The power of basic neuroscience: Unlocking new treatments for neurological conditions
Despite years of research, many neurological disorders remain a challenge. So, it's no surprise that when discussing the value of scientific exploration, some question its practical outcomes. "Basic neuroscience hasn't produced new drugs," they argue. But here's where it gets controversial...
While it's true that many medications have ancient origins or were discovered by chance, there's a growing list of drugs that owe their existence to basic research. Take zuranolone for postpartum depression, suzetrigine for pain, and the gepants for migraines - these medications are the direct result of insights from the lab.
These success stories are crucial. They prove that neuroscience research can lead to life-changing treatments. Especially now, when public funding for basic research is facing cuts and restrictions, highlighting these achievements is more important than ever.
For instance, the development of zuranolone began with an observation about allopregnanolone, a naturally occurring steroid. Researchers found that allopregnanolone levels in the rat brain spike during pregnancy, but drop dramatically just before birth. This led to the bold idea: Could restoring these levels help treat postpartum depression? Clinical trials proved this concept right, and in 2019, the FDA approved brexanolone (Zulresso) and later zuranolone (Zurzuvae) for this purpose.
Similarly, basic neuroscience research led to a new, non-opioid pain drug. By studying sensory neurons and their action potentials, scientists discovered an extra sodium channel type called Nav1.8. Blocking this channel without affecting brain activity offers a unique way to manage pain without the risks of opioid addiction. This insight led to suzetrigine (Journavx), approved by the FDA this year for short-term pain relief.
And this is the part most people miss: Sometimes, the simplest observations can lead to the biggest breakthroughs. For example, the discovery of calcitonin gene-related peptide (CGRP) in the 1990s inspired a new class of migraine therapies. CGRP is produced in abundance by rat trigeminal neurons, and when released, it stretches vessel walls, triggering a painful feedback loop. Targeting CGRP receptors has led to safer and more effective migraine treatments.
Other examples include fezolinetant (Veozah) for menopause symptoms, ziconotide (Prialt) for chronic pain, and L-DOPA for Parkinson's disease. Basic research has not only discovered new mechanisms but also guided the development of drugs with better brain distribution and fewer side effects.
So, why aren't there more success stories? The answer is complex. Even with the right biological insights, drug development can fail due to various reasons. But by learning from past successes and improving translation, we can increase our chances of success.
Progress often comes from delving deeper into biology, as seen with the identification of CGRP. While animal models have their place, sometimes the most powerful clues come from simple measurements, like allopregnanolone levels. We don't always need to fully understand a disorder's causes; sometimes, finding the right intervention point is enough, as shown with Nav1.8 and pain management.
Additionally, conditions with clearer definitions, like postpartum depression, offer more focused entry points for treatment development. The recent success stories emphasize that translation takes time. Many of these breakthroughs began with discoveries in the 1980s and 1990s, yet it's only now that approved treatments are reaching patients.
The history of basic neuroscience proves its potential. With the pace of discovery accelerating, I believe we're on the cusp of seeing more basic research translated into new medicines. But this promise relies on sustained public investment. Basic neuroscience discoveries are the foundation for future medical breakthroughs.
