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Calidi Biotherapeutics Announces Appointment of W.K. Alfred Yung, M.D., to its Medical Advisory Board – Business Wire

By adminJune 29, 2022Stem Cell Medical Center

LA JOLLA, Calif.--(BUSINESS WIRE)--Calidi Biotherapeutics, Inc., a clinical-stage biotechnology company that is pioneering the development of stem cell-based delivery of oncolytic viruses, today announced the appointment of W.K. Alfred Yung, M.D., Professor, Neuro-Oncology at the MD Anderson Cancer Center, to its Medical Advisory Board.

We are inspired by clinician-scientists like Dr. Yung who have dedicated their careers to advancing care for patients with deadly cancers, such as glioblastoma, for which there are few effective treatments, said Allan J. Camaisa, Chief Executive Officer and Chairman of Calidi. As clinical trials studying the safety and efficacy of Calidis oncolytic virus-based therapies progress, the expertise of seasoned clinicians like Dr. Yung will help us further our understanding of the benefits of these drugs to patients.

Dr. Yung is a fixture in the treatment of brain cancers with extensive experience studying glioblastoma, the deadliest form of brain cancer. He built the neuro-oncology department at MD Anderson Cancer Center, served as co-chair of the National Cancer Institute Brain Malignancy Steering Committee, and advised President Bidens Cancer Moonshot Initiative. Dr. Yung has published more than 350 peer-reviewed articles and served as the editor-in-chief of Neuro-Oncology.

Despite many promising new advancements in precision medicine for many cancers, glioblastoma remains one of the deadliest cancers with limited treatment successes and poor patient quality of life, said W. K. Alfred Yung, M.D. I see great promise in the potential of Calidi Biotherapeutics therapeutic vaccine which shields cancer-fighting oncolytic viruses in stem cells, helping protect the virus from a patients immune system until it reaches the cancer cell. If this approach proves successful in human trials, it could be a game changer not just for the treatment of brain cancers, but for other solid tumor cancers too.

About Calidi Biotherapeutics

Calidi Biotherapeutics is a clinical-stage immuno-oncology company with proprietary technology that is revolutionizing the effective delivery of oncolytic viruses for targeted therapy against difficult-to-treat cancers. Calidi Biotherapeutics is advancing through the FDA approval process a potent allogeneic stem cell and oncolytic virus combination for use in multiple oncology indications. Calidis off-the-shelf, universal cell-based delivery platform is designed to protect, amplify, and potentiate oncolytic viruses currently in development leading to enhanced efficacy and improved patient safety. Calidi Biotherapeutics is headquartered in La Jolla, California. For more information, please visit http://www.calidibio.com.

Forward-Looking Statement

This press release contains forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. Terms such as anticipates, believe, continue, could, estimate, expect, intends, may, might, plan, possible, potential, predicts, project, should, would as well as similar terms, are forward-looking in nature. The forward-looking statements contained in this discussion are based on the Calidis current expectations and beliefs concerning future developments and their potential effects. There can be no assurance that future developments affecting Calidi will be those that it has anticipated. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond Calidis control) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: the occurrence of any event, change or other circumstances that could give rise to the termination of negotiations and any subsequent definitive agreements with respect to the business combination (the Business Combination) with Edoc Acquisition Corp. (Edoc); the outcome of any legal proceedings that may be instituted against Edoc, Calidi, the combined company or others following the announcement of the Business Combination, the private placement financing proposed to be consummated concurrently with the Business Combination (the PIPE), and any definitive agreements with respect thereto; the inability to complete the Business Combination due to the failure to obtain approval of the shareholders of Edoc, the possibility that due diligence completed following execution of the principal definitive transaction documents for the Business Combination and PIPE will not be satisfactorily concluded, the inability to complete the PIPE or other financing needed to complete the Business Combination, or to satisfy other conditions to closing; changes to the proposed structure of the Business Combination that may be required or appropriate as a result of applicable laws or regulations or as a condition to obtaining regulatory approval of the Business Combination; the ability to meet stock exchange listing standards following the consummation of the Business Combination; the risk that the Business Combination disrupts current plans and operations of Calidi as a result of the announcement and consummation of the Business Combination; the ability to recognize the anticipated benefits of the Business Combination or to realize estimated pro forma results and underlying assumptions, including with respect to estimated shareholder redemptions; costs related to the Business Combination; changes in applicable laws or regulations; the evolution of the markets in which Calidi competes; the inability of Calidi to defend its intellectual property and satisfy regulatory requirements; the ability to implement business plans, forecasts, and other expectations after the completion of the proposed Business Combination, and identify and realize additional opportunities; the risk of downturns and a changing regulatory landscape in the highly competitive pharmaceutical industry; the impact of the COVID-19 pandemic on Calidis business; and other risks and uncertainties set forth in the section entitled Risk Factors and Cautionary Note Regarding Forward-Looking Statements in Edocs preliminary prospectus dated March 16, 2022, in the Registration Statement on Form S-4 filed with the Securities and Exchange Commission (SEC) on March 16, 2022.

Important Information About the Business Combination Transaction and Where to Find It

This press release relates to a proposed business combination between Edoc Acquisition Corp. a Cayman Islands exempted company, EDOC Merger Sub Inc., a Nevada corporation and Calidi Biotherapeutics, Inc., a Nevada corporation. A full description of the terms and conditions Agreement and Plan of Merger constituting the business combination is provided in the registration statement on Form S-4 filed with the U.S. Securities and Exchange Commission (SEC) by Edoc Acquisition Corp., that includes a prospectus with respect to the securities to be issued in connection with the merger, and information with respect to an extraordinary meeting of Edoc Acquisition Corp. shareholders to vote on the merger and related transactions. Edoc Acquisition Corp. and Calidi Biotherapeutics, Inc. urges its investors, shareholders and other interested persons to read the proxy statement and prospectus as well as other documents filed with the SEC because these documents will contain important information about Calidi Biotherapeutics, Inc., Edoc Acquisition Corp., and the business combination transaction. After the registration statement is declared effective, the definitive proxy statement and prospectus to be included in the registration statement will be distributed to shareholders of Edoc Acquisition Corp. and Calidi Biotherapeutics, Inc., as of a record date to be established for voting on the proposed merger and related transactions. Shareholders may obtain a copy of the Form S-4 registration statement, including the proxy statement and prospectus, and other documents filed with the SEC without charge, by directing a request to: Edoc Acquisition Corp. at 7612 Main Street Fishers, Suite 200, Victor, New York 14564. The preliminary and definitive proxy statement and prospectus included in the registration statement can also be obtained, without charge, at the SECs website (www.sec.gov).

Participation in the Solicitation

Edoc Acquisition Corp., Calidi Biotherapeutics, Inc., and their respective directors and executive officers may be deemed to be participants in the solicitation of proxies or consents from Edoc Acquisition Corp. and Calidi Biotherapeutics, Inc. shareholders in connection with the proposed transaction. A list of the names of the directors and executive officers of Edoc Acquisition Corp. and Calidi Biotherapeutics, Inc. and information regarding their interests in the business combination transaction is contained in the proxy statement and prospectus. You may obtain free copies of these documents as described in the preceding paragraph.

No Offer or Solicitation

This press release will not constitute a solicitation of a proxy, consent or authorization with respect to any securities or in respect of the proposed business combination. This press release will also not constitute an offer to sell or the solicitation of an offer to buy any securities of Calidi Biotherapeutics, Inc., nor will there be any sale of securities in any states or jurisdictions in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities will be made except by means of a prospectus meeting the requirements of section 10 of the Securities Act of 1933, as amended, or an exemption therefrom.

