternative Healing Director of Total Health Institute Reviews and Receives 3rd Fellowship in Stem Cell Therapy - Financialbuzz.com

Celgene Receives CHMP Positive Opinion for REVLIMID (lenalidomide) in Combination With Rituximab for the Treatment of Adult Patients With Previously…

SUMMIT, N.J.--(BUSINESS WIRE)--Celgene Corporation (NASDAQ:CELG) today announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending the approval of REVLIMID (lenalidomide) in combination with rituximab (anti-CD20 antibody) (R) for the treatment of adult patients with previously treated follicular lymphoma (FL) (Grade 1-3a). If approved by the European Commission (EC), R2 will be the first combination treatment regimen for patients with FL that does not include chemotherapy.

Since its initial approval in 2007, REVLIMID has continued to demonstrate its benefits across a range of serious blood disorders in Europe and a CHMP positive opinion for this combination with rituximab is very good news for patients with follicular lymphoma. We look forward to the European Commission decision, said Tuomo Ptsi, President of Hematology/Oncology for Celgene Worldwide Markets.

In FL, a subtype of indolent NHL, the immune system is not functioning optimally.1,2 When this dysfunction occurs, the immune system either fails to detect or attack cancerous cells.1,2 Rituximab is a monoclonal antibody that targets the CD 20 antigen on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab causes B-cell lysis. Lenalidomide is an immunomodulator that increases the number and activation of T and natural killer (NK) cells, resulting in the lysis of tumor cells. The R2 combination regimen acts by complementary mechanisms to help the patients immune system to find and destroy the cancer cells.3

Given the incurable nature of FL2, a high unmet medical need exists for the development of novel treatment options with new mechanisms of action and a tolerable safety profile to help improve progression-free survival (PFS) especially in the setting of previously treated FL.

The estimated incidence of NHL in Europe was 100,055 cases in 2018; FL accounts for approximately 25% of all NHL cases and is the most common form of indolent NHL.3,4,5

Chemotherapy is a standard of care for indolent forms of NHL, but most patients will relapse or become refractory to their current treatment, said Prof. John Gribben, President of EHA and Centre for Haemato-Oncology, Barts Cancer Institute, in England The combination of REVLIMID and rituximab could represent a new, chemotherapy-free treatment option for patients with previously treated follicular lymphoma.

The CHMP positive opinion is based primarily on results from the randomized, multi-center, double-blind, Phase 3 AUGMENT study, which evaluated the efficacy and safety of the R combination versus rituximab plus placebo in patients with previously treated FL (n=295).6,7 Additionally, findings from the MAGNIFY study were included as support for the safety and the efficacy of lenalidomide plus rituximab in patients with relapsed or refractory FL, including rituximab refractory FL patients.8

The CHMP reviews applications for all member states of the European Union (EU), as well as Norway, Liechtenstein, and Iceland. The European Commission, which generally follows the recommendation of the CHMP, is expected to make its final decision in approximately two months. If approval is granted, detailed conditions for the use of this product will be described in the REVLIMID Summary of Product Characteristics (SmPC), which will be published in the revised European Public Assessment Report (EPAR).

About Follicular Lymphoma

Lymphoma is a blood cancer that develops in lymphocytes, a type of white blood cell in the immune system that helps protect the body from infection.9 There are two classes of lymphoma Hodgkins lymphoma and non-Hodgkins lymphoma (NHL) each with specific subtypes that determine how the cancer behaves, spreads and should be treated.3,10,11 Other differentiating factors of lymphomas are what type of lymphocyte is affected (T cell or B cell) and how mature the cells are when they become cancerous.11

Follicular lymphoma is the most common indolent (slow-growing) form of NHL, accounting for approximately 25% of all Non-Hodgkin lymphoma (NHL) patients.5,12 Most patients present with advanced disease usually when lymphoma-related symptoms appear (e.g., nodal disease, B symptoms, cytopenia) and receive systemic chemoimmunotherapy.5 While follicular lymphoma patients are generally responsive to initial treatment, the disease course is characterized by recurrent relapses over time with shorter remission periods.13

