How Mass Spectrometry is Accelerating Rare Disease Research

27 Feb 2018

Mimi Roy, Senior Director of Analytical Chemistry, BioMarin Pharmaceutical Inc., explores the impact of mass spectrometry on medical research, right from drug discovery to compound characterization, through drug manufacturing. The superior precision of the latest mass spectrometry technology has enabled the team at BioMarin to accelerate research into rare diseases such phenylketonuria, mucopolysaccharidosis, or haemophilia.

I'm Mimi Roy. I'm Senior Director of Analytical Chemistry at BioMarin Pharmaceuticals. BioMarin has a niche position in the pharma industry. We work only on orphan diseases, diseases that have very small populations that other pharma companies do not particularly want to work on because the market opportunities are seen to be limiting.
Orphan diseases are diseases such as, Phenylketonuria or PKU, MPS or Mucopolysaccharidosis, as well as hemophilia. I've chosen to work in the biopharmaceutical industry because the balance between health and disease has always been fascinating to me.
What is health? When does disease start? And how can we learn about the disease, how it deviates from health? What goes on? And how can we bring people back to health? What I've understood as an analytical chemist is this is all happening at the molecular level and to understand it we need to have very good tools to look at the molecules, look at the disease at the molecular level.
Mass spectrometry has become an extremely useful tool in drug development. We use it in research, in process development, in characterization of the drug before IND filing or BLA filing, as well as in manufacturing to troubleshoot. Mass spectrometry essentially means you're measuring the mass of a molecule and for the mass to get an accurate mass reading, you need the molecule to fly into gas phase and be able to measure its movement in gas phase and infer its mass from its movement.
These days, the resolution and the accuracy is amazing. Our latest instruments can measure to the second, or third, or fourth decimal place the mass of a molecular entity. And what it allows us to do is really use it as an identity for that molecule because nothing else has that particular mass down to that second or third decimal place.
For me, it's been almost as impactful as the internet. The internet allows me to look at the whole world. So does mass spec. In my scientific world it allows me to look at small molecules, peptides, proteins, muscle. There's no limit.
So one transition from the old days to now is that mass spectrometers have become more run of the mill and they've become part of the workflow of an experiment, or a process, or an assay. And the workflow typically involves first having a question of scientific design and then invariably, sample prep leading to analysis with the mass spec, and then a lot of bioinformatics that pulls in software.
The workflow could use robots to make sure that the sample prep is robust and reproducible, and doesn't vary when you change operators. The mass spec itself has become much more robust, much easier to use, and of course, there is software which is an active area of discussion for all mass spectrometrists.
I think if I were to ask other mass spectrometrists in the field, one thing that many people are excited about is multi-attribute monitoring. This is the concept that you can do away with a lot of different release tests by doing a lot of the testing just by using a mass spec. It's an area still being tested, pushed, and pulled, but I'm really excited to see that it's being looked at.
It's very exciting.