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Calidi Biotherapeutics Announces Appointment of W.K. Alfred Yung, M.D., to its Medical Advisory Board - Business Wire

NYU Langone Health Continues to Rapidly Expand Its Outpatient Network – NYU Langone Health

By adminJune 29, 2022Stem Cell Medical Center

NYU Langone Health continues to broaden access to high-quality primary and specialty care with recent expansions on Long Island and in Brooklyn and southeast Florida.

Were continually evolving our network to better meet our patients needs, says Andrew Rubin, senior vice president for clinical affairs and ambulatory care at NYU Langone. Whether were adding new services or opening up new practices, our goal is to make it easier for patients to access integrated, comprehensive, patient-centered care in the communities we serve.

Expanding the breadth and depth of services on Long Island, NYU Langone recently added the following practices and providers.

Three new practices at 100 Hospital Road in Patchogue offer multispecialty and surgical care as part of a broader expansion to bring more healthcare services to Suffolk County. The care team at NYU Langone Long Island Surgical AssociatesPatchogue, 100 Hospital Road specializes in breast, colorectal, general, and urologic surgery consultations. Radiation oncology consultations are also available on-site at Perlmutter Cancer Center Radiation Oncology at NYU LangonePatchogue. At NYU Langone Medical AssociatesPatchogue, 100 Hospital Road, the team offers family medicine care for patients age 16 and older, and gastroenterology, podiatry, and urology services.

Vascular surgeon Jonathon A. Rubin, MD, is now seeing patients at NYU Langone Cardiology AssociatesEast Patchogue.

Neurosurgeons Richard W. Johnson, MD, Ricky Madhok, MD, and David Chen, DO, recently joined NYU Langones neurosurgery department at NYU Langone HospitalLong Island, and see patients at NYU Langone Ambulatory Care East Meadow, NYU Langone Huntington Medical Group, and NYU Langone Neurosurgery AssociatesKew Gardens.

At NYU Langone Ambulatory Care East Meadow, occupational and physical therapy and speechlanguage pathology experts at NYU Langones Rusk Rehabilitation now provide specialized care for people with neurologic conditions.

NYU Langone also continues to extend its reach in Brooklyn with the opening of a new location and expanded services.

NYU Langone opened a second care center in Greenpoint, NYU Langone Brooklyn Medical AssociatesKent Street, located in the historic Eberhard Faber Pencil Factory. This new practice offers bariatric and orthopedic surgery consultations, gastroenterology and endoscopy services, on-site diagnostic imaging at NYU Langone RadiologyGreenpoint, and physical therapy through NYU Langones Rusk Rehabilitation.

New clinical services available at NYU Langone Brooklyn Medical AssociatesDyker Heights include bariatric and general surgery consultations, gastroenterology, endocrinology, and pulmonology.

Swapna Ghanta, MD, a breast surgeon and oncologist at Perlmutter Cancer CenterSunset Park who specializes in advanced breast surgery and reconstruction techniques, has joined the medical team at NYU Langone Brooklyn Medical Associates902 Quentin Road. Dr. Ghanta also sees patients at high risk of developing breast cancer.

In Palm Beach County, Florida, NYU Langone recently introduced orthopedics and womens health services and expanded its medical weight loss program to enhance access to comprehensive care at NYU Langone Medical AssociatesWest Palm Beach.

The team here welcomes Dennis A. Cardone, DO, and John G. Kennedy, MD, two of New Yorks leading sports medicine and orthopedic surgery physicians, who are now seeing patients in West Palm Beach. They treat injuries with the goal of optimizing performance, and a rapid and safe return to play. They specialize in sports regenerative medicine techniques for soft tissue and joint conditions, including platelet-rich plasma (PRP), concentrated bone marrow aspirate (CBMA), and fat stem cell transplant treatments. Dr. Kennedy also performs in-office needle arthroscopy (IONA) in Floridas first fully equipped IONA facility. IONA is a minimally invasive procedure performed on joints and tendons in the office, leading to significant pain reduction, a low complication rate, and excellent patient-reported outcomes.

The team also welcomes gynecologist Raquel B. Dardik, MD, who provides preventive care and management of conditions affecting the female reproductive system from puberty through menopause and beyond.

In addition, social worker Deborah Lifschitz, LCSW, helps support the emotional needs of patients enrolled in the medical weight loss program at NYU Langone Medical AssociatesWest Palm Beach and offers general mental health counseling services. Lifschitz also sees patients at NYU Langone Medical AssociatesDelray Beach.

We invest in the health of our communities by bringing more physicians into newer facilities with the latest technology and equipment, which we believe leads to better patient outcomes, says Rubin. No matter where they are seen, patients can expect the highest level of care across NYU Langone.

Deborah DJ Haffeman Phone: 646-284-5630 deborah.haffeman@nyulangone.org

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NYU Langone Health Continues to Rapidly Expand Its Outpatient Network - NYU Langone Health

Veloxis Pharmaceuticals Announces Dosing of the First Patient by partner Xenikos in the Global Phase 3 Study Evaluating T-Guard in Patients with…

By adminJune 29, 2022Stem Cell Medical Center

T-Guard, under development by Xenikos B.V., is being studied in comparison to ruxolitinib in patients with Grade III or IV SR-aGHVD

CARY, N.C., June 28, 2022 /PRNewswire/ -- Veloxis Pharmaceuticals, an Ashai Kasei company, today announced dosing of the first patient by its partner, Xenikos, in a global pivotal Phase 3 clinical study [NCT04934670] designed to evaluate T-Guard versus ruxolitinib for the treatment of patients with Grade III or IV steroid-refractory acute graft-versus-host disease (SR-aGVHD) following allogeneic hematopoietic stem cell transplant (allo-HSCT). T-Guard is currently being developed by Xenikos B.V., a privately-held biotechnology company that develops innovative immunotherapies for treating patients with severe immune disease and post-transplant rejection.

(PRNewsfoto/Veloxis Pharmaceuticals)

This study comparing T-Guard to ruxolitinib, if successful, can help bring a new treatment option to patients.

In September 2021, Xenikos secured40 million in convertible debt consisting of two equal tranches of 20 million, led by Veloxis Pharmaceuticals with participation from existing investors, Medicxi, RA Capital Management, Oost NL and Sanquinnovate. In connection with the financing, Veloxis has obtained two sequential call options to acquire the company.

"Patients who experience SR-aGVHD have limited treatment options and sadly, their condition is often fatal" said Ulf Meier-Kriesche, chief scientific officer of Veloxis. "This Phase 3 study comparing T-Guard, with its novel mechanism of action, to ruxolitinib, if successful, can help bring a new treatment option to patients who urgently need it."

"Veloxis is looking forward to the potential addition of T-Guard to its pipeline as we develop a broad portfolio of novel drugs to meet the needs of different groups of transplant patients," says Mark Hensley, CEO of Veloxis.

Xenikos reached agreement with the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA) on the design of this global, pivotal, randomized Phase 3 study, which is planned to enroll 246 patients and has been designed to test for superiority of T-Guard compared to ruxolitinib for the treatment of Grade III or IV SR-aGVHD. The study will be conducted at 75 transplant centers across the U.S. and Europe and will be executed in collaboration with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Patients will be randomized 1:1 to receive either T-Guard or ruxolitinib. Participants in the T-Guard arm will receive a one-week course of treatment with T-Guard as a four-hour infusion every other day. Each dose consists of 4mg/m2 body surface area (BSA). Participants in the ruxolitinib arm will receive 10mg of ruxolitinib twice daily for a minimum of 56 days.

