Feb 28, 2019
Biotech Company Seeks Volunteers For Stem Cell Trials On Age-Related Diseases Including Alzheimer's
Robin Seaton Jefferson

https://www.forbes.com/sites/robinse.../#4a4583393cc1

A Florida-based biotech and regenerative medicine company is progressing with clinical research studying the safety and efficacy of stem cell treatments for aging-related diseases. Longeveron is currently recruiting for an Alzheimer’s stem cell clinical trial, as well as one study examining stem cells to boost flu vaccine immune response in older patients and another expanding its work on Aging Frailty.

Currently there are no FDA-approved stem cell treatments in the United States, aside from those therapies approved for bone marrow transplants to treat conditions of the blood such as leukemia, sickle cell anemia and some metabolic conditions.. But Longeveron, along with Samuel Golpanian, M.D. and other researchers at the University of Miami (UM) Miller School of Medicine, has already published two clinical studies of stem cell treatments for Aging Frailty.

Located in the University of Miami Life Science & Technology Park (LSTP) in Miami, Florida—Longeveron produces and tests an allogeneic mesenchymal stem cell product “LMSCs” for use in aging and aging-associated diseases. The LMSCs are produced at the company’s facility from healthy adult-donor bone marrow. Through its work, Longeveron says it seeks to improve what it calls “healthspans” – health and quality of life at the later stages of life.

The world’s population is aging. In fact, the number and proportion of older people are growing in nearly every country in the world. And population aging, according to the United Nations, “is poised to become one of the most significant social transformations of the twenty-first century, with implications for nearly all sectors of society, including labor and financial markets, the demand for goods and services, such as housing, transportation and social protection, as well as family structures and inter-generational ties.”

The World Population Prospects: the 2017 Revision projects that the number of older persons — those aged 60 years or over — is expected to more than double by 2050 and to more than triple by 2100, “rising from 962 million globally in 2017 to 2.1 billion in 2050 and 3.1 billion in 2100. Globally, population aged 60 or over is growing faster than all younger age groups.”

In response, Longeveron is currently seeking participants for three studies they hope will lead to new treatments for a number of diseases that plague older adults. Working with grants from the National Institutes of Health (NIH), the Maryland Technology Development Corp. (TEDCO) and the Alzheimer’s Association, the company’s trials are being conducted pursuant to Investigational New Drug Applications (IND) in conformance with U.S. Food & Drug Administration (FDA) regulations.

In 2017, Longeveron and UM's Miller School of Medicine published results of Phase I and Phase 2 clinical studies in the Journals of Gerontology that evaluated the safety and efficacy of allogeneic MSC infusion in patients with aging frailty, a serious geriatric syndrome that can lead to other severe health conditions, such as heart disease. Allogeneic MSCs were tested in the Phase I/2 proof-of-concept studies conducted by investigators at the University of Miami's Miller School of Medicine. According to the publication, allogeneic MSCs were shown to be safe and well-tolerated in frail, elderly subjects in those studies.

Longeveron is now recruiting for an expanded Phase 2b Aging Frailty study as well as for a Phase 1 Alzheimer’s trial, and Phase 1 and 2 trials to evaluate the safety and efficacy of its stem cells for improving flu vaccine immune response in aging frailty patients.

“Stem cell therapy is a promising new treatment option under clinical study for chronic diseases and injuries affecting various organ systems,” said Geoff Green, Senior Vice President of Clinical Operations at Longeveron. “One of the most exciting ideas emerging from the field of regenerative medicine is the theory that stem cells may prevent, treat or possibly even reverse aging-related disability and frailty. Because stem cells migrate to sites of tissue injury and inflammation, there is significant interest in research to understand the ability for cells to reduce inflammation, repair tissue, and improve or restore functional capacity and ameliorate diseases and disorders associated with aging.”

Green said currently there are no FDA-approved stem cell treatments in the United States, aside from those therapies approved for bone marrow transplant, also known as hematopoietic stem cell transplant. These therapies treat conditions of the blood such as leukemia, sickle cell anemia and some metabolic conditions. According to Longeveron’s website, “Doctors have been transferring blood stem cells by bone marrow transplant for more than 40 years. Advanced techniques for collecting or “harvesting” blood stem cells are now used. Cord blood, like bone marrow, is stored as a source of blood stem cells and is used as an alternative to bone marrow in transplantation. Other stem cell applications are the use of skin progenitor cells for burns and the use of limbal stem cells, which reside in the cornea, for injury of the cornea. With the exception of the treatments discussed here, the use of cell therapies remains at an experimental stage.”

