Research Award Article

ASAP has taken an important step forward in the drive to "Find A Cure", by awarding grants to three distinguished researchers. The recipients, Dr. Frank Loth at the University of Illinois-Chicago, Dr. Joshua Adler at Wayne State University and Dr. Mary Eaton at the University of Miami will each receive a one year, $50,000 grant to pursue research focused on syringomyelia.

The research grants are the culmination of a process, defined by the Research Committee, which started with a call for proposals. By advertising in major journals, posting on the ASAP web site and through a direct mailing to medical schools, ASAP was able to attract a wide range of quality proposals. Proposal topics included: mechanisms of syrinx formation, numerical modeling of cerebrospinal fluid (CSF) flow, investigations into the development and treatment of chronic pain, a clinical study evaluating failed Chiari surgeries and the development of software to aid in visualizing a syrinx.

Each member of the research committee, Dr. Marcy Speer, Dr. Richard Ellenbogen, Richard Jelley and Rick Labuda, rated the proposals on significance of work, medical and scientific merit, principal investigator, research environment and collateral financial support. The ratings served as a basis for several spirited discussions where the committee tried to balance the strength of the proposals, the needs of ASAP members and the desire to build a broad portfolio of research. The committee then ranked the proposals and made a funding recommendation to the Board.

It is the hard work and generous spirit of ASAP members that enabled these grants. Everyone that raised money, donated money or raised awareness is a participant in these research projects and hopefully will share the pride and excitement of the Research Committee when reading about them.

Importance of the Mechanical Forces in the Development of Syringomyelia for Patients with Chiari Malformation

Dr. Frank Loth, Assistant Professor in the Bioengineering Department at the University of Illinois-Chicago, attended the ASAP conference last summer and came away impressed. "The level of patient interest and involvement with syringomyelia is amazing. There is such a strong desire to understand the condition and a great willingness to work towards making a difference; it gets me excited as a researcher." As a mechanical engineer, Dr. Loth is also excited about the new approaches he can bring to a condition historically reserved for neurosurgeons, neurologists and radiologists.

The proposal Dr. Loth submitted to ASAP builds upon his previous work in this area. His team at UIC has developed software which uses MRI data to build a patient specific, mathematical model of CSF in the region around a Chiari malformation. Now, Dr. Loth wants to investigate the role pressure plays in syrinx formation, progression and regression. To do this, he will build physical models that closely match the human body's spinal canal and recreate the conditions present in syringomyelia. The models will allow him to experiment in a way not possible inside the human body. Using MRI data obtained from a Chiari/syringomyelia patient, Dr. Loth will build two models of the spinal canal and cord, one before and one after a decompression surgery. With the models, Dr. Loth will study how the fluid in and around a syrinx behaves with a focus on analyzing the pressure around the syrinx.

If Dr. Loth's ideas are correct, then studying the pressure environment in the spinal canal may be the key to understanding the development of syringomyelia. Armed with this knowledge, physicians may be able to refine their surgical techniques, predict when a syrinx will form or regress and develop entirely new treatment options.

Cytokines and Neuropathic Pain in Syringomyelia

Dr. Joshua Adler knows a lot about pain; he has been studying it for 20 years. Currently an Associate Professor of Neurology at Wayne State University and also the Director of Pain Services at the Detroit VA, Dr. Adler knows that pain comes in many shapes and sizes. "With my work at the VA, I have dealt with all kinds of pain. Certainly one of the most difficult and frustrating types of pain is the neuropathic, or central pain, associated with syringomyelia." Dr. Adler has spent many years investigating pain at the molecular level, but in the last couple of years is focusing on using animal models to study the causes of chronic pain.

Dr. Adler proposes to use an animal model to investigate the role of cytokines in neuropathic pain associated with syringomyelia. According to On-line Medical Dictionary, a cytokine is a protein, released by cells of the immune system that acts as a mediator in the generation of an immune response. Dr. Adler hypothesizes that neuropathic pain in syringomyelia is mediated by cytokines, which either increase, or cause abnormal distribution of, pain associated peptides. In fact, Dr. Adler's preliminary data suggests that one cytokine, interleukin-1, leads to an increase in substance P. As written about previously in the newsletter, substance P has been associated with central pain, and abnormal distribution of substance P has been found post-mortem in people with syringomyelia.

Specifically, Dr. Adler will create syringomyelia in rats through chemical injection. Once he verifies that the rats are showing signs of neuropathic pain, he will examine them for increased levels of interleukin-1, substance P and several other substances. With his research, Dr. Adler hopes to piece together the molecular chain of events that leads to chronic, neuropathic pain. If he is successful, the implications are profound. Dr. Adler notes that there are already substances available on the market, being used for other purposes, which may be able to break the chain of events leading to neuropathic pain and finally bring some relief.

Pre-clinical Development of GABA Cell Therapy for Chronic Pain After Spinal Cord Injury

From her time spent as a military, critical-care nurse, to her world travels, to her current work as an Assistant Professor of Neurological Surgery at the University of Miami, Dr. Mary Eaton has had a good look at what chronic illness does to people's lives. "From my experiences, I have developed a strong empathy for people suffering from chronic illness and have established a real human connection with many people affected by spinal cord injury". Driven by the human side of the equation, Dr. Eaton has spent the last eight years studying pain in spinal cord injury.

Backed by the resources of the Miami Project To Cure Paralysis, Dr. Eaton's research is focused on developing cellular 'minipumps' that can be injected near pain processing areas of the spinal cord to both alleviate and potentially eliminate chronic, neuropathic pain. In her proposal to ASAP, Dr. Eaton will develop cells that secrete (or pump) GABA, a naturally occurring neurotransmitter in the spinal cord that inhibits pain, and inject the cells into rats with spinal cord injuries. Dr. Eaton's research suggests that in a severe spinal cord injury, not enough GABA is produced to cope with the injury, and chronic pain ensues. Dr. Eaton hypothesizes that inadequate GABA can be compensated for by injecting a 'minipump' of cells that secrete GABA near the injury. After developing the GABA secreting cells, Dr. Eaton will study how well they produce GABA in rats with spinal cord injuries and whether the increased GABA reduces indications of neuropathic pain.

If Dr. Eaton's ideas prove out, she intends to move on to human, clinical trials. With no effective treatment currently available for people suffering chronic, neuropathic pain, Dr. Eaton's work offers hope that one day, relief may be as easy as getting a 'minipump' injection.

Just The Beginning…

These three projects demonstrate what can be accomplished with the funds raised by you, the ASAP members. Be proud, be excited, for these are just the beginning.