Urology Times is celebrating its 50th anniversary in 2022. To mark the occasion, we are highlighting 50 of the top innovations and developments that have transformed the field of urology over the past 50 years. In this installment, Melissa R. Kaufman, MD, PhD, FACS, discusses the innovative use of stem cellderived treatments in urologic conditions such as stress urinary incontinence. Kaufman is a Professor of urology, Patricia and Rodes Hart Endowed Chair of Urologic Surgery, and Chief of Reconstructive Urology and Pelvic Health at Vanderbilt University Medical Center, Nashville, Tennessee.

The newest frontier of therapy for stress incontinence is regenerative medicine and stem cellbased therapies. The basis of these are defined as embryonic stem cells or adult stem cells. Of course, there is continued scientific and ethical debate regarding the use of pluripotent embryonic stem cells. Our current cell-based therapies are somatic multipotent cells that are derived from adult tissues. These cells are terminally differentiated, and they serve in the body as progenitor cells for renewal of local tissues. These therapies have the potential to restore, in stress incontinence, the external striated sphincter, and potentially even smooth muscle within the bladder, neuromuscular transmission, as well as blood supply. There have been several different cell types that have been studied for this over the decadesboth animal and human studies include bone marrow cells, mesenchymal stem cells, adipose-derived cells, umbilical cord cells, [and] total nucleated cells, but the most well-studied population has been muscle-derived cells. This focuses on harvesting skeletal muscle, and it's delivered back to the external urethral sphincter after being expanded with the goal of regenerating this muscle and restoring function and, hopefully, continence.

The first successful clinical trial of autologous myoblast was used in the Austrian group in 2007. This was for female stress incontinence and was published in The Lancet.1 This was pioneering work well over a decade ago. Unfortunately, in 2008, that publication was retracted due to numerous concerns about the trial design and data interpretation.2 This setback undoubtedly resulted in a substantial delay in advancing this technology. However, at the 2021 AUA meeting, data were presented from a large randomized, double blind placebo-controlled trial of autologous muscle-derived cells, revealing really promising results for several subsets of stress incontinence patients, including those with persistent or recurrent incontinence following surgical interventions.

Stem cell technology is truly a transformational opportunity in urology, and the first regenerative option to complete really rigorous clinical evaluation. The autologous muscle-derived cell product are muscle progenitor cells [that] originate from tissue harvested from a muscle biopsy in the thigh and, upon injection, engraft into existing dysfunctional target tissue to improve muscle function. The product is in clinical trials for not just stress incontinence in females, but post-prostatectomy incontinence in men, fecal incontinence, underactive bladder, tongue dysphasia, and even cardiac applicationsbroad-ranging reach of a technology that is pioneered for a urologic indication. It's most studied, however, in stress incontinence. There have been over 500 women who have been treated with this product across several continents during all the iterations of the clinical trials. It augments urethral sphincter function and has the potential to be a really durable treatment. It produces some local tissue changes, but not systemic effects. Most of the subjects were in a broader stress incontinence treatment group. There was a sub population of women with a very troublesome condition of persistent or recurrent incontinence following prior surgical interventions. They demonstrated remarkable efficacy, with up to 30% having basically 0 to 1 stress leaks on their diaries in the trial. This was a very afflicted baseline with very phenomenal results. Because this was an unmet medical need and a very serious condition, this technology was granted expedited regenerative medicine advanced therapy designation by the FDA, which should really help facilitate future trials and bringing us to millions of patients who could benefit.

Stress incontinence has an enormous impact on a woman's quality of life. The gamut of this impact ranges beyond the direct symptoms, including an increased risk for depression and anxiety, reduced participation in physical activity and all the profound effects that can have, negative impacts on productivity at work, and the ability to maintain healthy sexual relationships. It leads to a substantial reduction in day-to-day functioning for women suffering from this disease. Recurrent or persistent incontinence for women who have undergone prior interventions is not short lived. It's not self-limiting, and [it] can progress in severity over time. This can cause additional stress. Women in this particular group have really limited options for treatment, that's not responded to what we consider gold-standard therapies for stress incontinence. Due to this wide range of an increasing number of patients and an aging population who suffer from stress incontinence, we really needed development of novel and effective therapeutic options with minimal patient morbidity, which was a paramount concern. We're embarking on the next frontier in urology with cellular therapies, and this is a gratifying opportunity to be practicing today, and have the ability to potentially provide durable, safe treatments that really reverse pathology and regenerate native tissue. The applications of this technology are very broad, and the next decade of innovations in this space will be astounding and transformative of our current treatment strategies for countless urology patients to improve both the quantity and quality of life.

