Highlights

  • Dr. Scieszka’s vaccine consists of virus-like particles that present protein markers which also exist on the surface of blood vessel senescent cells.
  • The immune system reacts to and mounts a response against the protein markers to subsequently target senescent cells in blood vessels and possibly throughout the body.
  • Injecting mice with the vaccine prolonged their lifespans and rejuvenated organs like the heart and lungs, all the while preventing age-related hair loss.

Dr. David Scieszka, owner of the startup company Vertical Longevity Pharmaceuticals, has high hopes for a potential tissue-rejuvenating vaccine that he helped develop. Presented in an episode of the Optispan podcast with the University of Washington’s Dr. Matt Kaeberlein, Dr. Scieszka discusses how the vaccine works, some promising results from using it in mice, and possible hurdles in applying it to humans.

A Senolytic Vaccine

Dr. Scieszka begins his explanation of the vaccine that works to eliminate senescent cells, saying that it allows the immune system to target a protein marker on these cells called GPNMB. Therapeutics that kill senescent cells are known as senolytics. Hence, this vaccine is classified as a senolytic vaccine. Moreover, cellular senescence is a hallmark of aging, and some researchers have proposed using senolytics against these cells to counteract aging.

Essentially, a fragment of the GPNMB protein is adhered to the surface of the virus-like particle. When the immune system recognizes the particle, it mounts a response to the GPNMB protein. This protein is present on senescent cells within the vasculature, allowing for senolytic action. In this way, the vaccine trains the immune system to target the protein present on senescent cells. Moreover, by mounting a response against this protein target, the immune system can eliminate senescent cells.

What’s more, after injecting mice with the vaccine in a three-dose series, Dr. Scieszka and colleagues found that the vaccine prolonged lifespan. The research team measured cardiopulmonary outcomes while visually classifying hair loss and pelvic organ displacement (known as prolapse). Throughout the study, every organ system they monitored saw a therapeutic benefit.

Applying the Vaccine to Humans

Moving forward, Scieszka and colleagues would like to find whether the vaccine works in humans. To do so, Dr. Scieszka says he is trying to build a board of advisors so that he can perform safety studies, which are necessary before conducting full-scale human trials. If the vaccine does succeed in the safety trials, Dr. Scieszka hinted that he may try to include a few other senescent cell protein markers in the vaccine to increase its efficacy.

While the FDA debates whether aging is a clinical indication, Dr. Scieszka aims to target atherosclerosis — an inflammation-related disease where blood vessels develop abnormalities called lesions. In that regard, he believes his senolytic vaccine may be a cure for this disease, which can be damaging and life threatening if left untreated, making it the #1 killer of Americans.

“This could be the first true cure for atherosclerosis,” says Dr. Scieszka.

It is also possible that the vaccine may work against other age-related conditions besides atherosclerosis, such as dementia. In that sense, Dr. Scieszka says that his senolytic vaccine targets blood vessel senescent cells that directly interface with the circulation. For this reason, any tissues that come into contact with blood, which include all tissues except for the cornea of the eye, may reap some sort of rejuvenation from the vaccine’s senescent cell elimination.

Potential Challenges with Vaccinating Humans

As for potential challenges with applying the vaccine to humans, mounting an immune response against the senescent cell marker, GPNMB, may have off-target effects. Along these lines, GPNMB is important in bone remodeling, making the vaccine unavailable to those under age 25 when the bones are finishing forming.

Moreover, other tissues with this marker that are in a healthy state may undergo adverse effects from the vaccine, which is why pinpointing what cell types express GPNMB is so important. Broadly, it is known that GPNMB upregulation occurs with age. This upregulation is most evident in aortic, lung, white adipose (fat tissue), and in bone marrow senescent cells. Based on the preclinical data, a reduction in senescent fat cells recovered insulin sensitivity; removal of aortic senescent cells cleared aortic plaques; and clearance of lung senescent cells protected against age-related declines. As of yet, it is unclear whether the removal of senescent bone marrow cells will yield therapeutic benefit, but the trends are clear.

Moreover, the group has set their sights on a non-human primate trial. This is a critical prerequisite before human trial feasibility is assessed. Careful planning is always necessary to ensure no adverse effects arise from the vaccine as well as its efficacy.