The Dana-Farber/Baylor collaboration started when Bradner told Matzuk that he was testing JQ1 as an inhibitor of a member of a family of bromodomain proteins, and he wanted to know whether JQ1 would have an effect on a spermatogenic-specific member of that family called BRDT. This question was based on earlier research from Debra Wolgemuth, PhD, and her group at Columbia University that revealed that mice lacking BRDT were infertile.
BRDT is involved in the chromatin remodeling process during the generation of sperm in the testis. Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. It is "remodeled" to give the proteins that regulate how genes act access to the genetic material.
JQ1 subverts that process by binding to a pocket of BRDT that is necessary for chromatin remodeling to take place. In doing this, JQ1 blocks the normal process by which sperm are made, thereby reducing production and quality of the sperm.
Using JQ1 provided by Bradner, Matzuk and his group injected mice with the compound in solution and evaluated the effect. The mice that received JQ1 had lower sperm counts, and their sperm were less mobile than those of mice who had not received the molecule. This rendered the JQ1-treated mice infertile.
"These findings suggest that a reversible, oral male contraceptive may be possible," said Bradner, who is also on faculty at Harvard Medical School and the Broad Institute. "While we will be conducting more research to see if we can build on our current findings, JQ1 shows initial promise as a lead compound for male contraception."
Dr. James Bradner talks about how he and other researchers at Dana-Farber Cancer Institute and Baylor College of Medicine used a small molecule compound to generate reversible birth control in male mice
(Photo Credit: Dana-Farber Cancer Institute)
Researchers at Dana-Farber Cancer Institute have used a small molecule compound to generate reversible birth control in male mice.
(Photo Credit: Dana-Farber Cancer Institute)
Source: Dana-Farber Cancer Institute