References

1. Strasser H, Marksteiner R, Margreiter E, et al. Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial. Lancet. 2007;369(9580):2179-2186. doi:10.1016/S0140-6736(07)61014-9

2. Kleinert S, Horton R. Retraction--autologous myoblasts and fibroblasts versus collagen [corrected] for treatment of stress urinary incontinence in women: a [corrected] randomised controlled trial. Lancet. 2008;372(9641):789-790. doi:10.1016/S0140-6736(08)61320-3

See more here:
SUI treatment reaches "new frontier with regenerative medicine and stem cellbased therapies - Urology Times

Visit the News Hub

Blocking arginine metabolism leads to improved metabolic health, weight loss

An investigational cancer drug that starves tumors of their energy supply also shows evidence of improving whole body metabolism, according to a new study in mice from Washington University School of Medicine in St. Louis. Shown are sections of liver from mice on a high-fat, high-sugar diet. On the left, more white space indicates greater fat accumulation in an untreated mouse. On the right, in a mouse treated with the drug, the liver shows less fat accumulation.

An investigational cancer drug that starves tumors of their energy supply also shows evidence of improving whole body metabolism, leading to improved weight control, according to a new study in mice from researchers at Washington University School of Medicine in St. Louis.

The findings are published in the journal Cell Reports Medicine.

In a group of mice genetically prone to obesity and in a separate group of mice that became obese due to a high-fat, high-sugar diet, treatment with the drug ADI-PEG 20 increased insulin sensitivity, improved cholesterol levels, reduced fat buildup in the liver and lowered inflammation. For the mice genetically prone to obesity from birth, treatment with the drug protected them from their typical weight gain. And for the mice that became obese on a high-fat, high-sugar diet, treatment with the drug caused the mice to lose weight.

The drug is being investigated for potential use as a treatment for a number of cancers, including sarcoma, breast and pancreatic cancers. The drug breaks down the amino acid arginine in the blood, which deprives cancer cells of a key source of fuel. The researchers became interested in studying the drug after finding that genes responsible for breaking down arginine are dialed up tremendously when the body is in a fasting state. They wondered if the drug could mimic this effect of fasting.

Indeed, the researchers found that the drug triggers cells to undergo a process called autophagy, or self-eating, a cellular-level housecleaning process. Cells undergoing autophagy burn their own cellular waste products for fuel. During fasting, when no new fuel is coming from the outside, cells shift to autophagy, turning inward for their fuel supply.

Giving this drug seems to mimic some of the metabolic and therapeutic effects of fasting, said senior author Brian DeBosch, MD, PhD, an associate professor of pediatrics. I was surprised by how large the effect was. In the mice prone to weight gain, the group that received the drug ended up weighing about 25% less than the mice that didnt get the drug. And in the mice on the high-fat, high-sugar diet, we saw similar weight loss from the drug. Also, we dont think that the preponderance of the drugs metabolic benefits are from changes in body weight. In fact, for several outcome measures, the metabolic changes preceded significant changes in weight.

The drug has been tested in clinical trials investigating its safety and efficacy in treating several tumor types, including breast, prostate, pancreatic and liver cancers. In general, metabolic therapies tend to have fewer side effects and are safer than chemotherapy, radiation and even newer immunotherapies used to treat cancer.

DeBosch, a pediatric gastroenterologist who treats patients at St. Louis Childrens Hospital, said the research team would like to conduct a clinical trial of the drug to see if it triggers similar metabolic benefits and weight loss in people who are overweight or obese. One question that remains is whether the drug is safe to take long term. Its not a small molecule, like a statin, that can be taken for decades. The drug is a protein, so there is a possibility that patients could develop an immune response to it over time. However, DeBosch still sees a potential role for such a treatment over a matter of weeks to months.

Many patients with obesity who are considering bariatric surgery must first lose some weight to make the procedure safer, DeBosch said. It can be difficult for such patients to lose up to 10% of their body weight before the surgery. This type of therapy could potentially serve as a bridge to help patients lose weight before bariatric surgery, to reduce the risk of complications during and after the procedure.