About AUGMENT

AUGMENT is a Phase 3, randomized, double-blind clinical trial evaluating the efficacy and safety of REVLIMID (lenalidomide) in combination with rituximab (R) versus rituximab plus placebo in patients with previously treated follicular lymphoma (FL). AUGMENT included patients diagnosed with Grade 1, 2 or 3a FL, who were previously treated with at least 1 prior systemic therapy and two previous doses of rituximab. Patients were documented relapsed, refractory or progressive disease following systemic therapy, but were not rituximab-refractory.6,7

The primary endpoint was progression-free survival, defined as the time from date of randomization to the first observation of disease progression or death due to any cause. Secondary and exploratory endpoints included overall response rate, durable complete response rate, complete response rate, duration of response, duration of complete response, overall survival, event-free survival and time to next anti-lymphoma therapy.6,7

About REVLIMID

REVLIMID is approved in Europe and the United States as monotherapy, indicated for the maintenance treatment of adult patients with newly diagnosed multiple myeloma (MM) who have undergone autologous stem cell transplantation. REVLIMID as combination therapy is approved in Europe, in the United States, in Japan and in around 25 other countries for the treatment of adult patients with previously untreated MM who are not eligible for transplant. REVLIMID is also approved in combination with dexamethasone for the treatment of patients with MM who have received at least one prior therapy in nearly 70 countries, encompassing Europe, the Americas, the Middle-East and Asia, and in combination with dexamethasone for the treatment of patients whose disease has progressed after one therapy in Australia and New Zealand.

REVLIMID is also approved in the United States, Canada, Switzerland, Australia, New Zealand and several Latin American countries, as well as Malaysia and Israel, for transfusion-dependent anaemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities and in Europe for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate.

In addition, REVLIMID is approved in Europe for the treatment of patients with mantle cell lymphoma (MCL) and in the United States for the treatment of patients with MCL whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib. In Switzerland, REVLIMID is indicated for the treatment of patients with relapsed or refractory MCL after prior therapy that included bortezomib and chemotherapy/rituximab.

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program, the REVLIMID REMS program.

Information about the REVLIMID REMS program is available at http://www.celgeneriskmanagement.com or by calling the manufacturers toll-free number 1-888-423-5436.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Venous and Arterial Thromboembolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patients underlying risks.

CONTRAINDICATIONS

Pregnancy: REVLIMID can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus

Severe Hypersensitivity Reactions: REVLIMID is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See Boxed WARNINGS

REVLIMID REMS Program: See Boxed WARNINGS: Prescribers and pharmacies must be certified with the REVLIMID REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements

Hematologic Toxicity: REVLIMID can cause significant neutropenia and thrombocytopenia. Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. MM: Patients taking REVLIMID/dex or REVLIMID as maintenance therapy should have their complete blood counts (CBC) assessed every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter. MDS: Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or dose reduction. Please see the Black Box WARNINGS for further information. MCL: Patients taking REVLIMID for MCL should have their CBCs monitored weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly thereafter. Patients may require dose interruption and/or dose reduction

Venous and Arterial Thromboembolism: See Boxed WARNINGS: Venous thromboembolic events (DVT and PE) and arterial thromboses (MI and CVA) are increased in patients treated with REVLIMID. Patients with known risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended and the regimen should be based on patients underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision

Increased Mortality in Patients with CLL: In a clinical trial in the first-line treatment of patients with CLL, single agent REVLIMID therapy increased the risk of death as compared to single agent chlorambucil. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials

Second Primary Malignancies (SPM): In clinical trials in patients with MM receiving REVLIMID, an increase of hematologic plus solid tumor SPM, notably AML and MDS, have been observed. Monitor patients for the development of SPM. Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment

Increased Mortality with Pembrolizumab: In clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered

Severe Cutaneous Reactions: Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. Consider REVLIMID interruption or discontinuation for Grade 2-3 skin rash. Permanently discontinue REVLIMID for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN, or DRESS.

Tumor Lysis Syndrome (TLS): Fatal instances of TLS have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with REVLIMID until TFR resolves to Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physicians discretion

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment (>4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection

Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before start of REVLIMID treatment and during therapy

Early Mortality in Patients with MCL: In another MCL study, there was an increase in early deaths (within 20 weeks), 12.9% in the REVLIMID arm versus 7.1% in the control arm. Risk factors for early deaths include high tumor burden, MIPI score at diagnosis, and high WBC at baseline (10 x 109/L)

Hypersensitivity: Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to REVLIMID has been reported. Permanently discontinue REVLIMID for angioedema and anaphylaxis.