Green said the company’s US clinical studies are conducted under the approval of the FDA per Investigational New Drug (IND) applications, “meaning we are held to and comply with strict regulatory requirements," he said. "This is intended to give patients and physicians confidence that the product is made according to the existing standards in place that regulate the clinical testing of allogeneic stem cells. We hope to be the first to offer an FDA-approved off-the-shelf stem cell product as a treatment for conditions such as Aging Frailty, Alzheimer’s disease and Metabolic Syndrome.”

The U.S. Food and Drug Administration (FDA) recently upped its oversight and enforcement on stem cell researchers with substantial warnings and new regulations.

“Stem cells have been called everything from cure-alls to miracle treatments. But don’t believe the hype,” the FDA declared to the world on its site in 2017. “Some unscrupulous providers offer stem cell products that are both unapproved and unproven. So beware of potentially dangerous procedures—and confirm what’s really being offered before you consider any treatment.”

Here is what scientists do know about stem cells and potential therapies, according to the FDA:

Stem cell therapies may offer the potential to treat diseases or conditions for which few treatments exist.
Sometimes called the body’s “master cells,” stem cells are the cells that develop into blood, brain, bones and all of the body’s organs.
Stem cells have the potential to repair, restore, replace and regenerate cells, and could possibly be used to treat many medical conditions and diseases.
Still in response to its concerns that some patients seeking cures and remedies were becoming increasingly vulnerable to illegal and potentially harmful stem cell treatments, the nation’s public health watchdog, two years ago, said it, “increased its oversight and enforcement to protect people from dishonest and unscrupulous stem cell clinics, while continuing to encourage innovation so that the medical industry can properly harness the potential of stem cell products.”

For more information on the FDA’s warnings, click here. For more information on cellular and gene therapy products approved by the FDA, click here.

Longeveron defines Aging Frailty as “an aging-related condition that leads to a high risk for adverse health outcomes such as falls, debilitation, loss of independence, susceptibility to infection, institutionalization, hospitalization and death.”

Green said scientists at Longeveron believe an underlying trigger thought to be critically involved in Aging Frailty is chronic low-grade inflammation within the body. “Such chronic inflammation can take severe tolls on the body and general health. This includes weakening of the immune system or immunosenescence,” he said. “Mesenchymal stem cell therapy can alleviate inflammation, and promote endogenous tissue repair. We thus believe that LMSCs could potentially be therapeutically beneficial to those with Aging Frailty, and we are measuring the effect of the cells on functional endpoints such as mobility, strength, endurance and balance, and the patient’s opinion of their quality of life.”

These endpoints, Green said, are known to be predictive of long-term clinical outcomes, “so there is great interest in learning the effect in the target patient population using randomized, placebo-controlled clinical trials. To our knowledge, we are currently the only organization conducting clinical trials using allogeneic mesenchymal stem cells in Aging Frailty.”

An important component in the progression of Alzheimer’s disease is neuroinflammation, Green said. “Given the abilities of mesenchymal stem cells to reduce inflammation and promote regeneration, LMSCs are being clinically evaluated in the treatment of Alzheimer’s disease. Prior studies in mouse models of Alzheimer’s disease support this approach.”

Mayo Clinic describes Metabolic Syndrome (MetS) as "a cluster of conditions — increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels — that occur together, increasing your risk of heart disease, stroke and diabetes." Age, race, obesity, diabetes and other conditions such as cardiovascular disease, nonalcoholic fatty liver disease or polycystic ovary syndrome can increase a persons' risk of having MetS. Conversely, having metabolic syndrome can increase a person's risk of developing diabetes and cardiovascular disease, Mayo says.

“Allogenic human mesenchymal stem cells, such as LMSCs have been shown to inhibit inflammation, upregulate anti-inflammatory pathways and restore endothelial function,” Green said. “Our hypothesis holds that therapeutic intervention aimed at restoration of endothelial function and lowering certain inflammatory cytokines could potentially reduce the risk of developing Type II Diabetes Mellitus and vascular events. This could be of tremendous value. It is estimated that over 40% of adults in the U.S. have MetS, making consequences of the condition an enormous strain on the population and our healthcare system.”

Robin Seaton Jefferson lives just outside of St. Louis with her husband of 25 years and two daughters. Find her on Twitter and Facebook @SeatonJefferson or contact her at rsjreporter@charter.net.