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The primary endpoint of the study is complete response (CR) rate at Day 28, which is an important surrogate for long-term survival in patients with SR-aGVHD. Key secondary objectives include overall survival at Days 60, 90, 180 and 365, duration of complete response (CR), time to CR, overall response rate at Days 14, 28 and 56, GVHD-free survival, incidence of infections and safety.

There will be a safety run-in phase at the beginning of the study whereby the Data and Safety Monitoring Board (DSMB) will evaluate the first 24 patients. Xenikos expects to report results from the safety run-in phase during the first half of 2023. The trial will also include an interim analysis for futility after 46 patients become evaluable for the primary endpoint. A second interim analysis will be performed once 150 participants have reached Day 28.

Xenikos expects the data from this study to support the submission of a Biologics License Application (BLA) in the U.S. based on Day 28 data from the first 150 patients. Data from the full 246 patients is expected to support the submission of a Marketing Authorization Application (MAA) in the EU.

Acute Graft-Versus-Host Disease

Following allogeneic stem cell transplantation, most patients have a high risk of developing graft-versus-host disease (GVHD). With GVHD, the donor's immune cells attack the patient's cells. Acute GVHD occurs early after transplantation and can be relatively mild or quite severe, even life-threatening, if not treated. Although GVHD can often be treated successfully with steroids, few options are available if the disease progresses or becomes resistant to steroid treatment, and the long-term survival of patients with steroid-refractory acute GVHD (SR-aGVHD) is less than 20%, highlighting the urgent need for effective new therapies.

T-Guard: Helping Reset the Body's Immune System

T-Guard is designed to reset the body's immune system in life-threatening T cellmediated conditions, potentially including prevention of transplant-related rejection, treatment of acute solid-organ rejection, and severe autoimmune disease. T-Guard consists of a unique combination of toxin-conjugated monoclonal antibodies that target CD3 and CD7 molecules on immune cells. Preclinical and early clinical testing have shown that T-Guard can specifically identify and eliminate mature T cells and NK cells with tolerable treatment-related side effects. T-Guard's action is believed to be short-lived, which may alter a patient's vulnerability to opportunistic infections compared to currently available therapies. T-Guard has been previously studied in a Phase 1/2 study in comparison to institutional historical controls in patients being treated second-line for SR-aGVHD following hematopoietic stem cell transplantation (HSCT). To learn more about that study, please find it here (link). T-Guard has been granted Orphan Drug Designation in both the EU and the U.S.

About the Blood and Marrow Transplant Clinical Trials Network (BMT CTN)

The BMT CTN conducts rigorous multi-institutional clinical trials of high scientific merit, focused on improving survival for patients undergoing hematopoietic cell transplantation and/or receiving other cellular therapies. The BMT CTN has completed accrual to more than 50 Phase II and III trials at more than 100 transplant centers and enrolled over 16,000 study participants.

BMT CTN is funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute, both parts of the National Institutes of Health (NIH) and is a collaborative effort of 20 Core Transplant Centers/Consortia, the Center for International Blood and Marrow Transplant Research (CIBMTR), the National Marrow Donor Program (NMDP)/Be The Match and the Emmes Company, LLC, a clinical research organization. CIBMTR is a research collaboration between the NMDP/Be The Match and the Medical College of Wisconsin.

The BMT CTN 2002 study is being led by Drs. Mehdi Hamadani, Protocol Officer, Scientific Director of CIBMTR, Medical College of Wisconsin; John Levine, Protocol Co-chair, Director of BMT Clinical Research, Mt. Sinai School of Medicine; Grard Soci, Protocol Co-chair, Head of Hematology-Transplantation, Hpital Saint-Louis; and Gabrielle Meyers, Protocol Co-chair, Associate Professor of Medicine, Oregon Health and Science University. More information about the BMT CTN can be found at bmtctn.net.

About Xenikos

Xenikos develops innovative immunotherapies based on conjugated antibodies. This novel therapeutic approach helps reset the immune system in patients who have a severe immune disease or have developed post-transplantation rejection. A randomized Phase 3 registration trial evaluating the company's flagship product, T-Guard for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) is underway in the U.S. and Europe.

About Veloxis Pharmaceuticals

Veloxis Pharmaceuticals, Inc, an Asahi Kasei company, is a fully integrated specialty pharmaceutical company committed to improving the lives of transplant patients. Headquartered in Cary, North Carolina, USA, Veloxis is focused on the global development and commercialization of medications utilized by transplant patients and by patients with serious related diseases. For further information, please visitwww.veloxis.com.

About Asahi Kasei

The Asahi Kasei Group contributes to life and living for people around the world. Since its foundation in 1922 with ammonia and cellulose fiber business, Asahi Kasei has consistently grown through the proactive transformation of its business portfolio to meet the evolving needs of every age. With more than 40,000 employees around the world, the company contributes to sustainable society by providing solutions to the world's challenges through its three business sectors of Material, Homes, and Healthcare. Its healthcare operations include devices and systems for acute critical care, dialysis, therapeutic apheresis, transfusion, and manufacture of biotherapeutics, as well as pharmaceuticals and diagnostic reagents. For further information, please visitwww.asahi-kasei.com.

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Cellectis Announces the Appointment of Axel-Sven Malkomes & Dr. Donald A Bergstrom, M.D., Ph.D., to its Board of Directors – Yahoo Finance

By adminJune 29, 2022Stem Cell Medical Center

Cellectis Inc.

NEW YORK, June 28, 2022 (GLOBE NEWSWIRE) -- Cellectis (the Company) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, today announced that during the annual shareholders meeting, Axel-Sven Malkomes and Donald Bergstrom, M.D., Ph.D., have been appointed as Directors of the Companys Board of Directors, effective immediately.

We are pleased to continue our work with Dr. Bergstrom and to welcome Mr. Malkomes to the Cellectis Board. They are both seasoned leaders within the healthcare industry, who bring decades of experience in both the healthcare and financial services sectors to Cellectis. We are confident they will provide meaningful and valued perspectives as we continue to progress toward becoming one of the few end-to-end cell and gene therapy companies, said Dr. Andr Choulika, Chief Executive Officer.

Donald A Bergstrom, M.D., Ph.D.

As of today, Dr. Bergstrom will serve as Director of Cellectis Board. Previously, Donald A Bergstrom, M.D., Ph.D., was appointed as a Board Observer on the Companys Board of Directors on November 4, 2021.

Dr. Bergstrom currently serves as Executive Vice President, Head of Research and Development at Relay Therapeutics, Inc., a clinical-stage precision medicines company. He brings with him over 15 years of experience in the biopharmaceutical and medical industries.

Prior to his tenure at Relay Therapeutics, Dr. Bergstrom was Chief Medical Officer at Mersana Therapeutics, where he led the advancement of two products based on Mersanas proprietary antibody-drug conjugate platform through non-clinical development and into Phase 1 clinical trials. Prior to Mersana, he was Global Head of Translational and Experimental Medicine at Sanofi Oncology. At Sanofi, Dr. Bergstrom held roles of increasing responsibility at Merck Research Laboratories, culminating in his role as Oncology Franchise Lead, Experimental Medicine. Dr. Bergstrom holds an M.D. from the University of Washington, Seattle, and a Ph.D. from the Fred Hutchinson Cancer Research Center, where he also completed his post-doctoral training. He was a resident in clinical pathology at the University of Washington.