ADVERSE REACTIONS

Multiple Myeloma

Myelodysplastic Syndromes

Mantle Cell Lymphoma

DRUG INTERACTIONS

Periodic monitoring of digoxin plasma levels is recommended due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dex and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin

USE IN SPECIFIC POPULATIONS

Please see full Prescribing Information, including Boxed WARNINGS.

Please see full SmPC for further information.

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit http://www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, Facebook and YouTube.

Forward-Looking Statements

This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made. Celgene undertakes no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond each company's control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in the Annual Report on Form 10-K and other reports of each company filed with the Securities and Exchange Commission, including factors related to the proposed transaction between Bristol-Myers Squibb and Celgene, such as, but not limited to, the risks that: managements time and attention is diverted on transaction related issues; disruption from the transaction make it more difficult to maintain business, contractual and operational relationships; legal proceedings are instituted against Bristol-Myers Squibb, Celgene or the combined company could delay or prevent the proposed transaction; and Bristol-Myers Squibb, Celgene or the combined company is unable to retain key personnel.

1 Scott DW, Gascoyne RD. The tumour microenvironment in B cell lymphomas. Nat Rev Cancer. 2014;14(8):517-534.2 Kridel R, Sehn LH, Gascoyne RD. Pathogenesis of follicular lymphoma. J Clin Invest. 2012;122(10):3424-3431.3 Chiu H, Trisal P, Bjorklund C, et al. Combination lenalidomide-rituximab immunotherapy activates anti-tumour immunity and induces tumour cell death by complementary mechanisms of action in follicular lymphoma. Br J Haematol. 2019;185(2):240-253.4 European Cancer Information System. Estimates of cancer incidence and mortality in 2018, for all countries. Available at: https://ecis.jrc.ec.europa.eu/explorer.php. Accessed August 2019.5 European Society for Medical Oncology. Follicular Lymphoma: A Guide for Patients. 2014. Available at: https://www.esmo.org/content/download/52236/963497/file/EN-Follicular-Lymphoma-Guide-for-Patients.pdf . Accessed September 2019.6 Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2019;10;37(14):1188-1199.7 ClinicalTrials.gov Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin's Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma) (AUGMENT). Available at: https://clinicaltrials.gov/ct2/show/NCT01938001 Accessed September 2019.8 ClinicalTrials.gov Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma (MAGNIFY). Available at: https://clinicaltrials.gov/ct2/show/NCT01996865 Accessed August 2019.9 American Cancer Society. Lymphoma. Available at: https://www.cancer.org/cancer/lymphoma.html. Accessed August 2019.10 American Cancer Society. What is Hodgkin Lymphoma? Available at: https://www.cancer.org/cancer/hodgkin-lymphoma/about/what-is-hodgkin-disease.html. Accessed August 2019.11 American Cancer Society. What is Non-Hodgkin Lymphoma? Available at: https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/what-is-non-hodgkin-lymphoma.html. Accessed August 2019.12 Lymphoma Action. Follicular lymphoma. Available at: https://lymphoma-action.org.uk/types-lymphoma-non-hodgkin-lymphoma/follicular-lymphoma. Accessed November 2019.13 Montoto S, Lopez-Guillermo A, Ferrer A, et al. Survival after progression in patients with follicular lymphoma: analysis of prognostic factors. Ann Oncol. 2002;13(4):523-30.

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Celgene Receives CHMP Positive Opinion for REVLIMID (lenalidomide) in Combination With Rituximab for the Treatment of Adult Patients With Previously...

New Cell Therapy Improves Memory and Stops Seizures Following TBI – University Herald

Irvine, Calif. - November 14, 2019 - Researchers from the University of California, Irvine developed a breakthrough cell therapy to improve memory and prevent seizures in mice following traumatic brain injury. The study, titled "Transplanted interneurons improve memory precision after traumatic brain injury," was published today inNature Communications.

Traumatic brain injuries affect 2 million Americans each year and cause cell death and inflammation in the brain. People who experience a head injury often suffer from lifelong memory loss and can develop epilepsy.

In the study, the UCI team transplanted embryonic progenitor cells capable of generating inhibitory interneurons, a specific type of nerve cell that controls the activity of brain circuits, into the brains of mice with traumatic brain injury. They targeted the hippocampus, a brain region responsible for learning and memory.

