Parkinson's researcher learning to live with the disease
MENDHAM – Parkinson's disease has pervaded Alice Lazzarini's life.
As a genetic researcher at Rutgers Robert Wood Johnson Medical School, she helped locate the first gene that leads to the formation of Lewy bodies—the hallmark of Parkinson's disease. Inside Lewy bodies are damaged proteins that kill cells the brain needs to send messages to the muscles.
That breakthrough made world headlines in 1996.
Seven years later, Lazzarini, at age 63, became a Parkinson's patient. Soon after, she retired.
In her new memoir, "Both Sides Now: A Journey from Researcher to Patient," she writes of the moment she realized what was happening to her. She was watching a DVD of Luciano Pavarotti singing in "La Boheme" and reminiscing about going to The Metropolitan Opera with her son.
"Suddenly, my right hand begins to shake," she writes. "It stops. It starts. Stops and starts. My hand is moving all by itself. 'Stop!' My hand obeys."
Though Lazzarini, who lives in Mendham, knew what was happening before her official diagnosis, it still shocked her. According to The Michael J. Fox Foundation for Parkinson's Research, only 10 percent of Parkinson's cases have been linked to a genetic cause. Lazzarini had no family history.
"But both my grandmothers died in their mid-40s," she said. "Who knows?"
It's the very problem that hampers genetic research on all neurodegenerative diseases that occur late in life, she explained: at the time older people are diagnosed, their ancestors are already dead and so unavailable for questioning or testing.
According to the Parkinson's Disease Foundation, only 4 percent of people with the disease are diagnosed before the age of 50.
In her memoir, Lazzarini offers rare behind-the-scene glimpses of what life was like for her as a researcher, mother, wife, and patient, including seminal work with the Contursi family, both in the U.S. and Italy. The family's genes led to the biggest breakthrough in Parkinson's research in more than 30 years. A total of 61 of 400 descendants of a couple who lived in Contursi in the late 17th century were found to have, or have had, Parkinson's.
"A family from which there were at least 10 blood samples available from affected individuals gives us the mathematical power to locate a given gene. It's a geneticist's dream," said Lazzarini, who recounts for her readers the story of one Contursi family member in the little Italian village, south of Naples, who at first refused to give a blood sample.
Her book, however, tells two journeys of adventure—one of scientific discovery, the other of self discovery. Though "Both Sides Now" was represented by a literary agent for some time, Lazzarini decided to self publish it in August for three reasons, all of them dealing with timeliness.
First, in July, AFFiRiS, an Austrian drug development company, held an international conference announcing that its PD01A Parkinson's vaccine had passed early clinical trials. The vaccine, for which trials will continue for at least another five years, is based on the discoveries of Lazzarini's teams.
"When I heard that, I couldn't sleep that night," she said. "I was so excited."
Maximizing dopamine
Like many Parkinson's patients, Lazzarini currently takes a Monoamine Oxidase B (MAOB) inhibitor, which helps raise the level of dopamine in the body. A month ago, she started also taking carbidopa/levodopa, a medication combination whose peak effectiveness lasts five years.
"I like to get out and walk in the morning, and I felt like I was walking through molasses," she said. "With carbidopa/levodopa, I have a smoother movement and I can actually walk."
Carbidopa helps prevent levodopa from breaking down before it gets through the blood-brain barrier. Once in the brain, levodopa is converted into dopamine.
Both treatments are an effort to retain or create dopamine, a neurotransmitter that helps the brain send messages to the muscles. As dopamine dwindles, so does control over movement. In latter stages of Parkinson's disease, even facial muscles are affected, resulting in what some have called an expressionless Parkinsonian "stone face."
Treating the cause
Lazzarini's research teams revealed the PARK1 genetic mutation, on Chromosome 4, that damages alpha-synuclein, a protein that normally is abundant in the human brain. When damaged, though, the protein misfolds, she explained. Consequently, the brain can't dispose of it.
