In our previous blog, we took a walk through the early stages of the research journey, learning how researchers discover new things about MND and how they prove that these discoveries are ‘true’. Next, we will continue with our research journey, finding out what happens after a result in proven to be ‘true’ in the lab.
Stage 4: Is a result that’s ‘true’ in the lab also true in people?
At this stage, many hours have been spent in the lab, doing experiments and proving that the results are ‘true’ and consistent. The research is ready to be taken out of the lab, to people with MND. Even if a result is found to be consistently true in the lab, in all the different models tested, this doesn’t necessarily mean it will be true for every person living with MND.
Even though we can prove that something specific is happening in MND models and can prove that a treatment fixes this problem in the lab, we don’t know how the treatment will work in the context of a whole human body. A treatment which shows promise in the lab may cause side effects we don’t know about, or the treatment might do something else in the body that we haven’t realised, or it might not be able to reach the brain. It may even be that the treatment is successful in fixing the faulty process, but that it doesn’t influence MND progression or symptoms in people.
This is why clinical trials are so important. They give the chance for treatments which have shown promise in the lab to be carefully tested in people to prove that they are safe and work effectively. Unfortunately, some clinical trials are unsuccessful, likely because of the challenges we have described above. It can be incredibly frustrating when clinical trials fail, both for people affected by MND and the researchers who are invested in the science, but many things can still be learned from these trials. For example, if a drug is successful in fixing a faulty process but has no effect on MND symptoms or progression, this shows us that this process is not a key feature in MND and so will push scientists into researching other processes which they may not have previously considered. In some clinical trials, other uses for drugs can be found by accident. For example, the antidepressant medication Trazadone was originally developed for high blood pressure, but during clinical trials, researchers noticed it had more of an effect on mood and sleep. This led to it being repurposed as an antidepressant.
Another challenge researchers face is that there is so much diversity in the way that MND presents in different people. What is ‘true’ for one person with MND may not be ‘true’ for another person with MND. While a treatment might work for one person, it might not work for another person. In the past, it is possible that treatments have failed in clinical trials because they weren’t tested on the right people.
So what can be done about this?
One way this challenge is being addressed is by separating people with MND into different categories. These categories can be based on genetics, symptoms or using biomarkers. Biomarkers are a way to assess what is happening biologically in a person with MND. Categorising people in this way means that researchers can identify who is more likely to benefit from a certain treatment based on their biology, increasing the chances of success in clinical trials. This type of personalised approach to treating MND has already proved to be effective – targeting a specific genetic change has led to success in the case of tofersen.
Bumps in the road: Finding the positives in negative lab data
Of course, the research journey through the lab and out into the clinic is not guaranteed to be a success. There is no way to get around the fact that sometimes experiments don’t give the results you expect, theories get proven wrong and treatments which showed lots of promise in the lab end up not being effective. In science, this is sometimes called ‘negative data’.
MND researchers ask questions and look for answers, but the answers aren’t always what we hope to see. It’s hard to get away from the fact that a lot of time and money is spent on MND research avenues which don’t work out. A negative result is frustrating for everyone, especially when we are all working so hard to find treatments for MND. But the thing is, you never know until you try! When a theory is built on solid, scientific evidence, testing the theory is the only way to know if the theory is true. Testing theories is the basic principle of scientific research. The key word here is testing, not proving, and unfortunately theories are sometimes found to be wrong.
Importantly, that doesn’t mean that this information is useless. Knowing what doesn’t work is just as important as knowing what does work. Closing one door can open several new doors, and disproving one theory can push scientists to develop new, better theories. It’s all part of the research journey!
One of the key factors in MND research is understanding the disease better. For every disproved theory in the lab or in a trial, we are one step closer to understanding the biology of MND. We learn and understand just as much about MND through failure as we do through success. This is why it is important for scientists to share their negative findings with each other, so everyone can learn, and no one repeats the same research. While negative results are frustrating, they are also a natural and useful part of scientific research, which we can learn a lot from.
Looking to the future in the MND research journey
There is a lot to be optimistic about in the world of MND research, despite the bumps in the road. The success of tofersen has shown that MND is treatable, we understand more than we ever have about the biology behind MND, and every day, many researchers work tirelessly to drive forward progress even further. MND researchers share our goal of a world free from MND, and each one has an important part to play in expanding our knowledge and ability to treat the disease.
If you’re interested in going behind the bench and learning more about life in the lab, look out for future blogs in the series!
