Wyss Institute to Investigate Sex Disparities With FDA-funded Chip Technology Study
Under a newly expanded research contract with the US Food and Drug Administration (FDA), Harvard University’s Wyss Institute will use its organ-on-chip technology to investigate how bone marrow responds to radiation and certain drugs differ between men and women.Wyss’ FDA-funded investigative studies involving chip technology date back to 2013 when the agency first awarded the institute a contract valued at more than $5 million to develop a bone marrow chip, a gut chip and a lung chip that can recapitulate function outside of a human body to then evaluate the effects and develop countermeasure drugs for treating radiation-type injuries.
The bone marrow chip is one the institute’s “newer chips” and it is “very exciting,” Wyss senior staff scientist Rachelle Prantil-Braun told Focus. The new follow-on study with the investigative bone marrow chip expands on the 2013 FDA contract with $398,000 in new funding granted in September after the results attracted the attention of the agency’s Office of Women’s Health.
Prantil-Braun, who is also a research lead in the FDA project, noted that the study results have already showed the bone marrow chip is capable of producing human red and white blood cells, maintaining a CD34 cell population as well as mimicking the marrow’s responses to acute radiation exposure, a chemotherapeutic drug (5-FU) and radiation countermeasure drugs.
Wyss researchers encountered a problem with how males and females respond to drugs differently during its mission to develop better models for drug discovery and new countermeasure drugs via its organ on chip program. There were also “a lot of questions about sex-specific differences” in discussions with FDA’s Office of Women’s Health, Prantil-Braun noted. The Wyss researchers realized during the process of putting together its grant application that all its donors were male, despite being from various different sources, she added.
Sex disparities have come under the spotlight recently with the a number of new initiatives underway at FDA’s Office of Women’s Health. Chips also present unique regulatory challenges as one of many emerging technologies the FDA and industry are grappling with to better understand.
The new follow-on study is intended to bridge the research gap between female vs. male bone marrow responses coupled with further understanding the potential of the Wyss bone marrow chip. The question posed by Prantil-Braun and her team to guide the research project is whether the bone marrow chip can be used for human experimentation in vitro—meaning outside the body—to actually recapitulate more predictive measures of drugs for patient treatment.
Wyss’ study also speaks to FDA’s renewed push to further support medical countermeasure (MCM) development, with $170 million in 2010 funding from the US Department of Health and Human Services for an initiative across the Center for Biologics Evaluation and Research, the Center for Drug Evaluation and Research and the Center for Devices and Radiological Health.
The MCM initiative is also funding the new follow-on study because the animal models that drug sponsors have typically used to file an investigational new drug (IND) application with FDA have had a low success rate, according to Prantil-Braun. “Of all drugs that start from the beginning of the drug discovery process, only 11% of them are successful when they make it to the clinic.”
Microbiotechnology that mimics human organ function has the potential to replace animal testing and help bring new therapies to more patients at a faster pace and at a lower cost.
FDA officials want to be involved in the Wyss’ processes around its organ on chip technology program “so that they understand how to direct it, how to move it forward and how to implement it into filing INDs for drugs,” Prantil-Braun said. “Human is better, but you also need to make sure that the actual human organ on chips replicates certain types of functions that are necessary not just for efficacy but also toxicity, which is really the biggest problem,” she added.
Another challenge facing the Wyss research team under the organ on chip technology program relates to capturing what may happen with implanted patients in the clinic by showing the its human models have human function outside of the body similar to what happens in vivo. This is also part of the reason FDA is funding the research, according to Prantil-Braun. “We work heavily with industry to make sure that we actually are showing what they see in the clinic.”