The Champion of N=1 Studies

Roxana Redis and her Charles River team fight for rare disease patients

Dr. Roxana Redis, PhD, is the Science Director of Advanced Modalities at Charles River’s Leiden, Netherlands site. Her team is responsible for handling our scientific capabilities in gene therapy drug discovery, specifically in antisense oligonucleotides (ASOs). But according to her manager Stefan Kostense, Director of Biology, it goes far beyond the typical communication with clients.

“Our department is specialized in drug discovery using complex biology,” Kostense said. “Roxana is our champion in so called N=1 studies, or studies dealing with one patient suffering a rare disease for whom we are trying to find a drug. Quite often, the parents themselves are the clients with whom we have direct interaction about the progress of the study. Therefore, we are well aware of the impact of every success, or every set back on the parents who are trying to help their child.”

N=1 patients are a rare subset of an already rare subset of patients who suffer from an orphan disease – or a disease with no known treatment. These patients typically have an extremely rare genetic mutation that is causing them harm, and researchers who are trying to help them have the double task of learning everything they can about an unknown disease while simultaneously trying to find a treatment. 

Redis has worked for Charles River for six years, coming on board right before the pandemic that would shift experimental therapies to the mainstream.

“[The pandemic] pushed mRNA to what it is today, and that for me was a very exciting breakthrough,” she said. “Not only showing the potential that mRNA has, but also kind of the potential that we as society have when we channel our efforts towards something. The breakthroughs that we can achieve are, to me, remarkable.”

Redis says she was always interested in science and began her academic career in chemical engineering. She moved on to a PhD in medicine and genetics, writing several papers on non-coding RNAs and their involvement in cancer biology. She began her PhD in Romania, but earned a scholarship to study abroad and landed in Texas at the MD Anderson Cancer Center. A ten-month internship turned into five years, where she finished her PhD and a two-year postdoc.

“I've worked in the RNA space my entire career and everything that is related to RNA has always fascinated me,” she said. “Actually my entire career I've been working at the beginning of a drug development process.”

The hidden trap of academia can be falling in love with a hypothesis, running it down to the ground and losing sight of a bigger picture. On Redis’ team, the goal is real world results, and the motivator is a living patient who needs a therapy yesterday. If a hypothesis is shaky, it is discarded quickly. No idea is more precious than the ultimate goal: finding a treatment for an orphan disease.

“[Academia] felt too far away from the patient, and one of the things that I love about my job right now is the fact that I work with these families and these foundations directly. So I see the people that I work for and who my work is going to help.”

What makes her job rewarding, can also make it emotionally taxing. Seeing the patients and their families and dealing with them directly, constantly giving them updates that are both good and bad, can take a toll on a researcher. For Redis, this motivation can be personal.

“Every story and every family is special. I have a four-year-old son, and whenever we work with a child that is close to my son’s age, I think ‘this could have been my child.’ I find that in a way motivating because I think, OK, I want to help these people and I'm going to put all my effort into it because if I were in their shoes, I would want someone to help me as well.”

Researching real patients is rarely a linear process. In many cases they have to start from scratch, investigating the disease alongside potential treatments. Redis is proud that her team can work independently, with each member bringing a unique perspective to the work while she streamlines the process and keeps the families updated.

“There's one program in particular that we've been working for a year, and still every day we get some new piece of data that makes it exciting but also challenging,” she said. “It really needs a lot of work and even more out-of-the-box thinking.”

Her first job after academia was in The Netherlands, at a small biotech company developing RNA editing technology. Now this is a well-known research area, but in 2016 it was more theoretical. She was part of a team to take the academic exercise from theory to therapeutic, much like she now does every day at Charles River. She says her team feels like a small academic lab within the larger organization of Charles River, since they are always working on complex biological questions which are not perfectly understood.

The one thing Roxana thinks could help patients the most is better dialogue with regulatory agencies. She believes that offering more customizable programs to accommodate the N=1 patient framework could make a big difference and could make the research more appealing commercially to investors.

“Collaboration is key between academia, CROs, and industry,” she said. “It’s a small world, just a few patients, so if we learn from each other, we can help more and push this field forward faster.”