Unlocking the mysteries of the brain

September 09, 2021

Of all the organs in the body, none holds more secrets than the brain. It is at once the most important organ we have, a command center for the entire body weighing just 3 pounds, yet it’s also a black box of mystery that has captivated and confounded generations of scientists. 

“There’s been an exponential gain in our understanding of the brain itself, but we have also been learning about the diseases, through human genetics, human stem cells, animal models and improved imaging,” says Chris Henderson, Ph.D., head of Research at Biogen. As a neuroscientist, Chris points to his area of expertise, amyotrophic lateral sclerosis (ALS), as an example.

Chris Henderson, Ph.D.
Senior Vice President and head of Research at Biogen

“It’s always been recognized as a huge clinical challenge, a dreadful disease and a tough one to take on in developing treatments,” he says. Scientists have been working on ALS for decades, “but it’s only in the last five to 10 years that we’ve really been able to understand what some of the triggers are and what’s actually going on in the brain.”

“Simply understanding those mechanisms opens up a whole world of possibilities in exploring development of possible treatments that could do more than simply make patients comfortable as they wait for an inevitable decline,” explains Kate Dawson, M.D., head of Biogen’s Therapeutics Development Unit.

Kate Dawson, M.D.
Senior Vice President and head of Biogen’s Therapeutics Development Unit

“When I was training in neurology, we did not have any therapies for ALS and we focused on improving quality of life,” she says, “now there are two, and although those treatments help maintain function and can improve quality of life for people with ALS, significant unmet needs remain. As much as it’s a privilege to be able to positively affect the lives of patients and families, I’d much rather be part of an organization working on doing something more meaningful to affecting the disease itself and that is our goal at Biogen.”

Neurological diseases intrude into every aspect of a person’s life. Memory and cognition can deteriorate, but so can a person’s ability to control their movements, or to move at all. Different conditions in the brain can interfere with a person’s ability to speak or even communicate.

Such complexity is intimidating, but also fascinating to scientists. Neuroscience often attracts the most curious, driven minds to solve its problems, but those same minds can find it discouraging in the quest to turn discoveries into effective treatments for Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, traumatic brain injury and similarly devastating conditions. However, that’s not the case at Biogen.

“As a company, we are filled with people who are tremendously passionate about neurological diseases and research,” Kate says. “We see the huge unmet need. I don’t want another neurologist to not be able to offer a patient a potential treatment for these devastating diseases.”

For Biogen, that commitment translates to investment in pursuing research for some of humanity’s most enigmatic diseases. The very challenges that make the brain such a difficult nut to crack also highlight why medical advances in brain science matter so much as scientists begin to overcome some of the obstacles that previously blocked progress in drug discovery.

One such obstacle is literally a barrier: the blood-brain barrier, a physical boundary surrounding the brain’s blood vessels that acts like a strict doorman, only letting certain tiny molecules into the brain and keeping out most others.

“Nature has protected the brain very carefully from a lot of the external events going on in the rest of the body, but this makes it hard to get drugs in there,” Chris says. This is how antisense oligonucleotides (ASOs) have made a tremendous impact in the field: the ability to administer therapies into the spinal fluid allows the drug to go directly to the brain. While a lumbar puncture, or spinal tap, is not as simple as taking a pill, “it’s been game-changing to go straight to the neurons and other cells in the brain,” Chris says.

Sequencing of the human genome has also helped researchers uncover specific mutations that trigger a disease: these become potential targets for slowing the disease course or potentially preventing that disease from ever developing.

That’s how Biogen developed the first approved treatment for spinal muscular atrophy (SMA), the most common genetic cause of childhood death. SMA had no approved treatments five years ago. Now it has two. The first treatment is an ASO targeting the disease gene developed by Biogen in collaboration with Ionis Pharmaceuticals.

Another big step forward has been the use of advanced imaging technologies to identify biomarkers, objective measures of change in the brain. Use of these imaging technologies allow researchers and clinicians to see whether a drug is reaching its target and to get early indications if the drug is modifying disease progression before evaluating whether more long-term clinical endpoints are met.

“Imaging technologies, such as MRIs, have played a key role in the development of multiple sclerosis therapies,” Kate says. “We realized that we could evaluate MS lesions in the brain during clinical trials and could quantify those lesions and show if the potential treatments decreased the level of inflammation in the brain. Biomarkers take the guesswork out of assessing how effective a therapy is. There are now over 15 therapies for MS, and it’s on the backbone of being able to do these phase II studies with imaging of the brain.”

Advanced imaging techniques also let researchers make sure they have the right patients in the right trials. “We’re very invested in developing a potential treatment for Alzheimer’s, and imaging biomarkers ensure that patients who enter a trial have the amyloid plaque in the brain that is characteristic of Alzheimer’s,” Kate explains.

“Not only could we use this imaging to make sure the patients had the plaque, but we could also see if the investigational therapy was getting rid of that plaque,” Chris says. “Without that link, there were too many intermediate steps, and the antibody might not have gotten to the right place.”

Over time, researchers are discovering that seemingly insurmountable challenges in brain research may be more attainable than they once appeared. Biogen remains focused, investing in research to prevent or treat brain diseases once considered too difficult, too unpredictable or too risky to tackle. The brain’s complexity may seem infinite, but so, too, are the curiosity and drive of scientists learning about it, and the effort to convert that knowledge into potential treatments for disease.

“We are here to solve the problems of the brain,” Kate says. “They’re big problems that carry so much pain and suffering for patients and their families and friends. Someone has to do the hard work, and because we’re so passionate about this area, we’re willing to put up with risk and failure, not be deterred and come back to try again. It’s something that drives us every day: that we can make a difference in the lives of people with MS and SMA, and we hope to be able to make a difference in the lives of patients with ALS or Alzheimer’s disease.”

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