Over time, damaged proteins cumulate inside Lewy bodies, clog the brain, and kill the cells that make dopamine.
Finding the mutation was "very groundbreaking," according to Dr. Thomas Zimmerman, a neurologist who was on Lazzarini's team at the medical school. Today he heads a Bernardsville-based clinical and regulatory consultant company for drug development.
"Alice is top drawer," he said, "in terms of her thinking, her research, and her approach."
Because the PD01A vaccine is attempting to prevent the formation of Lewy bodies from taking place at all, it has the potential to help people with all kinds of clinical manifestations of Parkinson's disease—those whose predominant symptoms are tremors (like Lazzarini), those whose predominant symptoms deal with cognition and balance, and those with more severe Parkinson-plus syndromes such as progressive supranuclear palsy and multiple system atrophy.
"They're actually using what we found!" Lazzarini said. "To me, that's bigger than finding the gene in the sense it's more immediate for patients."
The August release of "Both Sides Now" also coincided with a new American Parkinson Disease Association public awareness campaign, which included the book. Part of the proceeds from its sale will benefit the association, which helped fund Lazzarini's research.
On Robin Williams
Finally, though there have been some public figures known to have Parkinson's, including the late Pope John Paul II, no celebrity news so shocked the public as the August suicide of comic genius Robin Williams. At 63, he had been struggling with the early stages of the disease.
"I wrote on my blog that people shouldn't be blaming his medication for what happened," Lazzarini said. "I also feel very strongly that he had a right to do what he did. He realized that his career was dependent on being sharp, quick, and witty. I respect his decision to say, 'This is not for me.'"
While Williams was reported to have been depressed, she said, that's not unusual. Often, Parkinson's and depression go hand in hand.
"What he did is a matter of control. It's a decision and a valid one," Lazzarini offered. "He saved his family from the burden of his illness. To respect his autonomy to do that is very important."
After her diagnosis, Lazzarini changed her life. Even though she realizes the extensiveness of the help she'll one day need as her Parkinson's progresses, she ended her 43-year marriage and now lives, alone and emotionally free.
Facing Parkinson's
"How do I face Parkinson's? I try to get the most out of each and every experience," she said. "No one has any guarantees in life, so it's a matter of playing your cards as well as you can.
"Quite honestly, I'm relieved I don't have Parkinson-plus," she added. "I'm relieved I have tremor-predominant. From time to time, I'll send an email I didn't mean to send because of tremor. I laugh about it, cry about it, and live with it."
Typically, her form of Parkinson's is a 20-year disease.
"But I want 21, at least," she said, "so we'll see."
Parkinson's disease affects one million people in North America and more than 4 million worldwide, according to the U.S. National Library of Medicince. About 60,000 new cases are diagnosed each year.
Lorraine Ash: 973-428-6660; lash@njpressmedia.com
Learn more
Catch up with Alice Lazzarini, author of "Both Sides Now":
•"Parkinson's Blog," www.alicelazzarini.com
•"Neurogenetic Journey," Psychology Today blog, www.psychologytoday.com/blog/neurogenetic-journey/201412/join-me-journey-discovery
•American Parkinson Disease Association website, www.apdaparkinson.org
•On Facebook, www.facebook.com/pages/Dr-Alice-Lazzarini/572804469481165
•On Twitter, @lazzaral
•On wikipedia, http://en.wikipedia.org/wiki/Alice_Lazzarini
In person, at these upcoming readings/discussion:
•TBA January, College of St. Elizabeth, 2 Convent Road, Convent Station, info at lazzaral41@verizon.net
•2 p.m. Feb. 10, CareOne at Hanover Township, 101 Whippany Road, Whippany, info at lazzaral41@verizon.net
•1 p.m. Feb. 16, CareOne at Morris Assisted Living, 200 Mazdabrook Road, Parsippany, info at lazzaral41@verizon.net