What does the future hold for longevity research? Many clinical trials are currently investigating therapies that could lead to increases in human lifespan and healthspan. Here are some clinical trials that we think have the potential to deliver promising results within the next few years. Most of these are expected to conclude in 2021. We also favoured trials in their later phases, as these should be closer to seeing real clinical application.
It has become clear that molecules present in blood plasma play an important role in the ageing process. Injecting old mice with young blood has rejuvenating effects, but work still needs to be done to determine which molecules are responsible and whether they can be used to improve human health.
Alkahest is a company behind a number of clinical trials with the goal of answering that question. The phase 2 trial of GRF6021 (an intravenous injection of young blood factors) aims to study safety and effectiveness for improving cognitive function in Parkinson’s disease. This trial completed in 2020.
Three more phase 2 trials are currently underway for AKST4290. AKST4290 is an oral drug that inhibits eotaxin, a molecule identified by Alkahest that increases with age. These trials are investigating AKST4290’s safety and effectiveness in the treatment of Parkinson’s disease, age-related macular degeneration and pemphigoid (a family of autoimmune conditions that affect the skin and mucous membranes). They are expected to conclude in 2021.
Senolytic compounds are drugs that are designed to remove senescent cells – ‘zombie’ cells that are no longer capable of dividing. Senescent cells release harmful molecules that contribute to most diseases of ageing, so it is hoped that removing these cells could yield substantial benefits for a wide variety of conditions.
This phase 2 trial is one of multiple studies investigating the potential of senolytics for treating age-related diseases, in this case chronic kidney disease. Last year was not a good year for these drugs, as UNITY Biotechnology’s phase 2 senolytics trial failed to show any improvement for patients with knee osteoarthritis. The senolytics used in the Mayo Clinic trial, Dasatinib and Quercetin, might be more promising. These drugs have been shown to clear senescent cells in humans, and very early results suggest they improve physical ability in those with idiopathic pulmonary fibrosis. We are therefore optimistic that this trial, set to conclude in 2021, may yield positive results.
Rexlemestrocel-L is a treatment consisting of mesenchymal precursor cells, a form of stem cell that is capable of specialising to become a variety of cell types including those found in heart and bone tissue. These cells are extracted from the patient’s bone marrow to be replanted, in this case into the spine to treat lower back pain caused by degeneration of the intervertebral discs. The phase 3 trial for rexlemestrocel-L is set to finish in early 2021.
A phase 3 that concluded in 2020 also reported that rexlemestrocel-L could significantly reduce mortality in patients with advanced heart failure, and Mesoblast plans to meet with the FDA to discuss potential approval of rexlemestrocel-L for the treatment of heart failure in the US.
Osteoarthritis is a debilitating disease of ageing and is the most common type of arthritis, affecting over 30 million adults in the U.S. Treatment for osteoarthritis focusses on pain relief, as there are no currently approved treatments that target the underlying disease process (termed ‘disease-modifying drugs’).
Lorecivivint is a drug that acts on a signalling system used by cells called the Wnt pathway. Early evidence suggests that lorecivivint not only reduces inflammation, but can also slow the degradation of cartilage and stimulate the growth of new cartilage. This makes Lorecivivint exciting, as it has the potential to slow or reverse the disease process to some extent, making it a disease-modifying drug. Three phase 3 trials for Lorecivivint are currently underway, two of which (NCT04385303 and NCT03928184) are expected to finish in 2021.
NAD is a molecule that is essential for mitochondria, the power plants of the cell, to produce energy. With age, NAD levels decline as mitochondria become damaged, and this decline in NAD levels is thought to be integral to the ageing process – for a more detailed explanation of why, you can take a look at this article.
Administering precursors of NAD, such as nicotinamide riboside (NR) have the potential to slow or reverse some aspects of ageing by restoring NAD levels in older people. This could impact a very wide range of diseases, which is why this phase 1 trial is on the list despite being in its early stages.
Older people can take much longer to recover from illness and injury than younger people. This trial will assess whether oral NR can speed recovery time and improve outcomes in patients suffering from inflammation or acute illness (illness with a rapid onset and expected return to normal health). It is expected to conclude around the end of 2021.
Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study: DOI: 10.1016/j.ebiom.2018.12.052
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