CRATUS Clinical Trials: MSCs And Frailty

Longeveron is sponsoring FDA authorized, placebo controlled clinical trials with open enrollment at several leading hospitals and medical centers across the nation for the following conditions: The Metabolic Syndrome; Alzheimer’s Disease; and Aging Frailty. Longeveron has also gained approval from the National Stem Cell Ethics Committee in the Bahamas to have single-arm Treatment Registries for the following conditions: Aging Frailty; Frailty for reasons other than aging; Musculoskeletal Injury Due to Overuse or Athletics; Alzheimer’s Disease/Cognitive Impairment; and Osteoarthritis. 

Stem cells used in American clinical trials and those in the Bahamas are the same. Treatment is an intravenous infusion, plus a direct intra-articular injection for Osteoarthritis indications, which take 45 minutes while the patient is resting in a chair. Longeveron is working to develop biological solutions to treat difficult chronic and life threatening conditions by testing MSCs using its proprietary LMSCs which are derived from young healthy adult donor bone marrow, and are multipotent regenerative and restorative cells that may help to modulate the immune system. These cells have powerful anti-inflammatory properties and will target sites of inflammation, injury, and disease where they will secrete bioactive molecules to stimulate the body’s own stem cells to aid in repairing damage and promote endogenous tissue repair. 

The CRATUS Study Phase1 and Phase 2 are both published in the journal Gerontology. These were early phase trials designed to measure safety and efficacy of LMSCs that provided striking results and paved the way for larger randomized clinical trials. “In these studies we came up with the idea that infusions of (Longeveron) Allogeneic Mesenchymal Stem Cells which come from a donor could be used to treat the aging frailty syndrome.” 

Frailty affects between 7-12% of those aged 65+. It is characterized by increased inflammation that worsens with age, contributes to a weakened immune system, fatigue, weakness, weight loss, slowness, difficulty with day to day life, decreased physical function and mobility, as well as general decreases in health and well being all leading to dependency, hospitalization, disability, and death. Chronic inflammation drives progression of most age related conditions, and high levels are considered to be a major component of the frailty syndrome. 

“The aging frailty syndrome is a very common problem among older individuals that leads to an increased vulnerability to adverse health outcomes, and diminishes their functional capacity, making it harder for them to perform basic activities of daily living like walking, taking care of themselves, or even driving a car. This is a very important geriatric syndrome, treating it could have a major impact on healthspan, particularly in aging societies like ours and societies with increased longevity.”

With age endogenous stem cell production decreases which likely contributes to the reduced ability to regenerate and repair organs and tissues. Regenerative treatment may help to ameliorate the symptoms of frailty, and extend the health and ability of a patient to regenerate functionality. MSCs are known to target sites of injury and inflammation to assist in cellular repair, making them an ideal candidate for frailty. 

“In our study we did a randomized infusion of either cells or a placebo to 30 eligible patients who had aging frailty with the average age of 75. The study measured a host of different outcomes that will measure the aging frailty syndrome such as pulmonary function, 6 minute walking distance, and markers of inflammation. There were significant improvements in the group that received the cells and not the placebo.” Treated groups safely experienced remarkable improvements in physical performance measures and inflammatory biomarkers that characterize the aging frailty syndrome.

Building on the very promising results from the smaller studies the researchers are moving on to a larger, double blind, placebo controlled trial to confirm outcome on a greater scale. “This study is being conducted under the National Institute for Aging funding here in the U.S at about 10 centers across the nation including the Veterans Administration Hospital. American Veterans of foreign wars are important to America not only because of the service they provided but because this important group has a very high burden of aging related diseases and a very high burden of frailty. Geriatric studies at the VA are very important and they are a big contributor to the new study which is nearly completed enrolling, and we expect to have results next year.”

“This study will enroll 150 patients, with this study in hand, it will provide a lot more information about the correct dosing, the correct patient population, and a validation of those outcome parameters.” 

This is a promising and innovative approach for the treatment of frailty, we look forward to results from further groundbreaking trails. It is possible that a single treatment with few if any adverse effects may help to provide significant improvements that are sustained for many months. To find out more about Longeveron, their research, or to get information about participating in a trial you can go to the website or click here.