Stanford scientists just discovered a new way to make large quantities of a precious drug that holds potential as treatment for cancer, HIV, and Alzheimer’s disease.
Known as bryostatin 1, this compound is currently in high demand for multiple clinical trials. It was originally discovered in the 1960s, in a marine organism commonly known as bryozoan, or scientifically as Bugula neritina. In labs, the compound showed promise against cancer and other diseases. But when researchers went back to the sea to get more bryozoan, they were met with many hurdles.
First, the process of extracting bryostatin 1 from B. neritina is excruciatingly difficult with very low yield. From 14 tons of B. neritina, scientists isolated just 18 grams of the precious bryostatin 1 compound. "It's basically three elephants going down to a salt shaker," said Dr. Paul Wender, a professor of chemistry and member of Stanford ChEM-H, and the study’s lead author.
To make matters worse, the supply B. neritina was also difficult to obtain, as the organism only produces the bryostatin compound in a narrow depth and temperature range.
While scientists toiling away in the lab came up with a synthetic version of bryostatin 1, it took 57 steps for similar low yields.
The demand for bryostatin 1 was simply too high for the supply, which was drying up and preventing clinical trials from going forward.
"Ordinarily, we're in the business of making chemicals that are better than the natural products,” Wender said. "But when we started to realize that clinical trials a lot of people were thinking about were not being done because they didn't have enough material, we decided, 'That's it, we're going to roll up our sleeves and make bryostatin because it is now in demand.”
The efforts of the team proved fruitful, as they came up with a process that’s almost half the number of steps (29 instead of 57), and with a significant increase in yield, as compared to extracting the compound from B. neritina itself.
“The talent and dedication of this group made possible an achievement which many had thought impossible,"Wender said. "We are so fortunate to have people who are undeterred by that."
Using their new protocol, the lab produced over 2 grams of bryostatin 1. While that may not seem like a lot, remember that only 18 grams were extracted from 14 tons of B. neritina. By scaling up production, the team estimates to make 20 grams of bryostatin 1 in a year, an amount which reportedly can treat 20,000 cancer patients.
The drug is also in-demand for clinical trials involving Alzheimer’s patients as well as HIV patients. No doubt the mass production of bryostatin 1 will facilitate discoveries on multiple health areas in the future.
Additional source: Stanford