Forbes
Oct 10, 2019
Victoria Forster
https://www.forbes.com/sites/victoriaforster/2019/10/10/viagra-may-enhance-common-treatment-for-leukemia/#132f229eda5b
One of the most well-known uses for blood stem cell transplants is to treat blood cancers like leukemia, but they are actually used to treat dozens of different conditions. Sometimes, patients donate their own blood stem cells and then are transplanted back in later, for example before having chemotherapy for cancer. Much of the time, however, blood stem cells are donated by other people, either family members of the patient or even complete strangers.
However, donating blood stem cells is not simple. Donors need to be given several doses of a growth factor called G-CSF to stimulate the bone marrow, where blood stem cells are produced and stored, to release them into the circulating blood so they can be easily collected. G-CSF is present normally in the body at certain levels, but this needs to be supplemented with higher levels before blood stem cell donation. Unfortunately, G-CSF causes side effects in many stem cell donors, including nausea, fatigue and bone pain. It often also fails in people who have previously had chemotherapy and those who are elderly or frail.
Now researchers from the University of California in Santa Cruz may have come up with a perhaps, unusual solution to this. Work published today in Stem Cell Reports tested the effect of two FDA-approved drugs; Plerixafor and Viagra on blood stem cell mobilization in mice, with the hope that this can soon be translated to human clinical trials.
Plerixafor is FDA-approved for this purpose in patients with some cancer types, but often not as effective as G-CSF. Viagra is approved for...another indication and works by causing vasodilation, which widens blood vessels. The researchers theorized that using these drugs together would mean that more blood stem cells could move from the bone marrow to the circulating blood, where they can be easily extracted from a donor by a machine. The team found that Plerixafor alone did increase mobilization of blood stem cells, but the addition of Viagra greatly increased the numbers of cells found in the circulation almost to the same levels of mice treated with G-CSF.
These early results have only been seen in mice so far, but the researchers hope that if these results are replicated in human trials, the drug combination could represent another option for blood stem cell donors. Crucially, the mice seemed to experience no side-effects of the Viagra combination treatment, meaning if these results are replicated in human trials, human blood stem cell donors could experience a faster, cheaper procedure with fewer side effects than with the G-CSF used currently.
"It is possible that the drug combination will have side effects in humans, even though each drug alone is safe," said senior author of the paper, Professor Camilla Forsberg, a stem cell biologist at the University of California, Santa Cruz. "Given that both drugs are FDA approved, they could be relatively quickly tested in human volunteers. We do not work with patients ourselves, but we are interested in partnering with physicians to translate these findings to humans," she added.
As well as being a good replacement or addition to the existing G-CSF treatment, it may also be more suitable for people who generally respond poorly to G-CSF, such as elderly people, those who have already undergone chemotherapy or people with certain diseases like sickle cell anemia. In this case, the genetic mutation which causes the red blood cells to be misshapen can be theoretically corrected by genetically altering blood stem cells with techniques such as CRISPR and human clinical trials are ongoing.
But for this to work, enough blood stem cells need to be collected for researchers to edit in the lab. G-CSF is dangerous for these patients as it increases the number of blood cells and exacerbates the problem of their blood cells getting stuck in vessels because of their unusual shape.
"It is actually possible that Viagra will be beneficial for certain patients: one of the potential target groups is kids and adults with sickle cell disease, as they cannot tolerate G-CSF. Viagra, by acting as a vasodilator, may alleviate the symptoms of sickle cell disease which is caused by pain from "sickled" red blood cells obstructing blood flow," said Forsberg.
The mice treated with Viagra alone didn't show any signs of increasing their mobilization of blood stem cells, so people who take Viagra for other reasons need not be worried, but the question everybody reading this is likely to be asking is, well did male mice treated with Viagra experience the "intended" effects of Viagra? Not noticeably, but larger mammals on a human clinical trial may.
"Yes, Viagra is likely to exert its normal effects - we believe that the increase in blood stem cell mobilization is directly linked to vasodilation, which also promotes erections in males," said Forsberg.
So, the first (human) males to test this will likely be warned about this particular possible side effect, but based on the mouse results they can be hopeful that any other side-effects will be limited.
