“My mother had always been haunted by Parkinson’s because her aunt had suffered from it,” Sergey Brin, one of the two Jewish co-founders of Google, wrote in a 2008 blog post. “For more than 20 years, my mother has worked with computers at NASA. So, when she developed pain in her hands, the diagnosis seemed easy: repetitive stress injury. It was only after visits to many specialists over a number of years that the diagnosis settled—Parkinson’s disease.”
After learning that his mother had Parkinson’s disease, Brin visited his account at the website of the genetic-testing company 23andMe, founded by his then-wife, Anne Wojcicki. There, he was surprised to discover that he carried a LRRK2 (or “Lark two”) mutation, one that is known to cause his mother’s condition.
Brin is hardly alone among Ashkenazi Jews. The Israeli writer Naomi Levine, an ultra-Orthodox Jew, had a sister diagnosed with Parkinson’s. “She knew she had the LRRK2 mutation,” said Levine. “And she asked me to do a favor for her with genetic testing. And of course, I told her I would. And my husband also did the testing because his father had Parkinson’s. When I realized I also carried it and that I could get Parkinson’s, all I thought was, ‘There goes the bell of doom.’”
April 2017 marks the 200-year anniversary of James Parkinson’s “An Essay on the Shaking Palsy,” in which he formally etched observations of his now-eponymous disease. We now know that two genetic mutations, LRRK2 and GBA (also linked to Gaucher disease), are more commonly found within Ashkenazi Jewry, said Roy Alcalay, a Columbia University neurologist, who has led several efforts to clinically characterize Parkinson’s disease within Ashkenazi Jews. An Ashkenazi Jew with Parkinson’s has a one in three chance or greater of carrying a mutation in LRRK2, GBA, or both. These mutations are in no way specifically or even heavily Jewish—North African Arab-Berbers with Parkinson’s, for example, are also affected by the LRRK2 mutation—but 1 percent of Ashkenazim carry LRRK2 and up to 9 percent carry GBA. Which means that, if nothing else, we Jews ought to be paying attention.
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Since James Parkinson’s day, there has been increasing recognition that Parkinson’s disease comprises a cluster of different diseases, said Alberto Espay, neurologist and endowed chair at the University of Cincinnati. No two cases are identical. Neither Brin’s mother nor Levine, for example, have tremors. And while tremors are often seen as Parkinson’s hallmark feature, they are in fact less common in certain patients with an LRRK2 mutation, who may have other symptoms, like slowness of movement, stiffness, and gait problems, that support the diagnosis.
Therapies currently approved by the FDA focus on treating the symptoms, but are in no way tailored to the varieties of Parkinson’s. “As a scientific community, our goal is to determine what makes different types of Parkinson’s disease different from one another,” Espay said. This approach will help personalize drugs that might cure a type of Parkinson’s, depending on a combination of genetic and clinical information.
Ziv Gan-Or, of the Montreal Neurological Institute, who has spearheaded studies on the genetics of Parkinson’s, especially GBA within Ashkenazim, points out that for most people, their lifetime risk falls between 1 percent and 2 percent. But for LRRK2 carriers, there is a 30 percent chance that they will develop the disease in their lives. And certain GBA mutations increase risk roughly to between 3 percent and 6 percent—while other GBA mutations may increase the risk 40-fold.
Given the evolving information, genetic counseling and testing may be important. “The first step is genetic counseling, is to provide the information we currently have on GBA and LRRK2,” Alcalay said. “The second step is to see if the person receiving the counseling would want to get genetic testing. Many of our patients choose not to get genetic testing, but some do. It’s a very personal decision.” Feeling an obligation to help her sister in any manner possible, Levine, for example, immediately enrolled in an LRRK2 study after learning of her sister’s results.
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Most patients do not arrive at a movement-disorders neurologist with a family history or with results from genetic testing. For bariatric surgeon Lou Flancbaum, his first sign—in retrospect—was several years with diminished sense of smell. “I never exercised, and I just bent over and operated on people’s abdomens,” Flancbaum said. “I was in lousy physical shape. I had a lot of stress.” At age 53, he noticed that his right arm barely swung while walking. And a tremor at rest had appeared in his hand.
Flancbaum also noted that even prior to his loss of smell, his speech was often difficult to understand. “It went from bad to worse,” he recalled. “When I was a medical student in 1978, someone nicknamed me ‘Mumbles.’ And I don’t think I had Parkinson’s back then.”
In May 2007, Flancbaum and his wife visited a movement-disorders neurologist. It was there that he received news that Parkinson’s would force him to retire from the operating room. At later appointments, Flancbaum would undergo genetic testing. No known genetic factors, however, were identified. Research into the causes of Parkinson’s is a vibrant area of exploration, said Gan-Or, with many genes, such as GBA, pointing to problems with cellular degradation.
In 2012, a few years after her enrollment in the study, Levine noticed that her walking became slower. People rushed past her. A visit to the Western Wall that usually took 40 minutes now took over two hours. And she started to trail behind her husband when walking. Yet neurologists assured her that she didn’t have Parkinson’s.
But she continued to fall. Her frustration intensified. She visited her doctor—again. She was referred to another neurologist, who did a brain scan to examine her level of dopamine. Levine vividly recalled the experience. “The neurologist, before seeing the results, said, ‘You don’t have Parkinson’s.’ But then he looked at the results of my scans. And he said, ‘I’m afraid you have Parkinson’s disease.’”
Once diagnosed, Levine read everything she could. But Parkinson’s is so stigmatized among her fellow Haredi Jews that she forgoes the use of the word disease altogether. “Parkinson’s is very isolating, and is usually viewed as a death sentence in this Haredi community,” Levine said. “Some people would prefer to receive a diagnosis of late-stage cancer. Rabbis in the community are anxious to change that—and they know this is wrong. Because of the stigma, these patients remain at home and quickly turn into invalids.”
Along with her friends, she is trying to reverse the tide through her backing of nascent support groups, such as Tikvah for Parkinson’s (author’s note: I am an ad hoc consultant for Tikvah for Parkinson’s), that strive to educate families about the prognosis of the disease, what studies are ongoing for mutation carriers, and provide activities that promote exercise and psychological well-being.
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Now retired from surgery, Flancbaum, together with his wife, assists people in finding neurologists in New York. He keeps up an exercise regimen of Krav Maga, yoga, golf, and boxing. “I think a lot of people are coming to grips,” Flancbaum said. “Maybe I don’t have a hard time because I am doctor. And if people know what I have, then they know what I have. It’s not a secret.”
Levine is optimistic about the future. “My feeling is that something will come out in the next few years,” she said. “That makes me hopeful and not fearful for my children who may also carry this genetic mutation.”
Alcalay said that drugs of the future may slow the disease in gene-carriers—a potential silver lining for patients with genetic forms of Parkinson’s. Within the next few years, he envisioned, such agents will be tested—and he hopes that they will work. Gan-Or highlighted ongoing clinical trials throughout the world. “That’s one achievement—partly because of our research,” he said. “Match treatments that will target genes or specific pathways by our genetic studies.”
Flancbaum, who has surprised his doctors by his slow progression, remarked that he has yet to have a Parkinson’s-related fall. And he repeatedly emphasized that most people die with the disease, not from it.
“It’s not a death sentence,” Levine concluded. “But you do have to live your life differently—and prioritize and be very proactive. And if you don’t take care of yourself, no one else will. Learn everything you can, and connect with people.”