The researchers discovered that the transplanted neurons migrated into the injury where they formed new connections with the injured brain cells and thrived long term. Within a month after treatment, the mice showed signs of memory improvement, such as being able to tell the difference between a box where they had an unpleasant experience from one where they did not. They were able to do this just as well as mice that never had a brain injury. The cell transplants also prevented the mice from developing epilepsy, which affected more than half of the mice who were not treated with new interneurons.

"Inhibitory neurons are critically involved in many aspects of memory, and they are extremely vulnerable to dying after a brain injury," said Robert Hunt, PhD, assistant professor of anatomy and neurobiology at UCI School of Medicine who led the study. "While we cannot stop interneurons from dying, it was exciting to find that we can replace them and rebuild their circuits."

This is not the first time Hunt and his team has used interneuron transplantation therapy to restore memory in mice. In 2018, the UCI team used a similar approach, delivered the same way but to newborn mice, to improve memory of mice with a genetic disorder.

Still, this was an exciting advance for the researchers. "The idea to regrow neurons that die off after a brain injury is something that neuroscientists have been trying to do for a long time," Hunt said. "But often, the transplanted cells don't survive, or they aren't able to migrate or develop into functional neurons."

To further test their observations, Hunt and his team silenced the transplanted neurons with a drug, which caused the memory problems to return.

"It was exciting to see the animals' memory problems come back after we silenced the transplanted cells, because it showed that the new neurons really were the reason for the memory improvement," said Bingyao Zhu, a junior specialist and first author of the study.

Currently, there are no treatments for people who experience a head injury. If the results in mice can be replicated in humans, it could have a tremendous impact for patients. The next step is to create interneurons from human stem cells.

"So far, nobody has been able to convincingly create the same types of interneurons from human pluripotent stem cells," Hunt said. "But I think we're close to being able to do this."

Jisu Eom, an undergraduate researcher, also contributed to this study. Funding was provided by the National Institutes of Health.

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New Cell Therapy Improves Memory and Stops Seizures Following TBI - University Herald

The Heart of the Matter: Leveraging Advances in Cardiac Biology to Innovate Gene-Based Therapies for Heart Failure – Physician’s Weekly

Heart failure (HF) is the most frequent cardiovascular diagnosis and exacts significant health and financial costs around the globe. It is estimated that at least 26 million people worldwide are living with HF, including nearly 6 million in the United States.1, 2 One in nine U.S. deaths in 2009 included heart failure as a contributing cause and about 50 percent of people in the U.S. with HF die within five years of diagnosis.2 The annual cost of HF-related healthcare services, medication and missed days of work is estimated at $40 billion in the United States and $108 billion globally.3, 4 Quality of life in HF patients is frequently worse than many other chronic diseases and comorbidities are common.5-7 The challenges of HF are expected to grow, as it is estimated that more than 8 million people in the United States alone will have HF by 2030.2 Current therapies improve quality of life in the short-term and have improved long-term survival but a significant number of patients have Class 3 HF despite optimal medical and device therapy. These patients have limited treatment options beyond heart transplant and left ventricular assist devices (LVAD). New therapeutic approaches that address the underlying causes of HF are needed to improve patient outcomes.

Heart failure is a complex disease process and multiple pathways contribute to its development and progression. Myocardial ischemia is frequently an issue in both ischemic and non-ischemic cardiomyopathy as well as HF with preserved and/or reduced ejection fraction. Myocardial ischemia results in insufficient oxygen and nutrients and leads to hypoxia, cardiomyocyte and fibrosis, which all contribute to the progression of heart failure. More effective angiogenesis may prevent this progression. Cell homing also plays a critical role, as injured cardiac tissue secretes factors that lead to the recruitment, proliferation, migration and differentiation of progenitor cells that can help repair tissue damage. Stromal cell-derived factor (SDF)-1 has been shown to play an important role in cardiac repair by mediating cell homing.10 Mitochondrial energy generation is also impaired in HF, leading to decreased contractility and adverse changes to cardiac architecture.11 Scar tissue formed in response to cardiomyocyte injury or death can compromise the hearts mechanical strength or electrical signaling results in myocardial infarction. Inflammatory responses to cardiac tissue damage can promote inappropriate and chronic inflammation and the expression of pro-inflammatory molecules that lead to pathologic changes to cardiac architecture.12, 13

These pathways offer a variety of potential new targets for therapeutic intervention to prevent the development and progression of HF. This opens the door to the development of novel therapies that address the underlying molecular and cellular causes of disease rather than treating HF symptoms alone.