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Axel-Sven Malkomes

Axel-Sven Malkomes served as Chief Financial Officer & Chief Business Officer at Medigene AG, a clinical stage immuno-oncology company focusing on the development of T-cell immunotherapies for the treatment of cancer, until March 31st, 2022. He brings with him over 25 years of experience in the healthcare sector.

Previous to his tenure at Medigene, Mr. Malkomes served as Vice Chairman & Managing Director of the Life Sciences Practice for the British bank Barclays in Europe. Prior to joiningBarclays, he was Global Head of Healthcare & Chemicals Investment Banking at the French corporate and investment bank Socit Gnrale.

On the investor side, Mr. Malkomes has accumulated relevant experience during his several years with the UK listedprivate equity firm 3iplc.as co-head of European Healthcare Investments. Previously, he had leading operational and corporate roles at the German pharmaceutical company Merck KGaA, i.e. as Head of Strategic Planning as well as Head ofMergers & Acquisitions/Business Development, where he significantly participated in the initial set-up and build-out of the company's oncology business.

During his international management career, Mr. Malkomes gained extensive knowledge of the pharmaceutical industry.

About Cellectis Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. Cellectis utilizes an allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with over 22 years of expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to treat diseases with unmet medical needs. As part of its commitment to a cure, Cellectis remains dedicated to its goal of providing lifesaving UCART product candidates for multiple cancers including acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL) and multiple myeloma (MM). .HEAL is a new platform focusing on hemopoietic stem cells to treat blood disorders, immunodeficiencies and lysosomal storage diseases. Cellectis headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS).

For more information, visit http://www.cellectis.com Follow Cellectis on social media: @cellectis, LinkedIn and YouTube.

For further information, please contact:

Media contacts: Pascalyne Wilson, Director, Communications, +33776991433, media@cellectis.com Margaret Gandolfo, Senior Manager, Communications, +1 (646) 628 0300

Investor Relation contact: Arthur Stril, Chief Business Officer, +1 (347) 809 5980, investors@cellectis.com Ashley R. Robinson, LifeSci Advisors, +1 (617) 430 7577

Forward-looking Statements This press release contains forward-looking statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as anticipate, believe, intend, expect, plan, scheduled, could, would and will, or the negative of these and similar expressions. These forward-looking statements, which are based on our managements current expectations and assumptions and on information currently available to management. These forward-looking statements are made in light of information currently available to us and are subject to numerous risks and uncertainties, including with respect to the numerous risks associated with biopharmaceutical product candidate development as well as the duration and severity of the COVID-19 pandemic and governmental and regulatory measures implemented in response to the evolving situation. With respect to our cash runway, our operating plans, including product development plans, may change as a result of various factors, including factors currently unknown to us. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F and the financial report (including the management report) for the year ended December 31, 2021 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

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Cycling knee pain: Where pain occurs, causes, and more – Medical News Today

By adminJune 29, 2022Stem Cell Medical Center

Many cycling injuries occur due to overuse of the joints of the lower body, especially the knees.

In the United States, around 872,000 people commute to work by bicycle, and cycling as a form of exercise has increased in popularity during the COVID-19 pandemic. As a result, cyclists have experienced more injuries, including to the knees.

This article looks at how common knee pain from cycling is, areas where the pain typically occurs, causes of knee pain, and treatments. We also look at ways to look after the knees, prevention of knee pain from cycling, and the outlook for people with knee pain related to cycling.

Knee pain is the most common injury related to overuse reported by cyclists, both by professionals and those who cycle for recreation.

A 2017 study found that the following factors play a significant role in the rate of knee pain, such as:

The study also found that:

Pain caused by cycling can occur in different parts of the knee. These include the anterior, posterior, lateral, and medial areas of the knee.

Anterior pain occurs at the front and center of the knee. Cyclists most commonly experience pain in this part of the knee. Anterior knee pain in cyclists is usually patellofemoral pain (PFP).

Symptoms of PFP include:

Cilta-cel Elicits an ORR of 100% in Multiple Myeloma After Early Relapse on Initial Therapy – OncLive

By adminJune 29, 2022Stem Cell Medical Center

The CAR T-cell therapy ciltacabtagene autoleucel generated a high response rate in patients with multiple myeloma who experienced early clinical relapse or failure to initial therapy.

The CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel; Carvykti) generated a high response rate in patients with multiple myeloma who experienced early clinical relapse or failure to initial therapy, according to data from cohort B of the phase 2 CARTITUDE-2 trial (NCT04133636) presented during the 2022 EHA Congress.1

At a median follow-up of 13.4 months (range, 5.2-21.7), cilta-cel produced an overall response rate (ORR) of 100% (95% CI, 82.4%-100%) in 19 patients; 90% of patients achieved a complete response (CR) or better and 95% had a very good partial response (VGPR) or better. The CAR T-cell therapy resulted in a partial response rate of 5%, and a stringent CR of 63%.

Notably, of the 15 patients with minimal residual disease (MRD)evaluable samples, 93.3% (95% CI, 68.1%-99.8%) achieved negativity with treatment.

"These results are consistent with the responses that we [saw] in the phase 1b/2 CARTITUDE-1 trial [NCT03548207] and in [cohort A of] CARTITUDE-2, Niels W.C.J. van de Donk, MD, study author and hematologist at the VU University Medical Center in Amsterdam, The Netherlands, said in a presentation of the data. The efficacy and safety profile of cilta-cel in high-risk patients with multiple myeloma who experienced early clinical research or treatment failure support the continued exploration of cilta-cel in earlier lines of treatment.

In February 2022, the FDA approved cilta-cel for the treatment of adult patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody, based on results from CARTITUDE-1.2

CARTITUDE-2 aimed to further evaluate cilta-cel in select patient populations with multiple myeloma. Prior data from cohort A of the trial demonstrated that patients who received 2 previous lines of therapy experienced an ORR of 95%, including 79% with a CR or better, and 90% with a VGPR or better.3

Efficacy and safety data from cohort B were presented during the 2022 EHA Congress.

Cohort B enrolled patients with multiple myeloma who experienced early relapse following initial treatment that included a PI and an IMiD. Patients were required to have disease progression per International Myeloma Working Group criteria within 12 months after treatment with autologous stem cell transplantation (ASCT) or from the start of anti-myeloma therapy for patients who did not have an ASCT.4

After screening, patients underwent apheresis followed by bridging therapy, as needed. Five days prior to infusion with cilta-cel, patients received 300 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine for 3 days. On day 1 of the study, patients received a cilta-cel infusion with a target dose of 0.75 x 106 CAR-positive viable T cells/kg. Post-infusion assessments were done from day 1 through 100, and posttreatment assessments were conducted from day 101 through the end of the cohort.

The primary end point of CARTITUDE-2 was MRD 10-5 negativity, assessed by next-generation sequencing or next-generation flow. Secondary end points included ORR, duration of response (DOR), time to response, and safety.

Within cohort B, the median age was 58 years (range, 44-67). Most patients were male (73.7%), White (73.7%), had bone marrow plasma cells of less than 60% (78.9%), did not have extramedullary plasmacytomas (84.2%), and did not have a high-risk cytogenetic profile (84.2%). The median time since initial diagnosis was 1.15 years (range, 0.5-1.9), the median prior lines of therapy received was 1 (range, 1-1), and 78.9% of patients underwent prior ASCT. Notably, 21.1% of patients had a triple-class exposure status.

Moreover, 15.8% of patients were triple-class refractory, 78.9% were refractory to their last line of therapy, 78.9% were refractory to lenalidomide (Revlimid), 31.6% were refractory to bortezomib (Velcade), 15.8% were refractory to daratumumab (Darzalex), and 10.5% were refractory to thalidomide.

