David Irani, MD is an Assistant Professor of the Department of Neurology, Johns Hopkins Hospital. He is also the Co-director of the Johns Hopkins Transverse Myelopathy Center. Dr. Irani obtained his MD degree from University of Michigan (Ann Arbor) in 1987 and completed his internship at St. Joseph Mercy Hospital at Ann Arbor. He then came to Johns Hopkins Department of Neurology as a fellow in Neurovirology (1988-1990) and completed his residency training in Neurology. In 1993, Dr. Irani joined the faculty of the Department of Neurology at Johns Hopkins Hospital and has focused his research activities in neuroimmunology and neurovirology. He has been actively involved in studies of viral infections of the CNS and leukocyte trafficking.

Transverse myelitis (TM) remains a difficult problem from a variety of standpoints. Since it occurs relatively infrequently, even subspecialist neurologists may have little practical experience with the disorder. Since it may have many underlying causes (only some of which are uncovered at the time of the acute illness), predicting the long-term clinical outcome for an individual patient can be difficult. And since we are still quite limited in our capacity to promote meaningful neurologic recovery once the inciting event has subsided, physicians may have few treatments to offer their patients during later stages of disease. In the face of such obstacles, one might be tempted to conclude that conducting research on TM is an impossible task. Indeed, the disorder has been relatively neglected by the biomedical research community, perhaps for some of the very reasons described above. Nevertheless, my colleagues at Hopkins and I have initiated a comprehensive research effort to study TM in both the clinic and the laboratory. Our goal is to take advantage of new scientific developments in the fields of neuroscience, virology, and immunology to better understand TM. We hope to make advances that will translate into new diagnostic and treatment applications which can be used in the hospital and the clinic in the near future.

One approach we have taken in our research is to directly study TM as it occurs in humans. There are several important issues we are trying to tackle: enhancing our understanding of the underlying causes of TM, improving our ability to predict a patient's eventual clinical outcome in the earliest stages of his or her disease, and testing whether there might be ways to improve neurologic function well after the acute illness has occurred. One hypothesis we are examining is that many cases of TM are caused by viral infections that develop in the spinal cord; viruses that go undetected because the diagnostic tests needed to identify them are not available. As a result, we are looking for novel viruses in the cerebrospinal fluid (CSF) of patients with acute TM using new laboratory techniques. We have already found that certain proteins which normally reside within nerve cells of the spinal cord are released into the CSF of some patients with acute TM. Detecting these proteins are clues to us that the underlying cause of TM in those cases is quite severe (the nerve cells are actually being damaged and are releasing these proteins). As a result, this assay may serve to help us predict how much function a given patient will eventually recover during the earliest stages of TM. We also plan to look for alterations in the immune systems of affected patients that may have made some of them susceptible to TM. We suspect that part of the susceptibility of certain patients to TM resides in the unique way that their immune systems respond to certain infections. To try and promote delayed recovery in patients well after their acute TM, we plan to test the effectiveness of drugs that increase the transmission of electrical signals in the remaining intact spinal cord nerve cells. On the horizon may be the potential to grow nerve cells or precursors that turn into nerve cells (called stem cells) in culture dishes for implantation into the spinal cords of patients who have had TM. In this setting, it is hoped that the implanted cells can re-establish some of the connections that were damaged during the acute phase of the illness and promote some degree of clinical recovery. The groundwork experiments for such an approach are underway in experimental animals (see below).

Successful disease-related biomedical research is often best accomplished through the direct study of affected tissue. However, since performing spinal cord biopsies on patients with acute TM is both impractical and potentially dangerous, we do not have access to such samples. To circumvent this limitation, we have developed a model of TM in experimental animals caused by direct viral infection of the spinal cord. This has allowed us to study how and why nerve cells degenerate in this situation, and because affected animals become paralyzed to varying degrees, it has provided an excellent model system to test the effects of new therapies that might eventually show promise in humans. Thus, we are now trying to establish the experimental conditions under which stem cells can be implanted into the spinal cords of paralyzed mice and be coaxed into resprouting new nerve connections. We have also begun to figure out how to interrupt some of the signals that the virus uses to trigger the death of infected nerve cells in the spinal cord. We hope this may lead to the development of novel drugs that could exert the same effect in humans. While we realize that the use of laboratory animals in biomedical research is highly controversial, there simply is no other way to answer the kinds of questions we are asking. Overall, while research progress is slow, we feel that we have already made some important observations and have plans to expand these efforts as future research support becomes available.

Despite some early optimism, it is fair to say that TM-related biomedical research is still in its infancy. Nevertheless, I believe that our laboratory efforts, in particular, will bear fruit in the foreseeable future. As clinicians in this field, it is the explicit goal of my colleagues and I to translate our laboratory progress rapidly, but safely, to therapeutic trials in human patients. We are actively working to increase awareness and support of our research efforts.