“Translational research” is a popular term these days, with special relevance for the fields of science and technology. While the process of translational research and commercialization remains complex with many players involved, the overall message is clear: it is the translation of basic research in a lab to a tangible treatment or symptom management tool that is accessible to the person who needs it. Translational research is that step, or many steps, that needs to happen so that discoveries in science can have a real-life benefit for people living with MS.
Today, the MS Society announced funding for two innovative translational research projects focused on progressive MS, in collaboration with the Centre for Drug Research and Development (CDRD). Based in Vancouver, BC, CDRD specializes in helping researchers translate their findings into tangible clinical outcomes. A key element of these recently funded projects is a focus on accelerating the development of new therapeutics for people living with progressive forms of MS. With the help of CDRD, these researchers will explore novel drug targets that, if further developed, have the potential to slow, stop, or reverse progression. We know this is an area of MS research that is urgent, and our collaboration with CDRD aims to speed up the process!
This is where translational research comes in. Translational research works by taking scientific discoveries from “bench to bedside”. This process is not always straightforward, and requires coordination between different players in the drug development and regulatory arena. For translational research to work, there needs to be a great deal of communication between all players to accelerate the pace of research and ensure that a treatment is approved for use and made available to people who need it.
From bench to bedside: A three-step process
Before you can wrap your head around translational research, it’s important to understand the steps involved in pushing an idea through the development pipeline with the intention of creating an approved therapeutic that will improve quality of life for people living with MS.
Step 1: Discovery
In the discovery – or basic science – phase, researchers focus their attention on a cultivating new information about a disease. For the purposes of developing treatments, basic science helps researchers identify new targets, such as a protein or gene, which they believe may be contributing to the development of the disease. For MS, potential drug targets may be proteins that impact myelin repair or the activity of immune cells.
Researchers at academic institutions excel at uncovering new information about MS and target identification. However, the avenues through which they can apply this information to create new treatments are less defined, and as a result many new discoveries remain in the lab. This ultimately creates a gap that is often difficult to fill without the adequate funding, resources and expertise needed to help move new drugs through the development pipeline.
Step 2: Translational research
Imagine you’re a manager for a company who’s looking to hire a new employee in your division, and a few dozen applications come in for the position. Your task is to screen the line-up of candidates based on a series of qualifications, gradually narrowing down the list to a few top candidates. Your next step is to interview those highest-ranking candidates and whittle down the list further until you’re left with one.
Discovering new treatments works in a similar way. Once the target for a potential therapy is identified in the discovery phase, the next step, called lead identification, is to identify a compound that will interact with the target in some way. This is done using something called a high throughput screen and, much like the screening process for a job interview, it allows researchers to rapidly test massive libraries of compounds and narrow them down to the most suitable candidates.
Next up is the process of lead optimization. Think of this as the job interview stage, or a fine tuning of the list to the best candidates. Lead optimization is the process of finding compounds that are similar to the lead you’ve identified, but are even better candidates because they interact with the target even better, or are less likely to interact with other cells or proteins in the body—which is important for decreasing side effects of treatments.
At this stage of preclinical testing, researchers also measure the activity of the compound in animals to answer the following questions: How quickly is it absorbed? How is it distributed to different tissues? How is it metabolized and excreted? At what dose is the drug toxic? These are all crucial questions researchers must answer to ensure that their compound will be both effective and safe in humans.
Step 3: Clinical trials
This phase represents the culmination of discovery and translational research efforts, which lead to the testing of potential treatments in humans to determine whether they are safe and effective. You can read more about clinical trials on the MS Society’s website and in one of my past research decoders.
Key players in translational research
CDRD is a fully-integrated centre that combines teams of scientists and commercialization experts with specialized infrastructure and facilities that are ideally suited to carrying out translational research. By collaborating with CDRD, the MS Society is providing both funding and resources for MS researchers who have identified a disease target through their discovery research and want to bring it into the development pipeline.
Two outstanding projects were selected by a rigorous review process to move forward with key translational steps in collaboration with CDRD. The project by Dr. David Granville – which investigates molecules that inhibit the Granzyme B target involved in nerve cell damage – takes advantage of CDRD’s experimental model platform for testing how lead compounds are absorbed, distributed, metabolized and excreted in the body. On the other hand, Dr. Veronique Miron’s project will use CDRD’s comprehensive library of different compounds to perform a library screen and test potential compounds against a target she’s identified that is involved in repairing myelin. Both Drs. Miron and Granville now have access to highly specialized expertise and equipment to undertake this work while gaining important experience in drug development.
The MS Society has also forged a collaboration with Fast Forward, a non-profit subsidiary of the U.S. National Multiple Sclerosis Society (NMSS) that boasts an extensive partnership network with academic institutions and the biotechnology and pharmaceutical communities. Early last year, Fast Forward put out a call for research applications focused on translating research findings into potential myelin repair treatments. A group of researchers at New York University led by Dr. James Salzer were co-funded by Fast Forward and the MS Society to pursue development of a compound that can stimulate the body’s own stem cells residing in the brain to repair myelin.
Translational research and commercialization will be a hot topic for us in the coming year, so keep an eye out for more posts on the subject. As the MS Society continues to fund a wide variety of research to discover the cause and a cure for MS, translational research is a path the Society is pursuing in order to improve quality of life for people living with MS as quickly and efficiently as possible.