This work was supported by the National Institutes of Health (NIH), grant numbers 1R01DK126622-01A1, 1R01HL147968-01A1, 1R21AT010520-01, UL1TR002345 and R56 DK115764; a Pilot Research Award from the American Association for the Study of Liver Disease; an AGA-Gilead Sciences Research Scholar Award in Liver Disease; the AGA-Allergan Foundation Pilot Research Award in Non-Alcoholic Fatty Liver Disease; the Washington University Digestive Disease Research Core Center, grant number P30DK52574; the Washington University Diabetes Research Center, grant number P30DK020579; the Nutrition & Obesity Research Center, grant number P30DK056341; the Association for Aging Research Junior Faculty Award; the Robert Wood Johnson Foundation; the Washington University Center for Autophagy Therapeutics Research; the Longer Life Foundation; and a Washington University School of Medicine Pediatric Gastroenterology Research Training Grant, number T32DK077653.

Part of this study was funded via a sponsored research agreement awarded by Polaris Pharmaceuticals. DeBosch holds two patents related to the work. Co-author Bomalaski is an employee of Polaris Pharmaceuticals Inc.

Zhang Y, Higgins CB, Van Tine B, Bomalaski JS, DeBosch BJ. Pegylated arginine deiminase (ADI-PEG 20) drives arginine turnover and systemic autophagy to dictate energy metabolism. Cell Reports Medicine. Jan. 18, 2022.

Washington University School of Medicines 1,700 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, and is among the top recipients of research funding from the National Institutes of Health (NIH). Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

More here:
Drug mimics beneficial effects of fasting in mice Washington University School of Medicine in St. Louis - Washington University School of Medicine in...

HOUSTON, Jan. 19, 2022 (GLOBE NEWSWIRE) -- Marker Therapeutics, Inc. (NASDAQ:MRKR), a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications, today announced that the United States Food and Drug Administration (FDA) Office of Orphan Products Development has granted Orphan Drug designation to MT-601, a multi-tumor-associated antigen (MultiTAA)-specific T cell product optimized for the treatment of patients with pancreatic cancer.

The FDAs orphan drug designation underscores MT-601s potential as a treatment for pancreatic cancer, a cancer typically diagnosed at an incurable advanced stage with a total overall 5-year survival rate of 10%, said Peter L. Hoang, President & CEO of Marker Therapeutics. Our novel therapy has shown encouraging results in an ongoing Phase 1 trial sponsored by Markers partners at the Baylor College of Medicine. In results reported at the 2020 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting, our therapy has demonstrated the potential to safely produce durable responses in combination with chemotherapy as a first-line treatment option for patients with advanced or metastatic pancreatic adenocarcinoma. The results also revealed that epitope spreading was consistent in responders to Multi-TAA-specific T cells. Following MT-401 for the treatment of post-transplant acute myeloid leukemia (AML), MT-601 is Markers second novel MultiTAA-specific T cell product to receive orphan drug designation and the first in a solid tumor indication, underscoring the potential of Markers multi-antigen targeting T cell therapy approach in both solid tumors and blood cancers.

Marker developed MT-601, a new product targeting six tumor-associated antigens (PRAME, NY-ESO-1, Survivin, MAGE-A4, SSX2, WT1) highly expressed in pancreatic cancer. The Company intends to initiate a Phase 1 multicenter study of MT-601 administered in combination with front-line chemotherapy to patients with locally advanced unresectable or metastatic pancreatic cancer. Marker designed the study to include an initial antigen escalation period followed by a dose escalation period and will enroll 20 25 patients for the study.

Story continues

The Company plans to file an Investigational New Drug Application (IND) for MT-601 for the treatment of pancreatic cancer in 2022.

Orphan designation is granted by the FDA Office of Orphan Products Development to advance the evaluation and development of safe and effective therapies for the treatment of rare diseases or conditions affecting fewer than 200,000 people in the U.S. Under the Orphan Drug Act, the FDA may provide grant funding toward clinical trial costs, tax credits, FDA user-fee benefits, and seven years of market exclusivity in the United States following marketing approval by the FDA. The granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. For more information about orphan designation, please visit the FDA website at http://www.fda.gov.

About Marker Therapeutics, Inc.Marker Therapeutics, Inc. is a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications. Markers cell therapy technology is based on the selective expansion of non-engineered, tumor-specific T cells that recognize tumor associated antigens (i.e. tumor targets) and kill tumor cells expressing those targets. This population of T cells is designed to attack multiple tumor targets following infusion into patients and to activate the patients immune system to produce broad spectrum anti-tumor activity. Because Marker does not genetically engineer its T cell therapies, we believe that our product candidates will be easier and less expensive to manufacture, with reduced toxicities, compared to current engineered CAR-T and TCR-based approaches, and may provide patients with meaningful clinical benefit. As a result, Marker believes its portfolio of T cell therapies has a compelling product profile, as compared to current gene-modified CAR-T and TCR-based therapies.

