Update on Research at the Johns Hopkins Transverse Myelopathy Center
Chitra Krishnan

There is always a great deal of activity going on at the JHTMC. The most significant changes have been the addition of four new people to our staff. Peter Calabresi, MD is a close colleague of Dr. Kerr, is a neurologist, and recently joined the Hopkins faculty. He is the director of the Johns Hopkins MS Center (JHMSC). Dr. Calabresi is a well-known immunologist and is applying this training to the development of new treatments for MS. Dr. Calabresi is also an expert in running clinical trials. He and Dr. Kerr are already working on developing new treatments for acute TM and are working towards a clinical trial within the next 12-18 months.

Sanjay Keswani (MBBS) is also a new neurologist recruit onto the Hopkins faculty. Dr. Keswani's research and clinical interests have previously been HIV-related neurology and mechanisms of peripheral nerve degeneration. But we have convinced him that the study of TM is really where it's at! He is now beginning to investigate how axons get damaged in the spinal cord and will run the first human study in protecting those axons during the acute phase of TM.

Edie Goldberg (RN) is a nurse who has just joined the JHTMC. Edie was first a nurse and most recently came from Pfizer where she was one of the best hospital representatives in the entire country (this is important because it is always good to have an "in" with a big pharmaceutical company). Edie will run the clinical trials at the JHTMC and the JHMSC. She will also serve to assist with clinical matters of patients that Dr. Kerr has seen, i.e., medication refills, change in status, new symptoms, etc. Since it is sometimes difficult to reach Dr. Kerr, Edie (and I) can handle many of the patient's questions. Edie's addition to our staff will allow us to provide even better service to our patients.

Finally, Deepa Desphande (Masters degree in biology and biotechnology) has joined the JHTMC research team. She has joined us from Texas A and M University and will run the immunology projects in the lab. These studies have already begun to reveal fascinating insights into the acute inflammatory process in TM patients, giving us potential new therapeutic strategies to pursue.

We will provide a brief overview of our ongoing projects, using this as an update to the previous newsletter.

Continued Development of the Clinical Database of TM

• Includes over 400 patients with transverse myelitis
• Cross-sectional and longitudinal
• CSF, serological, radiological, clinical components

Clinical Classification Project of Monophasic TM

• Clinical Features
• Risk Factors
• Prognostic Factors
• Outcomes
• Scientific manuscript to be submitted this year

Recurrent TM

• 20% of all TM patients seen at the JHTMC are recurrent cases
• A particular antibody in the blood of some patients predicts a possible recurrent course
• Scientific manuscript accepted and will be published this year (Hummers, Krishnan et al., 2003)
• Clinical course and immunologic abnormalities in patients with recurrent TM
• Treatment Strategies

Pediatric TM

• Studying a possible correlation with immunization
• Clinical features
• Outcomes
• Scientific manuscript to be submitted this year

Risk Factors in the Development of TM

• Federally funded grant to study the frequency of particular events that occur prior to the development of TM
• We will compare the frequency of these events in TM and in other neurologic disorders to see if they are more common in TM patients
• If so, it provides us a lead in defining how these events may trigger TM

Spasticity Treatment Trial

• We want to develop better treatment strategies for spasticity in patients with TM since the regular treatment options (tizanidine, baclofen, diazepam) have problems, e.g., fatigue and sleepiness
• Tiagabine (Gabitril) vs. placebo
• Crossover design
• Potentially less sedating than baclofen, tizanidine, diazepam

Depression and Cognitive Impairment with TM

• We want to investigate the frequency and mechanisms of depression and subtle cognitive changes that occur in some people after TM
• Funded clinical trial (run by Dr. Adam Kaplin) that is now enrolling patients in the acute phase of TM
• Novel neuroimaging-magnetic resonance spectroscopy-and cytokine profiles to assess pathophysiology

Novel Imaging of The Spinal Cord

• We want to investigate a better strategy to image the spinal cord
• We are developing a new MRI protocol (magnetization transfer) that may help to define the extent of inflammation in the spinal cord and how much damage is occurring
• If this technique does give us a better understanding of the spinal cord process, it may allow us to identify patients who need more aggressive treatment

Animal Model of TM

• We are trying to develop an animal model of TM
• Some early studies suggest that if we give a rat the same inflammatory proteins that are present in the spinal fluid of TM patients, they get weak
• This now gives us a way to test how the spinal cord gets weak

Stem Cells In TM

• Not near clinical trials
• But…
• In animals, we can protect from ongoing neural injury using stem cells
• We can now generate new motor neurons and coax axons to grow out of the spinal cord
• We are getting closer, but these studies are so expensive and we have not yet convinced the federal government to fund such studies.
• We will succeed, but not yet