Hematopoietic stem cells can save lives in the treatment of blood cancer, but hurdles remain to effectively harvest them for transplantation. A research team at the University of California, Santa Cruz has evidence that Pfizer’s popular erectile dysfunction drug Viagra can facilitate the release of stem cells from the bone marrow into the bloodstream, which could ease collection.
Transplantation practitioners traditionally mobilize stem cells using standard granulocyte-colony stimulating factor (G-CSF)—namely, Amgen’s Neupogen (filgrastim). The UC Santa Cruz team found that pairing Viagra with Sanofi’s stem cell mobilizer Mozobil (plerixafor) worked almost as well in mice, the team reported in the journal Stem Cell Reports.
“Given that both drugs are FDA approved, they could be relatively quickly tested in human volunteers,” the study’s senior author, Camilla Forsberg, said in a statement. If successful, it could provide a new strategy for stem cell transplant preparation, she argued.
Even though G-CSF agent works in most donors, it needs to be given for several days before the stem cells can be collected. It’s costly and can cause side effects such as fatigue, nausea and bone pain.
The Forsberg lab previously showed that increasing the ability of blood vessel walls to allow molecules through—known as vascular permeability—could help hematopoietic stem cells escape from bone marrow and into the blood. So Forsberg and her team hypothesized that Viagra, which relaxes blood vessel walls, might promote stem cell mobilization. After all, the drug was originally designed to address cardiovascular diseases and is sometimes used to treat pulmonary hypertension.
In mice, a single oral dose of Viagra and an injection of Mozobil induced about 2,500 more hematopoietic stem cells to enter the bloodstream within just two hours, representing a 7.5-fold increase compared to control mice. In contrast, Viagra alone wasn’t effective, and Mozobil monotherapy only showed about a threefold increase. While three days of Viagra yielded slightly better results, the researchers figured the outcome from just one dose could already rival the performance of Neupogen, which is meant to be given for at least four days.
The researchers went on to transplant the harvested stem cells into other mice. The animals that received cells resulting from the Viagra-Mozobil combo ended up with superior engraftment of functional, multipotent stem cells than did those given cells from mice that received Mobozil alone, the team reported.
RELATED: Eli Lilly's erectile dysfunction drug Cialis shows signs of reversing heart failure in sheep
Often dubbed “the little blue pill,” Viagra has been available in the U.S. to treat erectile dysfunction for about two decades, and scientists are still finding potential new uses for it.
University of Manchester researchers recently found that Eli Lilly’s Cialis (tadalafil), which belongs to the same PDE5 inhibitor class as Viagra, slowed the progression of heart failure in sheep models. In a 2018 study published in OncoImmunology, scientists at Ottawa Hospital Research Institute showed a combination of Viagra or Cialis plus Seqirus’ flu vaccine Agriflu could significantly reduce the chance of cancer spread post-surgery in mice. The PDE5 inhibitors could block myeloid-derived suppressor cells and in turn allow natural killer cells to target metastatic cancer cells, the team found.
In recent developments from the Repurposing Drugs in Oncology project, researchers also identified a wide range of mechanisms of action from PDE5 drugs that could be complementary to other drugs in treating cancers, including the notoriously hard-to-treat glioblastoma.
Forsberg and colleagues now plan to work with clinicians to advance their current findings into human studies. The hope is that Viagra-Mozobil could offer a more affordable alternative to G-CSF. The simplicity of administration and better safety profile “would likely attract more volunteer donors and make [hematopoietic cell transplantation] a reality for additional patient cohorts,” the authors wrote in the study.