Fight Aging!

It is time once again for my once-yearly set of unsolicited thoughts on biotech startups that I'd like to see join those already working hard on the basis for human rejuvenation. The industry is growing rapidly, but patchily. Partial reprogramming has received enormous attention, as has the development of senolytics. Meanwhile, other important goals in rejuvenation research languish, or presently have only one or two companies involved in clinical translation of promising academic projects. Many plausible paths forward go undeveloped; there are just as many opportunities to make a real difference in the world as there were a decade ago.

Cell Therapy for Thymus Regrowth

The thymus atrophies with age, reducing the production of new T cells to a fraction of what it once was. The adaptive immune system declines as a result, becoming cluttered with dysfunctional, broken, and worn cells. One of the more promising approaches to regrowing the aged, atrophied thymus involves intravenous delivery of cells, either progenitor thymocytes or endothelial cells, that home to the thymus. Once there, they promote growth of active thymic tissue. This has been demonstrated in mice, but the groups involved have moved on to try to find small molecule approaches, so far with only very limited progress to show for it. So why not take this cell therapy approach and bring it to the clinic? Production of universal cells from lines engineered to avoid immune rejection is presently a going concern. This is a good time to be innovating in the cell therapy sphere.

Bring Fecal Microbiota Transplantation into Widespread Use

One particular implementation of fecal microbiota transplantation was recently approved by the FDA for use in the treatment of C. difficile infection. Beyond this formal arena of medicine, there is a thriving community of individuals attempting to treat their own dysbiosis, and informal clearing houses that attempt to characterize and screen donor samples for safer use. It is well demonstrated in animal models that fecal microbiota transplantation from young to old produces a lasting rejuvenation of the gut microbiome, improved health, reduced inflammation, and extended life span. The timing has never been better to establish a venture that demonstrates the merits of this approach in humans, and then does its best to make fecal microbiota transplants available to the millions of older people who could benefit.

A Better Approach to Reversing Tissue Calcification

The state of the art in reversal of the calcium deposition and consequence loss of elasticity in the aged cardiovascular system and elsewhere is typified by Elastrin's technology, which is to say a focus on ways to improve on the established mode of EDTA chelation therapy by using a far more targeted delivery system. Is there a better way forward that can lead to larger effect sizes, a greater reduction in calcification? One would think that there should be, indeed must be if this aspect of aging is to be fully reversed.

Solutions to the Systemic Delivery Issues of Gene Therapy

Presently available gene therapy delivery techniques struggle to achieve a number of important goals. Delivery to the liver may be more or less a solved problem, but many other problems remain unsolved. Sufficient delivery throughout the body without excessive delivery to the lungs or liver following intravenous injection, for example. Or delivery to a specific minor internal organ, with minimal delivery elsewhere, following intravenous injection. Delivery platforms that can provide relatively off the shelf, 80/20 solutions to delivery of gene therapy payloads in these and other important circumstances have yet to be brought into being, but are very much needed.

A Way to Inhibit Alternative Lengthening of Telomeres

Targeting telomerase and telomeres in the clinical treatment of cancer has started in earnest with Maia Biotechnology. It remains the case that something like ~10% of cancers use alternative lengthening of telomeres (ALT) rather than telomerase to bypass limits on cell replication, however, and there is as of yet no good approach to inhibition of ALT. One of the reasons why ALT is an attractive target is that it does not operate in normal, non-cancerous cells, which removes many of the normal issues regarding off-target effects in the inhibition of cellular mechanisms. There is room here for a group to perform a broad screen for ALT inhibitor small molecules, in search of a useful lead for a preclinical development program.

Safely Replace the Hematopoietic System

The generation of immune cells occurs in the bone marrow, the responsibility of hematopoietic stem cells and descendant progenitor cell populations. While the mechanisms of aging, particularly chronic inflammation, are disruptive of the niche structures that support hematopoietic cells, there is also damage to the cells themselves. It has long been possible to replace hematopoietic cells, but this is a procedure that requires aggressive chemotherapy to clear existing populations, and comes with a non-trivial degree of risk. To introduce a new population of engineered hematopoietic stem cells into most old people, an entirely new, safer, and more gentle strategy will be needed. Consider the production of universal or patient-matched hematopoietic stem cells that are changed in ways that allows them to outcompete native cells and take over stem cell pools in the bone marrow, for example.