Additional data showed that the median DOR was not reached with CAR T-cell therapy. The median time to first response was 1.0 month (range, 0.9-9.7), and the median time to best response was 5.1 months (range, 0.9-11.8). The 12-month progression-free survival rate was 89.5% (95% CI, 64.1%-97.3%) with CAR T-cell therapy.

The peak expansion of CAR T cells occurred on day 13 (range, 9-210), and the median CAR T-cell persistence was 77 days (range, 41-222).

Levels of IL-6 and IFN- increased following infusion of cilta-cel, peaking at days 7 through 14 and returning to baseline levels within 2 to 3 months. Notably, the incidence of cytokine release syndrome (CRS) was associated with a higher peak of IL-6 and IFN-.

CRS was reported in 84% of patients; 1 patient had grade 3/4 CRS. The median time to onset of CRS was 8 days (range, 5-11), and the median duration was 3.5 days (range, 1-7). Additionally, 63% of patients received tocilizumab (Actemra) and 21% were given corticosteroids for CRS. This toxicity was resolved in all patients.

Neurotoxicity was reported in 26% of patients, and it had resolved in 3 of 5 patients. One patient experienced grade 1 immune effector cellassociated neurotoxicity syndrome, with a time to onset of 11 days and a duration of 4 days. Another patient experienced grade 3 movement and neurocognitive treatment-emergent adverse effects (MNTs)/parkinsonism that occurred at day 38. Notably, this patient had at least 2 risk factors for MNTs/parkinsonism, and they showed improvement at the time of data cutoff and achieved a CR.

The incidence of MNT and parkinsonism decreased from 6% in CARTITUDE-1 to less than 0.5% after implementation of patient management strategies across the CARTITUDE program, and that includes to administer these patients effective bridging therapy to reduce tumor burden and to treat CRS or icons [early], if it occurs, van de Donk said.

Regarding other safety data, hematologic adverse effects (AEs) of any grade included neutropenia (95%), anemia (58%), thrombocytopenia (58%), lymphopenia (32%), and leukopenia (26%).

Grade 3 or 4 hematologic AEs included neutropenia (90%), anemia (47%), thrombocytopenia (26%), lymphopenia (32%), and leukopenia (26%). Notably, the rate of grade 3/4 cytopenias that did to not improve to grade 2 or less by day 60 was 16% for thrombocytopenia, 11% for lymphopenia, and 11% for neutropenia.

One death occurred on the study, due to progressive disease on day 158. For the 1 patient treated in an outpatient setting, the safety profile of cilta-cel was found to be manageable.

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Cilta-cel Elicits an ORR of 100% in Multiple Myeloma After Early Relapse on Initial Therapy - OncLive

CHMP issues a positive opinion recommending full approval of Oncopeptides Pepaxti in EU for patients with triple class refractory multiple myeloma -…

By adminJune 29, 2022Stem Cell Medical Center

STOCKHOLM, June 23, 2022 /PRNewswire/ --Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO), a biotech company focused on research and development of therapies for difficult-to-treat hematological diseases, today announces that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP), has unanimously adopted a positive opinion recommending a full marketing authorization approval (MAA) of Pepaxti (melphalan flufenamide, also called melflufen) in EU. The European Commission (EC) will make a legally binding decision based on the EMA recommendation within 60 days. Once granted by EC, the marketing authorization is valid in all EU member states, as well as in the European Economic Area (EEA) countries Iceland, Lichtenstein, and Norway.

The positive opinion is based on data from the phase 2 HORIZON study and is supported by data from the randomized controlled phase 3 OCEAN study which was utilized as confirmatory study. No specific post-marketing commitments were issued. Oncopeptides intends to submit a type II variation in Q4 2022 to enable access to earlier lines of treatment for patients with relapsed refractory multiple myeloma (RRMM).

Pepaxti is indicated, in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. For patients with a prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation.

"Pepaxti helps patients with multiple myeloma, an incurable hematologic cancer. Today's positive CHMP opinion confirms that Pepaxti provides benefit to these patients and is foundational for the future of Oncopeptides and our development pipeline," says Jakob Lindberg, CEO of Oncopeptides. "Based on the scientific evaluation by EMA, our dialogue with the US Food and Drug Administration (FDA) has now been intensified to achieve a clear path forward also for US patients."

Efficacy results for triple-class refractory patients who have received at least 3prior lines of therapies and who had no ASCT or progressed more than 36 months after an ASCT in the HORIZON study

Response (n=52)

HORIZON study(assessed by investigator)

Overall response rate (ORR), 95% CI (%)

28.8% (17.1%, 43.1%)

Duration of response (DOR) 95% CI (months)

7.6 (3.0-12.3)

Time to response (TTR) (months)

2.3 (1.0-10.5)

"The recommendation for full approval of Pepaxti by EMA is really good news for patients with triple class refractory disease, where the unmet medical need remains high and treatment options often are exhausted," says Pieter Sonneveld, professor of Hematology at the Erasmus University Medical Center in Rotterdam, the Netherlands and principal investigator of the OCEAN study.

"EMAs assessment of Pepaxti corroborates our scientific conclusion that the overall survival result in the OCEAN study constitutes a case of true survival heterogeneity which is reflected in the indication statement in accordance with the agencys guidelines," says Klaas Bakker, MD, PhD, Executive Vice President, and Chief Medical Officer. "In addition, EMA confirms that there are no toxicological safety signals in both studies and there is a positive benefit risk profile in the indicated patient population. The non-transplanted, often older patient population, which represents the largest group of RRMM patients, particularly benefits from treatment with Pepaxti."

As previously disclosed, Oncopeptides has an EIB loan facility. Oncopeptides and EIB are currently in negotiations, to update tranche definitions to reflect the current regulatory situation. In addition, the Company is considering additional financing options to capture the opportunities with the upcoming EU-approval. This may include new share issues and other public or private financing options.

Oncopeptides will advance market access activities after an approval by the European Commission, to pave the way for a successful launch of Pepaxti in Germany in Q4, 2022. The Company is actively considering various options to commercialize the drug, making it available for patients across Europe, and maximizing shareholder value.

Conference call for investors, analysts, and media

Investors, financial analysts, and media are invited to participate in a webcast with a Q&A session on June 27, 2022, at 11:00 (CET). The event will be hosted by CEO Jakob Lindberg, CMO Klaas Bakker and CFO Annika Muskantor.

Webcast

The webcast will be streamed via https://tv.streamfabriken.com/2022-pressconference. The link can also be found on the website: http://www.oncopeptides.com.

Dial-in number

SE: +46856642695 UK: +443333009270 US: +16467224902

For further information, please contact:

Rolf Gulliksen, Global Head of Corporate Communications, Oncopeptides AB (publ) E-post: [emailprotected] Mobil: + 46 70262 96 28

The information in the press release is information that Oncopeptides is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person above, on June 23, 2022, at 17:55 (CET).

About Pepaxti

Pepaxti (melphalan flufenamide, also called melflufen) is a lipophilic peptide conjugated alkylating drug that rapidly and selectively is delivering cytotoxic agents into tumor cells. The drug is composed of a di-peptide and an alkylating moiety. The lipophilicity allows a faster cellular uptake whereas the peptide hydrolysis mediated by aminopeptidases, results in accumulation of alkylating moieties in cancer cells. This results in an improved efficacy without an increased toxicity compared to melphalan. Pepaxti inhibits proliferation and induces apoptosis of haematopoietic and solid tumour cells. It shows synergistic cytotoxicity in combination with dexamethasone in melphalan resistant and non-resistant multiple myeloma cell lines.

