Until recently, the drug industry paid for the lion's share of research into brain and spinal cord disorders. That’s not the case anymore. Drug companies are leaving the neuroscience field altogether. We all know about Geron ditching its stem cell trial last fall to focus on cancer.
Why this is happening, and what the science community can do about it, are the topic of an essay in the current issue of Nature
by Martin E. Schwab and Anita Buchli, colleagues at the Brain Research Institute of the University of Zurich. The title of the essay is "Drug Research: Plug the Real Brain Drain."
Schwab is well known in the neuroscience world for his groundbreaking discovery of molecules that inhibit nerve growth in the spinal cord, and for finding the antibodies to block the inhibitors and thereby encourage regeneration. The Schwab lab
is a member of the Reeve Foundation International Research Consortium on Spinal Cord Injury
From the paper:
Treatments that could restore lost functions to people with such injuries would radically change their lives and decrease the burden to their families and social environment. The economic interest to drug companies and health insurers seems obvious. Yet drug companies have withdrawn from neuroscience, more so than from any other disease area. Last year, Novartis closed its preclinical neuroscience research facility in Basel, Switzerland. Pfizer, GlaxoSmithKline and AstraZeneca had already made similar moves. Merck and Sanofi are also cutting research on brain diseases.
Why are they dropping out? It quickly boils down to the bottom line: their investments haven’t paid off. "In the past 10–15 years," notes the paper, "dozens of clinical trials for stroke neuroprotection — involving thousands of patients — have failed."
This retreat, the authors note, comes at a time when hope and progress have never been more in synch.
Drug companies have pulled out of neuroscience just as our understanding of brain plasticity has exploded. The antiquated view of the central nervous system as a hard-wired supercomputer has been overturned; the brain and spinal cord now appear as dynamic and adaptable biological systems.
Large injuries to the brain and spinal cord are not repaired spontaneously, causing lifelong impairment. But scientists have recently developed experimental interventions that enhance nerve-fiber growth and regeneration in animals with massive brain injury. In experiments with rats, mice and monkeys, researchers (in our laboratory and others) have induced regrowth of injured nerve fibers in the brain and spinal cord by suppressing growth inhibitors — enough for the treated animals to regain lost functions.
Schwab and Buchli point out that clinical trials are here now, with more on the way. Schwab’s work with the Nogo antibody is being tested in Europe and Canada by Novartis. But why so much failure? Partly it may be the way success is defined, with too much of a one-size-fits-all approach. Injuries and diseases are not consistent or uniform and there are huge variations in treatment responses.
A treatment might be missed, too, because the way it is measured is too coarse and not standardized.
Another problem with past trials was that the often crude clinical endpoints missed small but meaningful treatment effects, such as improvements in hand, leg or bladder function. With novel approaches, we can do better.
What can be done? The authors first suggest that the field be reinvigorated by collaboration and exchange:
If researchers collaborate from the outset, they are more likely to produce a drug that works6. For instance, they could establish a set of criteria to evaluate a particular therapy in both animals and humans, so that what seems to work in one is more likely to seem to work in the other. Newer diagnostic tools will enable scientists to identify which subgroups might benefit most from a specific therapy.
Since money is the central issue here, Schwab and Buchli suggest two things: use what we have more wisely and seek new partners for funding:
Instead of investing billions in one drug, let’s spread funding among smaller, proof-of-concept trials for compounds with good preclinical evidence. By focusing on well-selected populations (with tens of patients, not hundreds) and concentrating on a few centers, such trials would cost a few million euros rather than the €50 million (US$67 million) or more needed for one large trial. If smaller trials can bring a promising compound to an advanced stage, industry may then be willing to take it to market.
Where are there untapped resources with an interest in this sort of major public health issue? How about insurance companies, which spend up to €2 million [$2.6 million] for each patient with a spinal-cord injury. "A drug that could lower a patient’s disability would save insurers huge amounts."
The paper notes that In 2009, the top five US health insurers had profits of $12 billion. An investment of even a small percentage of that could result in a "true win–win situation."
The stakes are extremely high for society, the authors argue. They cite a study last year that reported cancer research being funded at about the same level as the neurosciences, but that brain and spinal cord disorders “are a greater socioeconomic burden than cancer, cardiovascular diseases and diabetes combined.” Clearly, it is time to unplug this drain.