Feb. 27, 2015
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 Parkinson’s disease.
For years I only saw Parkinson's
disease through my microscope; now Parkinson’s is there every time I look into
the mirror.
In 2004, I was working on a drug for
Parkinson’s 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 Parkinson’s disease awareness.
During the 1980s, I coordinated a
service program, the New Jersey Huntington’s 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 Parkinson’s being genetic. For our 1994 paper in the journal Neurology
(“A clinical
genetic study of Parkinson's disease: evidence for dominant transmission”),
I reviewed hundreds of medical records from Dr. Duvoisin’s Parkinson’s
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 field’s position.
Dubbed the “Contursi kindred,” the
family originated from a little village southeast of Naples, Italy. Over the
generations, there had been more than 50 family members with Parkinson’s, 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 Parkinson’s research.
I was thrilled when our discovery
made The New York Times. The November 15, 1996 headline read “Scientists
Identify Site of Gene Tied to Some Cases of Parkinson’s.” 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 Parkinson’s 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 Parkinson’s 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 — dare we hope —
reversing the course of Parkinson’s.
It has been nearly 20 years since our
genetic discovery, and we are at last witnessing its potential to directly
impact people with Parkinson’s. 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 that’s begun to mask. I see a tremor that I can’t
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, “Of all times to be
staring down Parkinson disease, we are living in the most promising.”
Alice Lazzarini, PhD, is a clinical
assistant professor in neurology at Rutgers-Robert Wood Johnson Medical School.
She is the author of “Both Sides Now:
A Journey from Researcher to Patient.”