Pepaxti is indicated in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapy, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapies. For patients with a prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation.

About Multiple Myeloma

Multiple myeloma is a cancer that originates in plasma cells, a type of white blood cells which produce antibodies to help fight infection, and cause cancer cells to accumulate in the bone marrow. Multiple Myeloma is the second most common hematologic malignancy, and accounts for approximately 1-2% of all new cancer cases, with a global incidence rate of 1.7 per 100,000 and an age-standardized incidence rate of 2.1-3.4 per 100,000 in France, Germany, Italy, Spain, and the UK. An estimated 35,842 patients were diagnosed in the EU27 during 2020, with an estimated 23,275 deaths due to the disease (ECIS 2020).

Patients with multiple myeloma may have symptom-free periods, but the disease always relapses, and patients may become refractory to all available treatment options due to mutations and/or clonal evolution of the tumor cells.A growing subset of patients are triple-class refractory, and develop disease refractory to immunomodulatory drugs, proteasome inhibitors, and CD38- targeting monoclonal antibodies. These patients have a very short expected overall survival.

About Oncopeptides

Oncopeptides is a biotech company focused on research and development of pharmaceuticals for difficult-to-treat haematological diseases. The company uses its proprietary PDC platform to develop peptide-drug conjugated compounds that rapidly and selectively deliver cytotoxic agents into cancer cells. The first drug coming from the PDC platform, Pepaxto (INN melphalan flufenamide), was granted accelerated approval in the U.S., on February 26, 2021, in combination with dexamethasone, for treatment of adult patients with relapsed or refractory multiple myeloma. Due to regulatory hurdles the product is currently not marketed in the U.S. On June 23, 2022, CHMP adopted a positive opinion recommending full approval of Oncopeptides Pepaxti (melphalan flufenamide), in EU in patients with triple class refractory multiple myeloma. Oncopeptides is developing several new compounds based on the PDC platform. The company is listed in the Mid Cap segment on Nasdaq Stockholm with the ticker ONCO. More information is available onwww.oncopeptides.com.

This information was brought to you by Cision http://news.cision.com

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CHMP issues a positive opinion recommending full approval of Oncopeptides Pepaxti in EU for patients with triple class refractory multiple myeloma -...

Simple Anatomy of the Retina by Helga Kolb Webvision

By adminJune 29, 2022Stell Cell Research

Helga Kolb

1. Overview.

When an ophthalmologist uses an ophthalmoscope to look into your eye he sees the following view of the retina (Fig. 1).

In the center of the retina is the optic nerve, a circular to oval white area measuring about 2 x 1.5 mm across. From the center of the optic nerve radiates the major blood vessels of the retina. Approximately 17 degrees (4.5-5 mm), or two and half disc diameters to the left of the disc, can be seen the slightly oval-shaped, blood vessel-free reddish spot, the fovea, which is at the center of the area known as the macula by ophthalmologists.

A circular field of approximately 6 mm around the fovea is considered the central retina while beyond this is peripheral retina stretching to the ora serrata, 21 mm from the center of the retina (fovea). The total retina is a circular disc of between 30 and 40 mm in diameter (Polyak, 1941; Van Buren, 1963; Kolb, 1991).

The retina is approximately 0.5 mm thick and lines the back of the eye. The optic nerve contains the ganglion cell axons running to the brain and, additionally, incoming blood vessels that open into the retina to vascularize the retinal layers and neurons (Fig. 1.1). A radial section of a portion of the retina reveals that the ganglion cells (the output neurons of the retina) lie innermost in the retina closest to the lens and front of the eye, and the photosensors (the rods and cones) lie outermost in the retina against the pigment epithelium and choroid. Light must, therefore, travel through the thickness of the retina before striking and activating the rods and cones (Fig. 1.1). Subsequently the absorbtion of photons by the visual pigment of the photoreceptors is translated into first a biochemical message and then an electrical message that can stimulate all the succeeding neurons of the retina. The retinal message concerning the photic input and some preliminary organization of the visual image into several forms of sensation are transmitted to the brain from the spiking discharge pattern of the ganglion cells.

A simplistic wiring diagram of the retina emphasizes only the sensory photoreceptors and the ganglion cells with a few interneurons connecting the two cell types such as seen in Figure 2.

Fig. 2. Simple organization of the retina

When an anatomist takes a vertical section of the retina and processes it for microscopic examination it becomes obvious that the retina is much more complex and contains many more nerve cell types than the simplistic scheme (above) had indicated. It is immediately obvious that there are many interneurons packed into the central part of the section of retina intervening between the photoreceptors and the ganglion cells (Fig 3).

All vertebrate retinas are composed of three layers of nerve cell bodies and two layers of synapses (Fig. 4). The outer nuclear layer contains cell bodies of the rods and cones, the inner nuclear layer contains cell bodies of the bipolar, horizontal and amacrine cells and the ganglion cell layer contains cell bodies of ganglion cells and displaced amacrine cells. Dividing these nerve cell layers are two neuropils where synaptic contacts occur (Fig. 4).

The first area of neuropil is the outer plexiform layer (OPL) where connections between rod and cones, and vertically running bipolar cells and horizontally oriented horizontal cells occur (Figs. 5 and 6).

The second neuropil of the retina, is the inner plexiform layer (IPL), and it functions as a relay station for the vertical-information-carrying nerve cells, the bipolar cells, to connect to ganglion cells (Figs. 7 and 8). In addition, different varieties of horizontally- and vertically-directed amacrine cells, somehow interact in further networks to influence and integrate the ganglion cell signals. It is at the culmination of all this neural processing in the inner plexiform layer that the message concerning the visual image is transmitted to the brain along the optic nerve.

2. Central and peripheral retina compared.

Central retina close to the fovea is considerably thicker than peripheral retina (compare Figs. 9 and 10). This is due to the increased packing density of photoreceptors, particularly the cones, and their associated bipolar and ganglion cells in central retina compared with peripheral retina.

3. Muller glial cells.

Muller cells are the radial glial cells of the retina (Fig. 11). The outer limiting membrane (OLM) of the retina is formed from adherens junctions between Muller cells and photoreceptor cell inner segments. The inner limiting membrane (ILM) of the retina is likewise composed of laterally contacting Muller cell end feet and associated basement membrane constituents.

The OLM forms a barrier between the subretinal space, into which the inner and outer segments of the photoreceptors project to be in close association with the pigment epithelial layer behind the retina, and the neural retina proper. The ILM is the inner surface of the retina bordering the vitreous humor and thereby forming a diffusion barrier between neural retina and vitreous humor (Fig. 11).

4. Foveal structure.

The center of the fovea is known as the foveal pit (Polyak, 1941) and is a highly specialized region of the retina different again from central and peripheral retina we have considered so far. Radial sections of this small circular region of retina measuring less than a quarter of a millimeter (200 microns) across is shown below for human (Fig. 12a) and for monkey (Fig.12b).

The fovea lies in the middle of the macula area of the retina to the temporal side of the optic nerve head (Fig. 13a, A, B). It is an area where cone photoreceptors are concentrated at maximum density, with exclusion of the rods, and arranged at their most efficient packing density which is in a hexagonal mosaic. This is more clearly seen in a tangential section through the foveal cone inner segments (Fig. 13b).

