Longeveron developing stem cell treatments for Frailty, Alzheimers and other aging diseases

Longeveron is a life sciences company developing biological solutions for aging and aging-associated diseases through the use of Allogeneic Human Mesenchymal Stem Cells, harvested and grown at our facility in Miami, Florida, from adult-donor bone marrow. Longeveron is a privately funded startup. The Longeveron-grown Mesenchymal Stem Cells (LMSCs) are multipotent stem cells.

Mesenchymal stem cells, or MSCs, are multipotent stromal cells that can differentiate into a variety of cell types, including: osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue). MSC have been found in organisms (in-vivo) and have been studied as well in tissue culture (in-vitro).

Nextbigfuture interviewed Dr. Joshua Hare, Longeveron Chief Science Officer. Dr. Joshua Hare co-founded Longeveron in 2014 utilizing intellectual property and technology exclusively licensed from the University of Miami, where he is also the founding Director of the university’s Interdisciplinary Stem Cell Institute (ISCI).

Longeveron sees patients getting once a year intravenous infusions of needed stem cells.
Healthy adult stem cells are from bone marrow donations. Cells undergo cultured expansion by a billion times.
This enables one donation to be used for hundreds of treatments.
They are not using telomerase but using the culturing conditions to control the health and potency of the stem cells.

Longeveron will be improving the culturing expansion and foresee being able to eventually have an unlimited supply of stem cells. This will eventually mean that they will not be dependent on stem cell donations.

Longeveron also has a vision of improving the potency of the stem cells so that a smaller dose would be needed to achieve the same effect.

Longeveron seeks to improve the health and healthspan of people by addressing Frailty, Alzheimers, Metabolic syndrome and many other diseases.

Frailty trial

Patients before the Longeveron stem cell treatment walked an average of 375 meters in 6 minutes before the Longeveron cell treatment.
After stem cell treatment they walked 70 meters further in 6 minutes. This is an average of 445 meters in 6 minutes.

Aging Frailty is estimated to affect over 10% of people 65 years of age and older. Aging Frailty results in increased fatigue, difficulty going about daily activities, decreased mobility, heightened risk of injury from falling, more frequent visits to the doctor and a general decrease in health without a definitive explanation of the cause.

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 (immunosenescence).

Mesenchymal stem cell therapy can alleviate inflammation, and promote endogenous tissue repair. We thus believe that LMSCs can be therapeutically beneficial to those with Aging Frailty, with long-term benefits of promoting increased mobility, strength and stamina, while also improving the immune systems and, ultimately, overall quality of life. We are currently the only organization running clinical trials using stem cells to affect the symptoms of Aging Frailty.

A Phase 2b, Randomized, Blinded and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Longeveron Allogenic Human Mesenchymal Stem Cell Infusion in Patients With Aging Frailty

Frailty is a common aging-related medical syndrome with multiple causes and contributors, characterized by diminished strength, endurance, and reduced physiologic function. Frail individuals have an increased risk of poor clinical outcomes such as hospitalization, dependency, disability and/or death. Signs and symptoms of frailty include reduced activity, slowness, involuntary weight loss, weakness, and fatigue. Additionally, there is a connection between frailty and chronic inflammation in the body. Frail elderly patients place significant demand for healthcare services and there are no approved therapeutics for the syndrome. It is widely believed that frailty can be reversed, and in this regard there is a major need for a safe and effective treatment.

An individual’s endogenous stem cell production decreases with age; this decrease likely contributes to the reduced ability to regenerate and repair organs and tissues. It is predicted that regenerative treatment could ameliorate symptoms of frailty, and potentially extend the health and ability of a patient to regenerate functionality. Human Mesenchymal Stem Cells are known to home to sites of injury, reduce inflammation, and assist in cellular repair, thus could be an ideal candidate for frailty. The purpose of this study is to measure the safety and efficacy of Longeveron Allogeneic Mesenchymal Stem Cells in patients with aging frailty.

The first study was a Phase I open-label trial (20) where allogeneic MSC collected from the bone marrow of younger donors aged 20–45 years were used to treat 15 frail patients (average age 78 years) using a single infusion of either 50, 100, or 200 million cells. After 6 months, outcomes that improved included the 6-minute walk and tumor necrosis factor α (TNFα) levels, with variable improvements in forced expiratory volume in 1 second (FEV1), Mini-Mental State Examination (MMSE), and quality of life. No significant adverse effects were recorded, and only one patient developed antibodies that could potentially neutralize the outcomes.

The second study by the same group was a Phase II randomized, double-blinded trial of allogeneic MSC at two doses (100 or 200 million cells) versus placebo (21). The participants were 30 frail patients with an average age of 76 years. No therapy-related adverse effects were documented at 1 month. Improvements were reported for physical performance, the 6-minute walk test, short physical performance exam, FEV1, and TNFα mostly in the 100 million cell groups.

Alzheimer’s Trial

Allogeneic Human Mesenchymal Stem Cell Infusion Versus Placebo in Patients With Alzheimer’s Disease.

Alzheimer’s disease is a neurodegenerative disorder that leads to progressive memory loss and death. An estimated 5.3 million Americans are currently diagnosed, but there are few drugs available for treating Alzheimer’s disease, and none that affect the long-term progression of the disease. (Alzheimer’s Association ) Barring significant medical breakthroughs, as many as 16 million Americans could be afflicted by the year 2050.

An important component in the progression of Alzheimer’s disease is neuroinflammation. 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.

Alzheimer’s disease is a neurodegenerative disorder that leads to progressive memory loss and death. This is a Phase I, prospective, randomized, placebo-controlled, double-blinded study designed to test the safety and efficacy of LMSCs (Longeveron Mesenchymal Stem Cells) for the treatment of subjects with clinically diagnosed Alzheimer’s disease.

Primary Outcome Measure:
To demonstrate the safety of LMSCs administered to subjects with Alzheimer’s disease.
Secondary Outcome Measure:
Preliminary efficacy will be determined by examining for changes in Alzheimer’s disease status and rate of decline as assessed by factors outlined in the complete study description.

NIH funding for Metabolic Syndrome

Longeveron has been awarded a 1.15 million NIH grant to develop their Metabolic syndrome stem cell treatment.

The current grant represents the third funding award for Longeveron, which has previously received financial support from the Alzheimer’s Association and Maryland’s TEDCO for clinical trials in Alzheimer’s disease and Hypoplastic Left Heart Syndrome, respectively.

An estimated 1 in 3 American adults live with Metabolic Syndrome every day. Obesity, high blood pressure, and/or increased blood glucose contribute to the risk, and the syndrome can lead to coronary heart disease, stroke, diabetes and — in some cases — even death.

Physicians often recommend diet, exercise and other lifestyle changes as part of a treatment plan. The goal is to help people lose weight, stay physically active and get more engaged in their health and wellness. But committing to significant behavioral change remains challenging for many people with Metabolic Syndrome, often long after New Year’s resolutions dissolve.

The company’s investigators plan to use the research award to conduct Phase 1 and 2 clinical trials of Longeveron mesenchymal stem cells (LMSCs) to improve the outlook for people with Metabolic Syndrome. LMSC therapy represents a much-needed novel approach — targeting the drivers of Metabolic Syndrome at a cellular level. The company will study Metabolic Syndrome in connection with Aging Frailty, a clinically defined wasting syndrome that increases vulnerability to morbidity, injury and death. There is a high incidence of Metabolic Syndrome among Aging Frailty subjects, and both are characterized by a pro-inflammatory state which LMSCs are intended to reduce.