To receive future press releases via email, please visit: https://www.markertherapeutics.com/email-alerts.

IR and Media Contacts

Marker TherapeuticsNeda SafarzadehVice President/Head of Investor Relations, PR & Marketing(713) 400-6451investor.relations@markertherapeutics.com

Solebury TroutInvestorsXuan Yangxyang@soleburytrout.com

MediaAmy Bonannoabonanno@soleburytrout.com

Read the original post:
Marker Therapeutics Receives FDA Orphan Drug Designation for its Multi-Antigen Targeted T Cell Therapy for Pancreatic Cancer - Yahoo Finance

Researchers from the RCSI University of Medicine and Health Sciences, AMBER, the SFI Research Centre for Advanced Materials and BioEngineering Research along with leading global medical technology company Integra LifeSciences, have announced new breakthrough for nerve repair therapies based on bodys own processes in the journalMatrix Biology.

The pre-clinical study showed that use of extracellular matrix (ECM) supports improved nerve fibre regeneration across large nerve defects without the need for application of additional cells or growth factors. In these pre-clinical trials, the teams novel ECM-loaded medical device known as a nerve guidance conduit, was shown to support improved recovery responses at eight weeks following the repair of traumatic nerve lacerations with substantial loss of tissue.

The research team found that by fine-tuning the combination and ratio of ECM proteins and loading them into the nerve guidance conduit, it was possible to support increased pro-repair inflammation, increased blood vessel density, and increased density of regenerating nerves, all as compared to standard of care. By mimicking the bodys nerve repair processes, this new approach may eliminate the need for additional stem cells and drug therapies.

Peripheral nerve injury is a major clinical problem and is known to affect more than 5 million people worldwide every year, leaving those afflicted with loss of motor or sensory function to muscles or skin. Current therapies to repair nerve damage involve transplanting the patients healthy nerves to repair damage or implanting an artificial nerve guidance conduit. The teams novel patented approach to nerve repair has been shown to increase the density of regenerating long-nerve structures, known as axons, and to generate a strong increase in blood vessel density to better support the regenerating tissues.

Commenting on the results, lead authors Drs. Alan Hibbitts and Zuzana Ko from the Tissue Engineering Research Group based at Dept. of Anatomy and Regenerative Medicine at RCSI, and AMBER, said:

In our lab-based trials, we discovered that at eight weeks post implantation our nerve guidance conduit had successfully improved the prognosis for nerve regeneration and repair over the current clinical gold standard. Our conduit supported clear improvements in nerve repair and blood vessel formation and most importantly, we saw that we could scale this up to approach very large nerve defects in our pre-clinical studies.

Regarding the success of this study, Prof. Fergal OBrien, Principal Investigator on the project and Professor of Bioengineering and Regenerative Medicine, Head of Tissue Engineering Research Group at RCSI and Deputy Director of AMBER, said the partnership between RCSI, AMBER and Integra LifeSciences was critical to ensure clinical relevance and a pathway from lab to patient.

Working with Integra Chief Scientist, Dr. Simon Archibald, the research had a clear focus to create a device based on scientific excellence with improved outcomes that would translate well through regulatory assessment, into the clinical setting, and ultimately, patients. This provides a more direct route to market and therefore the potential for faster real-world impact in improving patient quality of life.

Dr Simon Archibald, Chief Scientist at Integra LifeSciences added: We have partnered with Prof. Fergal OBrien and his team at RCSI to innovate new solutions in regenerative medicine since 2005, and over that time, we have rapidly accelerated the development and translation of new biomaterials. We are enthusiastic for the future potential of this iterative innovation to address long-gap nerve repair, building on our current leading clinical materials for short-gap nerve repairs. Placing Integra at the coalface of research enables us to bring our expertise to the heart of the scientific process and identify clinically relevant solutions based on cutting-edge science, to improve patient outcomes and the most efficient pathway from the lab to clinical setting.