Oct 10, 2019
Victoria Forster
https://www.forbes.com/sites/victoriaforster/2019/10/10/viagra-may-enhance-common-treatment-for-leukemia/#132f229eda5b
One of the most well-known uses for blood stem cell transplants is to treat blood cancers like leukemia, but they are actually used to treat dozens of different conditions. Sometimes, patients donate their own blood stem cells and then are transplanted back in later, for example before having chemotherapy for cancer. Much of the time, however, blood stem cells are donated by other people, either family members of the patient or even complete strangers.
However, donating blood stem cells is not simple. Donors need to be given several doses of a growth factor called G-CSF to stimulate the bone marrow, where blood stem cells are produced and stored, to release them into the circulating blood so they can be easily collected. G-CSF is present normally in the body at certain levels, but this needs to be supplemented with higher levels before blood stem cell donation. Unfortunately, G-CSF causes side effects in many stem cell donors, including nausea, fatigue and bone pain. It often also fails in people who have previously had chemotherapy and those who are elderly or frail.
Now researchers from the University of California in Santa Cruz may have come up with a perhaps, unusual solution to this. Work published today in Stem Cell Reports tested the effect of two FDA-approved drugs; Plerixafor and Viagra on blood stem cell mobilization in mice, with the hope that this can soon be translated to human clinical trials.
Plerixafor is FDA-approved for this purpose in patients with some cancer types, but often not as effective as G-CSF. Viagra is approved for...another indication and works by causing vasodilation, which widens blood vessels. The researchers theorized that using these drugs together would mean that more blood stem cells could move from the bone marrow to the circulating blood, where they can be easily extracted from a donor by a machine. The team found that Plerixafor alone did increase mobilization of blood stem cells, but the addition of Viagra greatly increased the numbers of cells found in the circulation almost to the same levels of mice treated with G-CSF.
These early results have only been seen in mice so far, but the researchers hope that if these results are replicated in human trials, the drug combination could represent another option for blood stem cell donors. Crucially, the mice seemed to experience no side-effects of the Viagra combination treatment, meaning if these results are replicated in human trials, human blood stem cell donors could experience a faster, cheaper procedure with fewer side effects than with the G-CSF used currently.
"It is possible that the drug combination will have side effects in humans, even though each drug alone is safe," said senior author of the paper, Professor Camilla Forsberg, a stem cell biologist at the University of California, Santa Cruz. "Given that both drugs are FDA approved, they could be relatively quickly tested in human volunteers. We do not work with patients ourselves, but we are interested in partnering with physicians to translate these findings to humans," she added.
As well as being a good replacement or addition to the existing G-CSF treatment, it may also be more suitable for people who generally respond poorly to G-CSF, such as elderly people, those who have already undergone chemotherapy or people with certain diseases like sickle cell anemia. In this case, the genetic mutation which causes the red blood cells to be misshapen can be theoretically corrected by genetically altering blood stem cells with techniques such as CRISPR and human clinical trials are ongoing.
But for this to work, enough blood stem cells need to be collected for researchers to edit in the lab. G-CSF is dangerous for these patients as it increases the number of blood cells and exacerbates the problem of their blood cells getting stuck in vessels because of their unusual shape.
"It is actually possible that Viagra will be beneficial for certain patients: one of the potential target groups is kids and adults with sickle cell disease, as they cannot tolerate G-CSF. Viagra, by acting as a vasodilator, may alleviate the symptoms of sickle cell disease which is caused by pain from "sickled" red blood cells obstructing blood flow," said Forsberg.
The mice treated with Viagra alone didn't show any signs of increasing their mobilization of blood stem cells, so people who take Viagra for other reasons need not be worried, but the question everybody reading this is likely to be asking is, well did male mice treated with Viagra experience the "intended" effects of Viagra? Not noticeably, but larger mammals on a human clinical trial may.
"Yes, Viagra is likely to exert its normal effects - we believe that the increase in blood stem cell mobilization is directly linked to vasodilation, which also promotes erections in males," said Forsberg.
So, the first (human) males to test this will likely be warned about this particular possible side effect, but based on the mouse results they can be hopeful that any other side-effects will be limited.