In this essay, Alice Lazzarini, PhD, discusses her work on discovery of the alpha-synuclein genetic mutation and her own experience since being diagnosed with Parkinsonís disease.
For years I only saw Parkinson's disease through my microscope; now Parkinsonís is there every time I look into the mirror.
In 2004, I was working on a drug for Parkinsonís at a large pharmaceutical company when I began developing symptoms of the disease. Like many people do, I initially reverted to denial. I chalked the evidence up to being too immersed in the disease research. Acceptance began to take hold only once I realized that my perspective from both sides of the white coat was a story worth telling, that I could use it to speak out in support of Parkinsonís disease awareness.
During the 1980s, I coordinated a service program, the New Jersey Huntingtonís Disease Family Service Center. Then, in 1990, Dr. Roger Duvoisin, Chair of the Department of Neurology at Robert Wood Johnson Medical School at that time, recruited me to study neurogenetics.
Until the 1990s there had been little credence to Parkinsonís being genetic. For our 1994 paper in the journal Neurology (ďA clinical genetic study of Parkinson's disease: evidence for dominant transmissionĒ), I reviewed hundreds of medical records from Dr. Duvoisinís Parkinsonís patients. That publication helped to turn the tide of thinking toward a genetic component. Then, finding a rare family in which the disease was passed from generation to generation ultimately reversed the fieldís position.
Dubbed the ďContursi kindred,Ē the family originated from a little village southeast of Naples, Italy. Over the generations, there had been more than 50 family members with Parkinsonís, but there were 10 from whom we could collect DNA. Comparing samples from those ten to those of their unaffected relatives gave us the statistical power to locate a causative gene.
Dr. Duvoisin arranged collaborations with researchers at the University of Naples and at the National Human Genome Research Institute, part of the National Institutes of Health (NIH). In July 1996, I traveled to Contursi to collect samples needed to confirm preliminary results reported by the NIH lab. The Contursi kindred allowed us to identify the location of the first Parkinson's disease-causing mutation. This was a breakthrough that would change the future of Parkinsonís research.
I was thrilled when our discovery made The New York Times. The November 15, 1996 headline read ďScientists Identify Site of Gene Tied to Some Cases of Parkinsonís.Ē That same day, the NIH held a press conference at the National Press Club in Washington, DC, where we announced the publication of our discovery to the scientific community.
Within a few short months we determined that the Contursi mutation was in the gene that coded for the protein alpha-synuclein, which was soon thereafter recognized as the major component of the classic hallmark of Parkinsonís disease, the Lewy body.
Identifying a disease-associated gene and the pathways it affects is the first step in the development of novel therapeutics. After our discovery of the alpha-synuclein mutation, millions of dollars poured into research laboratories throughout the world in an effort to determine the role of alpha-synuclein in Parkinsonís disease.
The Michael J. Fox Foundation has supported much of that research, such as toward a vaccine to target alpha-synuclein and compounds to clear out Lewy bodies. The scientific and patient communities believe that targeting toxic alpha-synuclein might block its ability to spread between cells, forestalling and ó dare we hope ó reversing the course of Parkinsonís.
It has been nearly 20 years since our genetic discovery, and we are at last witnessing its potential to directly impact people with Parkinsonís. Whether or not this will have a therapeutic benefit for me remains to be seen, but I get immense personal satisfaction from seeing our research come full circle.
So what do I see now when I look in that mirror? I see a face thatís begun to mask. I see a tremor that I canít control, and I see a body that moves with a great deal more effort that it once did. But when I talk to that reflection, I can now say, ďOf all times to be staring down Parkinson disease, we are living in the most promising.Ē
Alice Lazzarini, PhD, is a clinical assistant professor in neurology at Rutgers-Robert Wood Johnson Medical School. She is the author of ďBoth Sides Now: A Journey from Researcher to Patient.Ē