The first results of two human clinical trials using stem cell therapy for age-related frailty have been published, and the results are very impressive indeed. The studies show that the approach used is effective in tackling multiple key age-related factors.

Aging research has made significant progress in the last few years, with senescent cell clearing therapies entering human trials this year, DNA repair in human trials, and a number of other exciting therapies nearing human testing. We are reaching the point where therapies that target aging processes are no longer a matter of speculation; they are now an undeniable matter of fact.

What are mesenchymal stem cells?

Mesenchymal stem cells (MSCs) are one of the most commonly used types of stem cells in therapy. MSCs are adult stem cells that can become other types of cells, depending on stimulus; this ability to become a variety of other cell types is known as multipotency[1].

The cells into which MSCs can transform (differentiate) include osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells), and adipocytes (fat cells). MSCs are of great interest to aging researchers and are arguably one of the most well studied and understood types of stem cells[2].







MSCs are currently in various trials to treat conditions such as cancer, heart disease, and arthritis[3]. The potential of MSCs for treating neurodegenerative diseases, such as Alzheimer’s, are also being explored in preclinical testing[4-5].

A therapy for age-related frailty

The focus of the MSC therapy in the case of these two clinical trials is to reduce the effects of age-related frailty on senior citizens. This also marks an important step for rejuvenation biotechnology, as this is the first stem cell treatment that is close to final FDA approval for specifically targeting age-related frailty. Should this be approved, then it opens the door for other similar approaches and the potential treatment of many age-related diseases.

The therapy itself uses MSCs taken from adult donor bone marrow and is infused into patients with an average age of 76 years old. The good news is that patients in both the phase 1 and phase 2 clinical trials have shown no adverse effects to treatment.

This is excellent news and now paves the way to move to phase 3 clinical trials, which are larger-scale tests to further determine the efficacy and compare it to the best currently available treatments, for which there are basically none beyond simple coping approaches, such as walking sticks and frames to compensate for frailty.







It is also important to note that at this at this point, the drug or therapy is accepted as having some effect. You can read more about the clinical trial process and what each phase means here.

In the first trial, 15 patients with age-related frailty were given a single transplant of MSCs from donors aged between 20 and 45[6]. Six months later, all patients in the trial showed an improved level of fitness, lower levels of inflammatory tumor necrosis factor (TNF), and improved quality of life in general. TNF is one of the regulators of inflammation and contributes to the chronic age-related inflammation known as “inflammaging”, which drives a number of age-related diseases[7].

The second trial was a randomized, double-blind study including a placebo group. An improved physical performance level was observed in patients, and, again, the level of systemic TNF, and thus inflammation, was reduced[8]. Once again, there were no adverse effects observed in the patients, and the researchers wrote:

Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome.

David G. Le Couter and colleagues have written about the clinical trials in a guest editorial in The Journals of Gerontology:

There are always caveats associated with interpreting efficacy in small numbers of subjects, yet it is remarkable that a single treatment seems to have generated improvement in key features of frailty that are sustained for many months

The next step for the researchers here is to begin a phase 2b clinical trial with 120 patients in ten different locations. Following the conclusion of this, a large randomized phase 3 trial will be launched, and this will be the final barrier to public approval for the therapy.







Conclusion

With an ever-increasing number of aged people in our population, stem cells hold great potential for treating a number of age-related diseases and combating the disability and frailty that accompany the aging process. Developing therapies like these could potentially help older people to enjoy an improved level of physical performance and a better quality of life. Being able to remain mobile and independent as we grow older would be of huge benefit to not only the individual but also to families and society as a whole.

There are currently no FDA-approved treatments for age-related frailty, so this represents a huge unmet need that will only worsen with an increasingly aging population if those needs are not met by new medicines.

Seeing such tangible results in humans is a clear indication of the potential of rejuvenation biotechnology, and how we regard and treat aging will be changing in the near future.

Literature







[1] Nardi, N. B., & da Silva Meirelles, L. (2008). Mesenchymal stem cells: isolation, in vitro expansion and characterization. In Stem cells (pp. 249-282). Springer Berlin Heidelberg.

[2] Stolzing, A., Jones, E., McGonagle, D., & Scutt, A. (2008). Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mechanisms of ageing and development, 129(3), 163-173.

[3] Wang, S., Qu, X., & Zhao, R. C. (2012). Clinical applications of mesenchymal stem cells. Journal of hematology & oncology, 5(1), 19.

[4] Danielyan, L., Beer-Hammer, S., Stolzing, A., Schäfer, R., Siegel, G., Fabian, C., … & Novakovic, A. (2014). Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer’s and Parkinson’s disease. Cell transplantation, 23(1), S123-S139.

[5] Naaldijk, Y., Jaeger, C., Fabian, C., Leovsky, C., Blüher, A., Rudolph, L., … & Stolzing, A. (2017). Effect of systemic transplantation of bone marrow‐derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice. Neuropathology and applied neurobiology, 43(4), 299-314.







[6] Golpanian, S., DiFede, D. L., Khan, A., Schulman, I. H., Landin, A. M., Tompkins, B. A., … & Levis-Dusseau, S. (2017). Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, glx056.

[7] Franceschi, C., Garagnani, P., Vitale, G., Capri, M., & Salvioli, S. (2017). Inflammaging and ‘Garb-aging’. Trends in Endocrinology & Metabolism, 28(3), 199-212.

[8] Tompkins, B. A., DiFede, D. L., Khan, A., Landin, A. M., Schulman, I. H., Pujol, M. V., … & Mushtaq, M. (2017). Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(11), 1513-1522.