After decades of development, gene-based therapies are now validated therapeutic modalities for the treatment of inherited retinal disorders and cancer and are undergoing clinical evaluation in a variety of inherited, acute and chronic diseases. Nearly two dozen single gene-based therapies for HF have been evaluated in clinical trials.14 Genes evaluated as monogenic gene therapy for HF in clinical trials include vascular endothelial growth factor (VEGF) and fibroblast growth factor type 4 (FGF4) to promote angiogenesis; adenylyl cyclase type 6 (AC6) and sarco/endoplasmic reticulum Ca2+-ATPase type 2 (SERCA2) to improve cardiac calcium homeostasis, which plays a critical role in the contraction and relaxation of heart muscle; and stromal cell-derived factor-1 (SDF-1) to improve cell homing and promote cardiac tissue repair. Late-stage trials of single gene therapies have yielded conflicting results, raising the question as to whether positively impacting a single pathway can be sufficient to overcome detrimental activity of other pathways that contribute to the development and progression of HF. Other potential limitations to HF therapies evaluated in clinical trials to date include the method of delivery, dose and the potency of vectors and gene products.

Given the multiple molecular and cellular pathways active in HF, a multi-gene approach to HF gene therapy may be needed. Simultaneously delivering multiple genes that target diverse HF-related pathways has the potential to improve cardiac biology and function. A triple gene therapy approach (INXN-4001, Triple-Gene LLC, a majority-owned subsidiary of Intrexon Corporation) is currently in clinical development, with each of the genes targeting a specific HF-related pathway. The investigational drug candidate INXN4001 vector expresses: the S100A1 gene product, which regulates calcium-controlled networks and modulates contractility, excitability, maintenance of cellular metabolism and survival; SDF-1a which recruits stem cells, inhibits apoptosis and supports new blood vessel formation; and VEGF-165 which initiates new vessel formation, endothelial cell migration/activation, stem cell recruitment and tissue regeneration. The hypothesis is that the simultaneous delivery of multiple genes in a single vector would more effectively improve multiple aspects of cardiac function compared with single gene therapy. It is delivered by retrograde coronary sinus infusion of a triple effector plasmid designed with a self-cleaving linker to constitutively express human S100A1, SDF-1a and VEGF 165. This route is designed to allow for delivery of a dose to the ventricle which may help achieve improved therapeutic effect.

Several preclinical studies have set the foundation on which to advance a triple gene therapy for HF into the clinic.15-17 Using in vitro studies, transfecting cells derived from patients with dilated cardiomyopathy with a triple gene combination demonstrated improvement in contraction rate and duration, to the levels demonstrated by the control cells and did not result in increased cell death compared to controls.15 Studies in an Adriamycin-induced cardiomyopathy rodent model demonstrated triple gene therapy increased fractional shortening and myocardial wall thickness compared to controls.16 In addition, retrograde coronary sinus infusion of INXN-4001 in a porcine model of ischemic HF resulted in a cardiac-specific biodistribution profile.17

A Phase 1 clinical study has been initiated to evaluate the safety of a single dose of triple gene therapy in stable patients implanted with a LVAD for mechanical support of end-stage HF. An independent Data and Safety Monitoring Board agreed to proceeding to the second cohort following review of the data from the first cohort in the multi-site study.18 The study is ongoing and final results will help to inform our understanding of the potential that multi-gene therapy may play in the treatment of HF.

The recent FDA approvals of gene therapies for an inherited retinal disease and cancer are evidence that gene therapy is a valid therapeutic strategy. Realizing the potential of gene therapy in HF will require appropriately designed clinical trials, but several interesting approaches currently in development may prove to be effective. The results of the initial investigational drug INXN-4001 Phase 1 trial should provide insight into the safety of combining S100A1, SDF-1a and VEGF-165. Evaluation of additional multi-gene combinations will also be important for understanding which targeted pathways yield the greatest effects with respect to relevant clinical endpoints. Continued refinement and optimization of vector design and delivery methods will also be important for advancing further HF gene therapies from bench to bedside.

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The Heart of the Matter: Leveraging Advances in Cardiac Biology to Innovate Gene-Based Therapies for Heart Failure - Physician's Weekly