Detailing his teams plans, Professor OBrien said: Our new ECM-enhanced nerve guidance conduits are part of my teams ongoing research to address long peripheral nerve defects in partnership with Integra LifeSciences. The outputs from this project will address increasingly challenging nerve defect distances with the ambition to relieve the current clinical reliance on grafted nerves and move into the next phase of pre-clinical trials. Our partnership with Integra LifeSciences has been essential to this process, and we look forward to an ambitious programme of work that will advance continued enhanced treatments for nerve damage and injury.

Reference: Hibbitts AJ, Ko Z, Kneafsey S, et al. Multi-Factorial Nerve Guidance Conduit Engineering Improves Outcomes in Inflammation, Angiogenesis and Large Defect Nerve Repair. Matrix Biology. Published online January 13, 2022. doi:10.1016/j.matbio.2022.01.002

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Continue reading here:
Researchers Harness the Cell Matrix To Repair Nerves - Technology Networks

NOW IS THE TIME TO SUPPORT REGENERATIVE MEDICINE

TORONTO, Jan. 19, 2022 /CNW/ - As The Government of Ontario prepares its 2022 Spring Budget, OIRM is raising awareness of the massive losses expected if critically important sector funding is not continued.

At OIRM, we understand the unprecedented financial challenges facing Ontario, particularly in the healthcare sector, and this makes it even more vital that we take full advantage of the vast potential of Ontario's newly established Regenerative Medicine ecosystem to address Finance Minister Bethlenfalvy's key priorities:

Ontario's innovative stem cell scientists are already saving lives, including state-of-the-art treatments for COVID recovery, as Sharon Charlebois can attest. After being admitted into ICU with COVID-19 at The Ottawa Hospital, Sharon attributes her survival to the stem cell treatment she received. Read Sharon's fully story here.

Stem cell science originated in Toronto 50 years ago with the ground-breaking discovery by Doctors James Till and Ernest McCulloch; a remarkable contribution to our provincial, and national, legacy.

At a time when the unprecedented commercial value of stem cell technologies are just beginning to be realized, Ontario's stem cell innovators are now at a crossroads. Without ongoing funding, Ontario stands to lose it competitive advantage and the opportunity to benefit from the burgeoning Regenerative Medicine commercial sector.

Catalyzed by an initial $25M investment from the provincial government in 2015, OIRM has since generated $174.5M (6.9-fold ROI) in leveraged funding and invested in cutting-edge technologies that generated an additional $332M (13-fold ROI) in Series A investment. OIRM support was a key factor in the path leading to the creation of BlueRock Therapeutics, one of the greatest Canadian biotech success stories, which was acquired by Bayer in 2019 for $1B (40-fold ROI) and is now a leading engineered cell therapy company.

Story continues

"BlueRock invested in the Ontario ecosystem because of work that OIRM had supported from Dr. Michael Laflamme (UHN). It was really the strength of the science under OIRM's guidance, in my view, that led to our decision to launch and build BlueRock Therapeutics in the Toronto-area. OIRM's support was critical to getting a small biotech launched. I would like to see that funding envelope increased to give the Institute the ability to bring these programs to a later phase of value creationsomething that would have the added benefit of creating more confidence in potential investors."- Dr. Bob Deans, Chief Technical Officer, BlueRock Therapeutics 2017-2020

It is reasonable to expect more opportunities like BlueRock to develop if Ontario continues to nurture stem cell research and innovation. Ontario is staring at a $1B economic opportunity by funding Regenerative Medicine advancements. But in 2020, while the California Institute for Regenerative Medicine was refunded at $5.5B USD, here at home the funding for OIRM was removed as part of a cost-cutting exercise, and unfortunately before a glowing report from a blue-ribbon international review panel that recommended renewed funding for OIRM.

OIRM is imploring government to reconsider its position and continue funding stem cell advancements in Ontario. An investment of $25M over 5 years will yield massive returns for Ontario.

At no point in history have public health and economic recovery been simultaneously prioritized by the provincial government as urgently as right now. Medical treatments are evolving rapidly, and if made-in-Ontario stem cell research remains a priority for The Government of Ontario, there is good reason to feel hopeful about the future.

OIRM is a passionate champion for healthcare providers and their patients as we build a healthier future for Ontario, Canada, and the world.

SOURCE Ontario Institute for Regenerative Medicine

Cision

View original content: http://www.newswire.ca/en/releases/archive/January2022/19/c9589.html

Original post:
Ontario Institute for Regenerative Medicine (OIRM) - Urgent Appeal to The Government of Ontario - Yahoo Canada Finance