Janssen’s Husseini Manji, M.D., is working toward a world in which diseases like depression and schizophrenia are diagnosed quickly and handled without stigma. His team's discoveries in the lab may just get us there.
Of all the illnesses out there today, which one would you say is the leading cause of disability around the globe?
The answer may surprise you.
It’s depression, which, according to the World Health Organization, affects more than 15 million adults in the United States and more than 300 million worldwide.
One reason disorders of the brain are so particularly devastating: Due to the stigma attached to mental illness, many victims suffer for decades before seeking help.
But Janssen’s Husseini Manji, M.D., Global Therapeutic Area Head for Neuroscience, is on a mission to change that. He envisions a world where challenging illnesses as schizophrenia are viewed by the public—and treated by physicians—not as “personality issues,” but as the medical diseases science has revealed them to be.
Here, Dr. Manji discusses more about how he’s working toward that goal—and what we can expect next from his groundbreaking Neuroscience team at Janssen.
When it comes to understanding mental illness and treating it effectively, there's still much to learn. Why is that?
It’s fair to say that the brain is the most complex organ in the body. It’s not like the skin or other organs, where you can take a biopsy and figure out what’s going on.
That said, we’re living in the golden age of neuroscience, and thanks to brain imaging technology, we’re learning a staggering amount about normal brain function, as well as what’s happening with some of these common mental illnesses.
We function a bit differently from most neuroscience research organizations because we’re structured “end-to-end,” which means we do everything from basic lab to clinical research.
Since these disorders are so complex and challenging, we felt that it was important to have all types of research under one roof, which allows the clinicians working with people to talk to the scientists doing research and vice versa.
You’re focused on finding ways to identify mental illnesses as early as possible. Why is this so important?
A: Imaging studies have revealed that the longer you have depression or schizophrenia, the more damage it does to the brain. In depression and schizophrenia, for instance, we can show that parts of the brain shrink with lengthy or repeat episodes.
And with Alzheimer’s, we’re working on tracking subtle changes in people's eyes long before they develop symptoms. If we can create an eye test that identifies people at risk, we could potentially head off the illness before it does irreversible damage to the brain.
Early identification might work for schizophrenia, as well, because the illness often has what's called a prodromal period, when people start experiencing mild symptoms, like social withdrawal and perceptual abnormalities, before the disease fully sets in.
There's currently research being done with people who have a strong genetic risk factor for schizophrenia, with the goal of proving that if you intervene at an early stage you can get a much better treatment outcome—and potentially change the course of the illness.
You have also developed a new treatment approach for schizophrenia. How does it work?
Yes, it’s been on the market for just about two years. The single biggest predictor of relapse in schizophrenia is going off medication, but adherence is often poor because it requires going to a clinic, getting a prescription, getting the prescription filled and taking the medication as prescribed.
“My hope is that diseases of the mind will someday be viewed like any other illness —
no stigma, no shame, just support and sympathy.”
Dr. Husseini Manji
To help with these potential pitfalls, we developed an injectable drug that is given to patients four times a year. Over two years, just nine percent of people have relapsed. We have plans to develop a twice-a-year injection schedule, which will be even easier to adhere to.
What about treatments for depression?
All existing antidepressants work on the same premise by increasing the brain levels of serotonin and/or norepinephrine—neurotransmitters that act as messenger molecules between nerve cells in the brain.
But only about half of people get an adequate response from them, and it typically takes four to eight weeks or longer for someone to start feeling better. That’s far too long if someone is suicidal.
We’re studying a medication that works more quickly—in some people, within hours. It seems to block the activity of the receptors on a molecule called glutamate, the brain’s most prevalent neurotransmitter. It could be administered in a nasal spray, making it convenient to use.
We have received a breakthrough designation from the U.S. Food and Drug Administration for its potential use in people with treatment-resistant depression and in those who are suicidal. The designation means that the FDA will expedite the drug's development and review.
We’re very excited about this because we have the potential to save lives. There are at least 41,000 deaths every year in the United States from suicide, many of which result from untreated or poorly treated depression. Suicidal depression is a staggering public health issue: Only two forms of cancer have a higher death rate.
Your team is also investigating a second drug for depression. How does that one work?
It’s a medication that blocks a key inflammatory protein called interleukin 6 (IL-6).
There are many studies that support the idea that depression is an inflammatory disorder, so we’re giving IL-6 antibodies to depressed patients—half of whom have clear signs of inflammation in their blood, and half who don’t. We should have results sometime in late 2017.
What are your hopes for the future of neuroscience?
Research in neuroscience has slowed because we haven’t had any big breakthroughs. The same thing happened with cancer research, but then there were one or two breakthroughs, and now you can’t find a pharmaceutical company without an oncology group. We’re hoping to do the same for neuroscience.
Even as an undergrad, I was fascinated by the workings of the brain. Then, in med school, I learned about all of these devastating illnesses and it struck me as shameful that we have people with serious illnesses who, because of the stigma attached, have been marginalized and ostracized.
My mom suffered from depression, and although she wasn’t incapacitated, I saw how much suffering it can cause. By working to develop new treatments, we’ll encourage more people to seek help.
At the same time, when people learn that depression can be treated effectively, I believe the attitude toward mental illness will change. My hope is that diseases of the mind will someday be viewed like any other illness—no stigma, no shame, just support and sympathy.
This article, written by Ginny Graves, first appeared on jnj.com.