Fig 13a. A) fundus photo of a normal human macula, optic nerve and blood vessels around the fovea. B) Optical coherence tomography (OCT) images of the same normal macular in the area that is boxed in green above (A). The foveal pit (arrow) and the sloping foveal walls with dispelled inner retina neurons (green and red cells) are clearly seen. Blue cells are the packed photoreceptors, primarily cones, above the foveal center (pit).

Below this central 200 micron diameter central foveal pit, the other layers of the retina are displaced concentrically leaving only the thinnest sheet of retina consisting of the cone cells and some of their cell bodies (right and left sides of Figs. 12a and 12b). This is particularly well seen in optical coherence tomography (OCT) images of the living eye and retina (Fig. 13a, B). Radially distorted but complete layering of the retina then appears gradually along the foveal slope until the rim of the fovea is made up of the displaced second- and third-order neurons related to the central cones. Here the ganglion cells are piled into six layers so making this area, called the foveal rim or parafovea (Polyak, 1941), the thickest portion of the entire retina.

5. Macula lutea.

The whole foveal area including foveal pit, foveal slope, parafovea and perifovea is considered the macula of the human eye. Familiar to ophthalmologists is a yellow pigmentation to the macular area known as the macula lutea (Fig. 14).

This pigmentation is the reflection from yellow screening pigments, the xanthophyll carotenoids zeaxanthin and lutein (Balashov and Bernstein, 1998), present in the cone axons of the Henle fibre layer. The macula lutea is thought to act as a short wavelength filter, additional to that provided by the lens (Rodieck, 1973). As the fovea is the most essential part of the retina for human vision, protective mechanisms for avoiding bright light and especially ultraviolet irradiation damage are essential. For, if the delicate cones of our fovea are destroyed we become blind.

The yellow pigment that forms the macula lutea in the fovea can be clearly demonstrated by viewing a section of the fovea in the microscope with blue light (Fig. 15). The dark pattern in the foveal pit extending out to the edge of the foveal slope is caused by the macular pigment distribution (Snodderly et al., 1984).

Fig. 16. Appearance of the cone mosaic in the fovea with and without macula lutea

If one were to visualize the foveal photoreceptor mosaic as though the visual pigments in the individual cones were not bleached, one would see the picture shown in Figure 16 (lower frame) (picture from Lall and Cone, 1996). The short-wavelength sensitive cones on the foveal slope look pale yellow green, the middle wavelength cones, pink and the long wavelength sensitive cones, purple. If we now add the effect of the yellow screening pigment of the macula lutea we see the appearance of the cone mosaic in Figure 16 (upper frame). The macula lutea helps enhance achromatic resolution of the foveal cones and blocks out harmful UV light irradiation (Fig. 16 from Abner Lall and Richard Cone, unpublished data).

6. Ganglion cell fiber layer.

The ganglion cell axons run in the nerve fiber layer above the inner limiting membrane towards the optic nerve head in a arcuate form (Fig. 00, streaming pink fibers). The fovea is, of course, free of a nerve fiber layer as the inner retina and ganglion cells are pushed away to the foveal slope. The central ganglion cell fibers run around the foveal slope and sweep in the direction of the optic nerve. Peripheral ganglion cell axons continue this arcing course to the optic nerve with a dorso/ventral split along the horizontal meridian (Fig. 00). Retinal topography is maintained in the optic nerve, through the lateral geniculate to the visual cortex.

Fig. 00. Schematic representation of the course of ganglion cell axons in the retina. The retinotopic origin of these nerve fibers is respected throughout the visual pathway. (Modified from Harrington DO, Drake MV. The visual fields. 6th ed. St. Louis: CV Mosby; 1990, with permission)

7. Blood supply to the retina.

There are two sources of blood supply to the mammalian retina: the central retinal artery and the choroidal blood vessels. The choroid receives the greatest blood flow (65-85%) (Henkind et al., 1979) and is vital for the maintainance of the outer retina (particularly the photoreceptors) and the remaining 20-30% flows to the retina through the central retinal artery from the optic nerve head to nourish the inner retinal layers. The central retinal artery has 4 main branches in the human retina (Fig. 17).

The arterial intraretinal branches then supply three layers of capillary networks i.e. 1) the radial peripapillary capillaries (RPCs) and 2) an inner and 3) an outer layer of capillaries (Fig. 18a). The precapillary venules drain into venules and through the corresponding venous system to the central retinal vein (Fig. 18b).

The radial peripapillary capillaries (RPCs) are the most superfical layer of capillaries lying in the inner part of the nerve fiber layer, and run along the paths of the major superotemporal and inferotemporal vessels 4-5 mm from the optic disk (Zhang, 1994). The RPCs anatomose with each other and the deeper capillaries. The inner capillaries lie in the ganglion cell layers under and parallel to the RPCs. The outer capillary network runs from the inner plexiform layer to the outer plexiform layer thought the inner nuclear layer (Zhang, 1974).

As will be noticed from the flourescein angiography of Figure 17, there as a ring of blood vessels in the macular area around a blood vessel- and capillary-free zone 450-600 um in diameter, denoting the fovea. The macular vessels arise from branches of the superior temporal and inferotemporal arteries. At the border of the avascular zone the capillaries become two layered and finally join as a single layered ring. The collecting venules are more deep (posterior) to the arterioles and drain blood flow back into the main veins (Fig. 19, from Zhang, 1974). In the rhesus monkey this perimacular ring and blood vessel free fovea is clearly seen in the beautiful drawings made by Max Snodderlys group (Fig. 20, Sodderly et al., 1992.)

The choroidal arteries arise from long and short posterior ciliary arteries and branches of Zinns circle (around the optic disc). Each of the posterior ciliary arteries break up into fan-shaped lobules of capillaries that supply localized regions of the choroid (Hayreh, 1975). The macular area of the choroidal vessels are not specialized like the retinal blood supply is (Zhang, 1994). The arteries pierce the sclera around the optic nerve and fan out to form the three vascular layers in the choroid: outer (most scleral), medial and inner (nearest Bruchs membrane of the pigment epithelium) layers of blood vessels. This is clearly shown in the corrosion cast of a cut face of the human choroid in Figure 21a (Zhang, 1974). The corresponding venous lobules drain into the venules and veins that run anterior towards the equator of the eyeball to enter the vortex veins (Fig. 21b). One or two vortex veins drain each of the 4 quadrants of the eyeball. The vortex veins penetrate the sclera and merge into the ophthalmic vein as shown in the corrosion cast of Figure 21b (Zhang. 1994).

8. Degenerative diseases of the human retina.

The human retina is a delicate organization of neurons, glia and nourishing blood vessels. In some eye diseases, the retina becomes damaged or compromised, and degenerative changes set in that eventally lead to serious damage to the nerve cells that carry the vital mesages about the visual image to the brain. We indicate four different conditions where the retina is diseased and blindness may be the end result. Much more information concerning pathology of the whole eye and retina can be found in a website made by eye pathologist Dr. Nick Mamalis, Moran Eye Center.

Age related macular degeneration is a common retinal problem of the aging eye and a leading cause of blindness in the world. The macular area and fovea become compromised due to the pigment epithelium behind the retina degenerating and forming drusen (white spots, Fig. 22) and allowing leakage of fluid behind the fovea. The cones of the fovea die causing central visual loss so we cannot read or see fine detail.

Glaucoma (Fig. 23) is also a common problem in aging, where the pressure within the eye becomes elevated. The pressure rises because the anterior chamber of the eye cannot exchange fluid properly by the normal aqueous outflow methods. The pressure within the vitreous chamber rises and compromises the blood vessels of the optic nerve head and eventually the axons of the ganglion cells so that these vital cells die. Treatment to reduce the intraocular pressure is essential in glaucoma.

