It started at the end of a long day. Jessica Panzer, MD, PhD, then just a few weeks into her pediatric neurology residency at The Children’s Hospital of Philadelphia, was about to go home. Instead, she was called to the emergency room to consult on a 3-year-old girl who could barely walk. What happened then opened up new questions in her budding research career.
Not long after that, Miriam Rosenberg, PhD, started on a convergent path when her own 19-month-old daughter got sick. The toddler first developed problems with excessive drooling and stumbling while she walked. Within a few months, she had a sudden onset of more severe symptoms — unable to walk, severe tremor, unable to feed herself. Dr. Rosenberg and her husband brought their child to the nearest hospital.
Several months and multiple hospitalizations later, after Dr. Rosenberg and her family moved to Israel for her current position as a scientist at the Weizmann Institute of Science, doctors identified her daughter’s condition as an autoimmune disease called Opsoclonus Myoclonus Ataxia Syndrome (OMAS). OMAS is so rare that many clinicians can go their entire careers without ever seeing a case.
On the other side of the world, Dr. Panzer fortunately recognized her own patient’s strange, jerky eye movements, known as “opsoclonus” and sometimes colloquially called “dancing eyes.” Once she diagnosed OMAS, she prescribed immune drugs to diminish the body’s attack on its healthy neurons, and the child’s symptoms improved.
Each scientist found herself with more questions than answers. OMAS is so little understood that its treatment remains tricky. The pair has now teamed up to lead a research project seeking the underlying cause of OMAS, with a recent grant from the Pablove Foundation. A recent article in CHOP’s Bench to Bedside research newsletter goes into further details about their study.
No Standard Treatment, No Test
When Dr. Panzer’s OMAS patient started having problems in rehab, she realized she had little clear advice from other medical professionals on what to do.
“There was no test I could do to see if she was really flaring up or not, and there were no studies to say what treatment we should give at this point if she was flaring up,” Dr. Panzer said. “How can we not know what to do with this disease? That’s how I got interested in doing research in this area.”
Dr. Panzer first teamed up with Angela Waanders, MD, MPH, then an oncology fellow at CHOP and now an attending physician specializing in neuro-oncology. The pair focused on improving clinical treatment plans for patients with OMAS, about half of whom also have the nerve-cell tumor neuroblastoma. (The cancer is believed to trigger the autoimmune response.) The two young doctors started treating OMAS patients in a standardized manner and writing protocols based on the best-available information so that other clinicians could follow or refine their methods.
Then, as the end of her pediatric neurology residency neared, Dr. Panzer sought the advice of Josep Dalmau, MD, PhD, a neurologist and autoimmune disease expert then at the University of Pennsylvania, to develop a residency research project focused on OMAS. Dr. Dalmau encouraged her to try to find the antigen that triggers the immune response in OMAS. Scientists need to fundamentally understand how the disease works to have the best hope of interrupting the process with targeted treatments, or monitoring its status with a lab test.
The results of that residency research project were published this summer in the Journal of Immunology and provide a promising hint that the antigen that triggers OMAS may be detectable. Dr. Panzer is about to carry this research into the next phase.
She will not be doing it alone.
A Daughter’s Dancing Eyes Inspire New Scientific Approaches
While Dr. Panzer was getting familiar with OMAS from treating patients and doing preliminary lab research, Dr. Rosenberg was seeking answers about her own daughter’s disease. She used her scientific training to ask deeper questions than most parents could.
In February 2014, Dr. Rosenberg attended a conference of OMAS researchers in the United Kingdom, the biannual Dancing Eye Syndrome Support Trust symposium. She learned about the state of the OMAS research from presenters who were mostly focused on clinical questions and approaches.
“At the conference, I had the realization that people weren’t answering the molecular and biochemical questions that my training would lead me to ask,” Dr. Rosenberg said.
She went home and wrote her first grant to study OMAS.
At the same time, she and her husband were focused on their daughter’s treatment. As a result of their persistence, doctors eventually found that the child had a neuroblastoma that was missed on her original scans. She had surgery just after her third birthday and is now doing well — cancer-free with only some mild OMAS symptoms.
Dr. Rosenberg’s scientific curiosity about the disease persisted. Her first grants were not funded. Before she tried again this year, she contacted John Maris, MD at CHOP, to discuss a potential collaboration. She knew him as a leader in the field who had an outstanding track record with neuroblastoma therapeutics and a deep knowledge of genomics. Dr. Maris, an attending physician and Giulio D'Angio Chair in Neuroblastoma Research at CHOP, and a professor of pediatrics at the Perelman School of Medicine at Penn, knew exactly which CHOP doctor she should talk to about an OMAS study.
Dr. Rosenberg’s collaboration with Dr. Panzer was born.
Different Disciplines, Different Insights
As the pair gets started on their research together, they are drawing on the insights of their different scientific backgrounds and those of their collaborators: Dr. Waanders’ neuro-oncology, Dr. Maris’ neuroblastoma and molecular genetics, Dr. Dalmau’s neuroimmune expertise, and clinical trial insights from Pedro de Alarcon, MD, of the University of Illinois.
“Both of the experiments I proposed are basically things where you get back a long list of molecules and make sense of them,” Dr. Rosenberg said. “Different people recognize different things based on their background and training in different areas of biology.
“It’s an all-star team. I hope this will be a really truly interdisciplinary collaboration success story.”
To learn more about the research this team will do, read the story in Bench to Bedside.