Stem cell treatment for aging and debilitating disease clinical IND Japan approved
2020-06-11
On June 1, Longeveron announced that its clinical trial application (Clinical Trial Notification, CTN) has been approved by the Japanese Medicines and Medical Devices Agency (PMDA). They plan to start a phase II clinical trial to evaluate the safety and effectiveness of mesenchymal stem cells in the treatment of aging and debilitating diseases [1].
This will open an important milestone in the Longeveron Aging and Degeneration Program, which also includes two Phase II clinical trials being conducted in the United States.
Aging is a common, but reversible, life-threatening geriatric disease that affects millions of Japanese people over the age of 65. Similar ages and aging fragile patients have similar comorbidities and demographic characteristics, but aging and debilitating patients are more susceptible to disease, such as COVID-19.
The clinical features of aging frailty are muscle atrophy, decreased strength, reduced walking (muscle loss), decreased activity and energy levels, poor endurance, nutritional deficiencies, weight loss, and fatigue. In general, these clinical symptoms will lead to a comprehensive decline in body function and increase the risk of disability, personal inability, and death.
"The biological characteristics of aging and debilitating diseases are very complex, including reduced stem cell activity, reduced ability to repair and regenerate tissues, immune aging, and chronic systemic inflammation." Dr. Anthony Oliva is a senior scientist at Longeveron. "Mesenchymal stem cells have multiple mechanisms of differentiation, immunosuppression, and other mechanisms of action. They have the potential to solve these problems and are very attractive candidates for the treatment of aging and debilitating diseases."
According to reports, this institution plans to conduct a randomized, double-blind, placebo-controlled clinical trial in Japan, which will be conducted at the Tokyo National Medical Center for Gerontology and Gerontology (NCGG) at Suruga University Hospital in Nagoya Whether transplantation of donor-derived mesenchymal stem cells can improve the health status of mild to moderate aging and debilitating patients, thereby improving body function, reducing the risk of disability from aging and degeneration, and relying on others' care.
Dr. Hidenori Arai, chairman of the National Center for Geriatrics and Geriatrics in Japan, said, "Japan is one of the most aging and fastest-growing societies in the world, with 30% of Japanese citizens over the age of 65. Prevention and reversal and aging degeneration Related functional decline is one of the country’s top priorities, and regenerative medicine is an exciting and innovative potential treatment option."
More than 200 aging and debilitating patients in the world participate in clinical
At present, the company has built a comprehensive research program on aging and degeneration, and initiated the world's most extensive and advanced clinical research project on aging and degeneration. There are more than 200 patients worldwide receiving mesenchymal dry report treatment . At the same time, Longeveron is carrying out two clinical projects in the United States to explore mesenchymal stem cells for the treatment of aging and degeneration, as follows:
[Phase II multi-center randomized double-blind placebo-controlled trial, planning to recruit a total of 150 subjects, receiving a single intravenous infusion of 2.5*107, 5*107, 10*107, 20*107 LMSCs or placebo to evaluate mesenchyme Effects of stem cell therapy on exercise endurance and exercise duration.
In a phase I/II multicenter randomized double-blind placebo-controlled trial, a total of 22 subjects were enrolled in the open phase I, and 40 subjects have been recruited in phase II. Phase II aims to evaluate whether LMSC transplantation therapy can improve the immune response of the target population, and the weakness is related to the dysfunction of the immune system leading to poor response to influenza vaccines and increased incidence of influenza. 】
Preclinical studies have shown that mesenchymal stem cells can promote cell repair and tissue regeneration through features such as multi-directional differentiation potential, immunomodulatory function, anti-inflammatory, homing properties, and stimulation of endogenous tissue stem cells, thereby treating aging and debilitating diseases. Moreover, several clinical studies have proved the safety and effectiveness of mesenchymal stem cell transplantation.
In collaboration with Longeveron, the Biomedical Research Center of the University of Miami Miller College of Medicine conducted a phase I clinical trial of allogeneic mesenchymal stem cell transplantation for the treatment of aging and debilitating diseases [2]. A total of 15 people were recruited in the trial, and transplantation treatments with different doses of 2*10^7, 10*10^7, and 20*10^7 were received. There were no serious adverse events caused by treatment within 1 month after transplantation, and no obvious donor-specific immune response in the first 6 months. In all treatment groups, the 6-minute walking distance index increased significantly at 3 and 6 months, and TNF-α levels decreased significantly at 6 months. After comprehensively considering all the detection indexes, the 10*10^7 group showed the best treatment effect, and significantly improved the quality of life of the patients.
In the same year, the Miami team published a report on the results of a phase II randomized double-blind clinical trial [3]. The clinical trial enrolled 30 aging and debilitating subjects and received 10*10^7 or 20*10^7 doses of mesenchymal stem cell transplantation or placebo. No adverse reactions related to treatment occurred within 1 month of transplantation. The physical condition and immune function of the 10*10^7 group were improved. The 6-minute walking test, short-term physical fitness test and forced expiratory volume in 1 second were significantly improved. The quality of life of women was improved and the serum TNF level was reduced; 20*10^ The immune function and TNF level in B cells of 7 groups were improved. Mesenchymal stem cell treatment can significantly reduce early and late activated T cells and improve symptoms.
Outlook
China is also facing an increasingly serious aging social transformation. It is of great significance and urgent need to prevent and treat aging-related diseases. The approval of the clinical project of mesenchymal stem cell transplantation for the treatment of aging and debilitating diseases in Japan may give us a positive signal that mesenchymal stem cells may become a new type of cell medicine for the treatment of aging-related diseases and improve the quality of life of the elderly.