Retinits pigmentosa (Fig. 24) is a nasty hereditary disease of the retina for which there is no cure at present. It comes in many forms and consists of large numbers of genetic mutations presently being analysed. Most of the faulty genes that have been discoverd concern the rod photoreceptors. The rods of the peripheral retina begin to degenerate in early stages of the disease. Patients become night blind gradually as more and more of the peripheral retina (where the rods reside) becomes damaged. Eventally patients are reduced to tunnel vision with only the fovea spared the disease process. Characteristic pathology is the occurence of black pigment in the peripheral retina and thinned blood vessels at the optic nerve head (Fig. 24).

Diabetic retinopathy is a side effect of diabetes that affects the retina and can cause blindness (Fig. 25). The vital nourishing blood vessels of the eye become compromised, distorted and multiply in uncontrollable ways. Laser treatment for stopping blood vessel proliferation and leakage of fluid into the retina, is the commonest treatment at present.

9. References.

Balashov NA, Bernstein PS. Purification and identification of the components of the human macular carotenoid metabolism pathways.Invest Ophthal Vis Sci.1998;39:s38.

Hageman GS, Johnson LV. The photoreceptor-retinal pigmented epithelium interface. In: Heckenlively JR, Arden GB, editors. Principles and practice of clinical electrophysiology of vision. St. Louis: Mosby Year Book; 1991. p. 53-68.

Harrington, D.O. and Drake, M.V. (1990) The Visual Fields, 6th ed. Mosby. St. Louis.

Hayreh SS. Segmental nature of the choroidal vasculature.Br J Ophthal.1975;59:631648.[PubMed] [Free Full text in PMC]

Henkind P, Hansen RI, Szalay J. Ocular circulation. In: Records RE, editor. Physiology of the human eye and visual system. New York: Harper & Row; 1979. p. 98-155.

Kolb H. The neural organization of the human retina. In: Heckenlively JR, Arden GB, editors. Principles and practices of clinical electrophysiology of vision. St. Louis: Mosby Year Book Inc.; 1991. p. 25-52.

Polyak SL. The retina. Chicago: University of Chicago Press; 1941.

Rodieck RW. The vertebrate retina: principles of structure and function. San Francisco: W.H. Freeman and Company; 1973.

Snodderly DM, Auran JD, Delori FC. The macular pigment. II. Spatial distribution in primate retina.Invest Ophthal Vis Sci.1984;25:674685.[PubMed]

Snodderly DM, Weinhaus RS, Choi JC. Neural-vascular relationships in central retina of Macaque monkeys (Macaca fascicularis).J Neurosci.1992;12:11691193.[PubMed]

Van Buren JM. The retinal ganglion cell layer. Springfield (IL): Charles C. Thomas; 1963.

Yamada E. Some structural features of the fovea centralis in the human retina.Arch Ophthal.1969;82:151159.[PubMed]

Zhang HR. Scanning electron-microscopic study of corrosion casts on retinal and choroidal angioarchitecture in man and animals.Prog Ret Eye Res.1994;13:243270.

Helga Kolb

Last Updated: October 8, 2011.

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Simple Anatomy of the Retina by Helga Kolb Webvision

Major Research Groupings | Institute Of Infectious Disease and …

By adminJune 29, 2022Stell Cell Research

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Secrets of Permanent Blindness Revealed by Stem-cell Research – The Epoch Times

By adminJune 29, 2022Stell Cell Research

Research into the retina and optic nerve using stem-cell models has unveiled specific genetic markers of glaucomathe worlds leading cause of permanent blindness possibly opening up new treatments for the condition.

Glaucoma is a blanket term describing a group of eye conditions that do damage to the retinal ganglion cellsneurons near the inner eye that make up the optic nerve. The optic nerve is the part of the eye that receives light and transmits it to the brain; thus, the damage that glaucoma does leads to permanent blindness. Thecondition is predicted to affect around 80 million people by 2040, yet treatments are extremely limited.

This study linked 97 genetic clusters to the damage done by the most common form of glaucoma, primary open-angle glaucoma or POAG, revealing important genetic components that control the way the condition attacks. POAG is a genetically complicated condition that is likely hereditary and, at the moment, cannot be stopped or reversed. The only treatment of POAG available involves releasing pressure on the eye, and this will only slow down the condition.

The research project was led jointly by the Garvan Institute of Medical Research, the University of Melbourne, and the Centre for Eye Research Glaucoma.

We saw how the genetic causes of glaucoma act in single cells, and how they vary in different people, said joint lead author of the study and Melbourne University academic, Prof. Joseph Powell, in a Garvan Institutemedia release.

Current treatments can only slow the loss of vision, but this understanding is the first step towards drugs that target individual cell types, Powell said.

The research behind the discoverywas published in the journalCell Genomicsand wasthe result of a lengthy collaboration between Australian medical research centres involving the investigation of complicated diseases and their underlying genetic causes, using stem-cell modelling; which the researchers said demonstrated the success of this study and the power of this approach.

Previously, glaucoma research was limited because samples of the optic nerve could not be obtained from participants in a non-invasive fashion. However, stem-cell modelling addressed this issue as it allowed researchers to develop optic nerve samples from skin, a much easier part of the body to extract.

The team administered skin biopsies on183 participants, 91 of whom had advanced primary open-angle glaucoma, to gather skin cells that they could reprogram to revert into stem cells and then guide into becoming retinal cells. Of the 183 samples collected, 110 samples, 54 from participants with POAG, were successfully converted from skin cells into retinal, and over 200,000 of these converted cells were sequenced to generate molecular signatures.

The researchers of this study employedsingle-cell RNA genetic sequencing in order to study individual cells. This form of sequencing creates an incredibly detailed genetic map, which looks for genetic variations that affect the expressionthe process of turning instructions from DNA into functional products like proteins of one or more genes. Through identifying these key genes, further deductions on the influence that genetic variations have on glaucoma can be made.

The signatures of those with and without glaucoma were compared to establish key genetic components that control the way that glaucoma attacks the retina.

The researchers first identified, using the signatures of both those with and without glaucoma,312 genetic variants associated with the ganglion cells that eventually degenerate in a person living with POAG. Further analysis of the genes associated with POAG linked the 97 clusters mentioned above to the damage done by glaucoma.

Another joint-lead author of the paper and Melbourne University professor, Alice Pebay, said that by studying glaucoma in retinal cells, a context-specific profile of the disease was created.

We wanted to see how glaucoma acts in retinal cells specificallyrather than in a blood sample, for instanceso we can identify the key genetic mechanisms to target, Pebay said.

Equally, we need to know which genetic variations are healthy and normal, so we can exclude them from a treatment.

To improve the understanding of complex conditions such as glaucoma, researchers noted it was important to establish a profile of the disease which promotesthe understanding of causes, risks and fundamental mechanisms of diseases. Furthermore, genetic investigations are critical to drug development and pre-clinical trials because they assist in constructing complete human models of diseases.

University of Tasmania professor and a third joint-lead author of the paper,Alex Hewitt said that the findings of this study set up future research into novel glaucoma treatments.

Not only can scientists develop more tailored drugs, but we could potentially use the stem-cell models to test hundreds of drugs in pre-clinical assays, said Hewitt.

This method could also be used to assess drug efficacy in a personalised manner to assess whether a glaucoma treatment would be effective for a specific patient.

Read more from the original source:
Secrets of Permanent Blindness Revealed by Stem-cell Research - The Epoch Times

Stem Cell Clinic

Stem Cell News

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