All scientists stand on the shoulders of those who came before them.
For decades, Dr. George Kraft, emeritus Alvord Professor of MS research, emeritus Professor of Rehabilitation Medicine and Neurology, and a Faculty Member with the UW Medicine Institute for Stem Cell and Regenerative Medicine (ISCRM), has been at the vanguard of discovery in the field of multiple sclerosis (MS) research. His name is attached to landmark studies that have shaped how people with the debilitating disease are diagnosed, cared for, and treated.
And yet, even Dr. Kraft looks up at the stars.
Multiple sclerosis is an immune mediated disease that causes neurological damage when the immune system attacks the nerve, usually the myelin sheath, the fatty tissue that coats nerves cells connecting the brain and spine to the rest of the body. Symptoms of MS, which can strike at almost any age, include fatigue, weakness, sensory loss, impaired coordination, pain, cognitive impairment, and vision loss.
In fact, there are several types of MS, which present as either progressive or relapsing. Approximately 85% of patients with MS have a relapsing form of the disease in which flare ups trigger temporary symptoms. In the other 15% of cases, the disease progresses, steadily eroding the myelin sheath and the nerve cells themselves.
While drug treatments for are available, they are expensive and are more effective at suppressing symptoms and slowing disease progression than addressing the root problem. Complicating matters further, diagnosing which type of MS a patient has is a trial-and-error process, costing precious time and money.
Dr. Kraft began his marathon effort to ease the torment of MS in the late 1970’s, when he answered a call from federal agencies to take up the fight against the disease. Over the next thirty years, Dr. Kraft would become a pioneer in MS research, launching the first comprehensive MS clinic on the West Coast (now the UW Multiple Sclerosis Clinic) and, during the second half of that period, serving as director of the MS Rehabilitation Research and Training Center (MSRRTC). A long the way, he would publish the first study establishing fatigue as the most common symptom of MS and develop a deep conviction that research and clinical care must go hand-in-hand.
Clinical care did improve during this time. New drugs became available. And new approaches to rehabilitation helped patients adapt to life with the disease, allowing more people to continue walking, and working, despite challenges with mobility and cognitive functioning. Yet, millions of Americans, and far more worldwide, continued to suffer from what Dr. Kraft calls hidden disabilities.
Then, in 1998, the phone rang.
Dr. Keith Sullivan, an immunologist with the UW and Fred Hutchinson Cancer Research Center (FHCRC), was calling with a single question. “Do you want to cure MS?”
In their ensuing research, Dr. Kraft and his collaborators from Fred Hutch followed in the footsteps of Dr. E. Donnall Thomas, the Nobel Prize-winning physician and researcher whose bone marrow transplants in leukemia patients were the first use of stem cells in human medicine. Indeed, Dr. Thomas had hired Dr. Sullivan to use stem cell transplantation methods to treat other diseases, including MS.
In stem cell transplant procedures, doctors harvest and freeze blood-producing stem cells from a patient’s bone marrow. Then, immunosuppressive techniques are used to destroy the patient’s faulty immune system, a perilous, grueling process that nearly kills the person it is intended to save. Finally, the frozen stem cells are returned to the body, where they attempt to reboot the immune system.
“We found 24 patients with all types of MS,” recalls Dr. Kraft. “Almost all of them were in the later stages of the disease. We didn’t know how they would respond to the stem cell treatment. We found that only one patient responded well – the only one who had the relapsing type of MS. That told us we had to intervene earlier, while patients were still relatively healthy.”
Nonetheless, the study drew attention. In 2002, Dr. Kraft presented the findings at the American Academy of Neurology conference in Denver, and an article on the research effort was published by the American Society for Hematology in 2003.
Dr. Kraft and researchers pushed ahead, determined to show that Dr. Thomas’s groundbreaking stem cell transplants could be a viable model for the treatment of MS. There were reasons for optimism. New methods were making the transplant procedure less traumatizing and the immunosuppressive technique was modified to be gentler on the body.
The next study, completed more than a decade later, set an audacious goal. Not content with incremental progress, the research team set a target known by the acronym EFS – event-free survival. Once again, the strategy was a one-two punch to the disease: a high-dose immunosuppression therapy (HDIT) followed by blood stem cell transplantation.
This time, the results, published in Neurology in 2017, were much more encouraging: three years after the procedure, event-free survival was 78%, meaning that more than three out of four patients experienced an absence of progression, relapse activity, or new MRI lesions. At four years it was 73.8%, and at five years 69.2%.
It was a moment to celebrate: the same procedure that offered hope and healing to thousands of cancer patients was pointing to a brighter future for patients coping with the relapsing forms of MS.
The authors called for further investigation to demonstrate the effectiveness of the procedure relative to other treatment options, like drugs. Less than two years later, a comparison study published by the Journal of the American Medical Association affirmed that the one-time treatment was “more effective for patients with relapsing MS than drugs and can be performed with tolerable toxicities.”
The work, of course, is not done. This spring, Dr. Kraft will present research on new diagnostic approaches that will help doctors pinpoint which type of MS a patient has, suggesting which course of treatment to pursue. And, more rounds of trials will take place, each bringing the world one step closer to life-changing treatments.
One grace-note to the story came, not at the end, but shortly after Dr. Kraft presented the early results in 2002. He was invited to give a lecture at Fred Hutch. The lecture hall was bustling with scientists. Yet, the first row of chairs were empty, except for one curious audience member: Dr. E. Donnall Thomas, the University of Washington researcher whose groundbreaking bone marrow transplant procedure became a model for new treatments of MS.
It was a satisfying moment, capped by a pleasant conversation with Dr. Thomas. Reflecting on his entire journey, however, Dr. Kraft goes all the way back to the beginning. “I have been asked what has motivated me and been most gratifying. The most consistent motivator has been curiosity and the pleasure of learning how the world works. As a child, I enjoyed taking things apart to understand them. As an adult, I am very intrigued by how disease works, and how understanding those mechanisms can help us diagnose a disease, treat it, and make a difference in the life of a patient.”