First generation stem cell therapies are simple in concept, a matter of transplanting cells taken from person A into person B in the hope of producing benefits, but the implementation hides a great deal of complexity. Tissue is provided by donors, cells are selected from that tissue, the resulting population of cells is expanded in culture, their behavior and state may be modified in simple ways via the addition of factors, the cells are manufactured into doses that can be frozen, and then injected into patients. For every one of those steps there are many, many different approaches, refinements, and epicycles.
It remains poorly understood as to why the outcomes of this class of therapy are so variable, even for clinics practicing what seem to be similar methodologies. It is hard to say why the (allegedly) more successful implementations are in fact more successful, particularly since most of them are owned by individual clinics and will never be the subject of formal clinical trials.
Near all such stem cell transplants reliably reduce chronic inflammation. This, at least, is fairly consistent across approaches. This outcome occurs due to signaling by the transplanted cells, and can last for months. The cells themselves near all die much more rapidly than that, though it is the case that a few clinics and approaches claim a meaningful degree of cell engraftment and survival. Beyond reductions in chronic inflammation, lasting improvement in tissue function or a regeneration of damaged tissue is a goal, but not one that is reliably achieved, considering this field as a whole.
A reduction in chronic inflammation makes age-related frailty an attractive target for stem cell therapies, characterized as it is by systemic inflammation. There is a great deal of evidence for continual inflammation to be an important cause of loss of muscle mass and strength, as well as the disruption of function in many other tissues. Thus a number of groups have attempted the expensive process of formalizing a stem cell therapy implementation in order to take it into clinical trials to treat frailty. Today's example appears modestly successful, though it is always worth comparing the outcomes of this sort of study with those that have been achieved via structured exercise programs and strength training regimens designed for the elderly.
Longeveron, a clinical stage biotechnology company developing cellular therapies for chronic aging-related and life-threatening conditions, today announced results from the Company's Phase 2b trial titled: A Phase 2b, Randomized, Blinded and Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Lomecel-B Infusion in Patients With Aging Frailty (the "Phase 2b trial"). Lomecel-B is a proprietary allogeneic product comprised of medicinal signaling cells (MSCs) from the bone marrow of adult donors and culture-expanded in Longeveron's current good manufacturing practice (cGMP) cell processing facility. The Phase 2b trial evaluated the safety and efficacy of a single peripheral intravenous infusion of four different doses of Lomecel-B cell therapy: 25 million (n=37), 50 million (n=31), 100 million (n=34) and 200 million (n=16) cells. Results were compared to placebo (n=30), on signs and symptoms of Aging Frailty, including mobility and exercise tolerance.
The main inclusion criteria for entry into the trial were subjects 70-85 years of age, a screening 6 minute timed walk distance of between 200 to 400 meters, a Canadian Health and Safety Assessment (CHSA) Clinical Frailty Scale score of 5 (mildly frail) to 6 (moderately frail), and a minimum serum TNF-α of ≥ 2.5 pg/mL. The primary analysis compared the change from baseline in six minute timed walk distance for the four Lomecel-B cohorts to the placebo cohort at Day 180. There were statistically significant increases in the highest 3 doses and no significant changes in the placebo or lowest dose of Lomecel-B (the following increases in 6 minute timed walk distance were observed: 25 million = 7.8 meters; 50 million = 35.8 meters; 100 million = 24.9 meters; 200 million= 49.3 meters; placebo = 8.0 meters).
"Improving physical function in older adults with frailty is one of the primary goals in geriatric medicine. The fact that patients enrolled in this study, with an average age of 75 and with clear mobility limitations, showed 6-month and 9-month placebo-adjusted increases in walking distance of 40 meters and 63 meters, respectively (at the 200 million cell dose), is significant for a number of reasons. Frailty is associated with poor clinical outcomes and high healthcare utilization and being able to improve and extend walking distance suggests preservation of function and potentially independence."