"Neurological disorders have always challenged the best efforts of medicine," says Dr. Audrey Penn, deputy director of NINDS. To her, the nervous system, with it intricate workings, is the most fascinating component of the human body. But when circuits in the system begin to go haywire, the real challenge is caring for disabled patients suffering from progressive, debilitating and often chronic disorders.
"Neurological disorders are disabling, which is a real put off for a lot of people including physicians," Penn said. "Some don't like to deal with people who are that disabled, who can't walk, can't see, and have loss of balance. I'm not as bothered. We have over 30,000 neuroscientists who study how the brain, nerves and spinal cord work - that's the intellectual part. But if you're one of the 18,000 neurologists, you can't rest on that part; you have to take care of people."
Colleagues in other areas of medicine claim neurologists are all intellect and no medicine, "diagnose and adios", Penn said, because our understanding of the nervous system has been a long time coming.
"The intricacy of the brain is awesome, its workings are elusive, and an extraordinary variety of disorders affect the nervous system. Furthermore, the brain and spinal cord are difficult to access, sensitive to intervention, and reluctant to regenerate following damage. However, building on advances in basic science, progress is improving peoples' lives, and prospects for the future are even more encouraging. We are working to engage the best minds in the nation and provide them with the resources they need to devise ways to prevent, treat, or, ultimately, cure neurological disorders," Penn said.
Progress is being made on several fronts. There were 250,000 fewer deaths from stroke in the United States in the past year due to advances in prevention. By challenging people to lose weight, control their blood pressure, stop smoking, and be aware of lesser known risk factors, such as some birth control pills, the public has taken an active role in preventing stroke. New therapies such as tPA, also known as the clot buster, work well by dissolving blood clots, the cause of most heart attacks and strokes. The use of carotid stents to prevent stroke is proving to be a viable option over traditional endarterectomy (see story on page 1).
Penn and her colleagues at NINDS outlined other advances in neurology in their 2004 budget request to the Department of Health and Human Services. They include:
o Birth defects that affect the nervous system are on the decline due to a public awareness campaign to get women to take folic acid prior to conceiving.
o Genetic counseling for inherited disorders, such as Tay-Sachs disease, are also having a major impact on public health.
o Cortico-steroids, the first acute treatments for spinal cord injury, have proven effective for reducing neurological damage.
o Immune therapies now reduce relapses and slow the progression of disability in multiple sclerosis.
o Surgical options employ implantable devices to compensate for brain circuits unbalanced by disease in Parkinson's disease and epilepsy.
o Enzyme therapies have brought the first successes in treating lipid storage disorders.
o Advances in molecular genetics and brain imaging are further augmenting clinicians' insights to diagnose and to guide therapy.
"Progress is gaining momentum, with an unprecedented variety of new treatment and prevention strategies under development," Penn said citing in her budget request examples such as drugs to hone in on the molecules that cause disease, stem cell therapies to replace lost nerve cells, neural prostheses to read control signals directly from the brain, immune tolerance approaches to prevent stroke, therapies to repair or replace defective genes, and behavioral interventions to encourage the latent "plasticity" of the brain and spinal cord toward self-repair.
"Each of these strategies relies upon remarkable advances in understanding how the normal nervous system works and what goes wrong in disease," Penn said.
Penn and her colleagues outlined in their budget request some of the more interesting scientific achievements of the past year, which include:
Scientists studying genes discovered a mutation that causes a form of Charcot-Marie-Tooth disorder, a common disabling disease of peripheral nerves; pinpointed the site of a gene contributing to autism; and found clues about how a chromosome defect causes facioscapulohumeral dystrophy, a common form of muscular dystrophy.
In animal models of human disease, themselves often the product of gene research, gene therapies have yielded encouraging results for neurofibromatosis, Fabry disease and Parkinson's.
Scientists on the trail of cell therapies discovered that primitive precursor cells in the adult rat brain can respond to experimental damage by multiplying, migrating to the site of damage, and making new nerve cells, and that transplanted embryonic stem cells show promise in animal models of Parkinson's disease, stroke, and other disorders.
Scientists focusing on the immune system found that a strategy, which suppresses immune reactions, prevents strokes in hypertensive rats; that an anti-cholesterol drug, the statin Lipitor, reduces symptoms in an animal model of multiple sclerosis; and that the gene defect in Batten disease may result in unexpected immune reactions, which could contribute to the devastating consequences in the brain.
In research on drug treatments, the antibiotic minocycline slowed progression of amyotrophic lateral sclerosis in mice; the natural brain chemical inosine stimulated rewiring of the brain following stroke in rats; and coenzyme Q10 may slow progression of Parkinson's disease.
Scientists studying new technologies developed a device that enabled rats to control a robot arm just by thinking about it; devised better ways to delivery therapeutic agents to the brain; used microarrays to monitor the activity of thousands of genes, yielding insights about brain tumors and multiple sclerosis; and for the first time, recorded activity of the human fetal brain in response to light, which may lead to better prenatal diagnostics.
Penn believes that future research will need to involve multiple disciplines including engineers, chemists, physicians, and clinical researchers in order to achieve goals more quickly and to share results and materials.
"All of it means networking. More teams, fewer single explorers," she said.
Of course, the hot topic facing neurologists these days is stem cell research. The NINDS houses some of the more renowned scientists in this field of expertise. Their research focuses on stem cells from mice because they can get all they want as opposed to the limited use of human embryonic stem cells allowed by government. Penn said that stem cell research is in its infancy, regardless of where one's opinions lie in the debate.
"There's a lot of work to be done before it's going to be safe or feasible," she said. "The other problem is putting the stem cells into the body. How do you get them in the brain? We haven't even figured that out yet. It's step by step. There's so much that has to be done; it's not going to happen right away. We all think stem cells are in our future. But we're in the early stages."