LOTS of living left

Twenty years ago, when she was 14, Vera Pesotchinsky’s speech became slurred at times, so her parents sent her to a speech therapist. Later, she began to have coordination problems and occasionally fell. She never could peel potatoes.

“I told physicians, ‘Something isn’t normal,'” says her mother, Sophia Pesotchinsky, who lives in Los Altos. “Something is going on, especially [with her] speech. They sent to her to a psychiatrist. She also saw a neurologist.

“Nobody recognized the problem.”

Twelve years later, after many misdiagnoses, the Pesotchinskys got the news: Vera has Late-Onset Tay-Sachs (LOTS), an incurable and virtually untreatable disease.

“I just thought I was a klutz,” Vera says. “I had no idea it was medical.”

Unlike the fatal infantile variety of Tay-Sachs, LOTS is not necessarily life-threatening, but it is progressive and can be relentless. About 30 percent of those with the condition have psychiatric symptoms.

Many, such as Julie Stein of Woodland Hills and Eric Pastor of Encino, are unable to work or live alone. Stein, 43, a former union carpenter, now uses a wheelchair and lives with her mother and her service dog, Jamie. Pastor, 33, can’t find employment because his speech is difficult to understand. He can no longer drive and has problems handling a computer keyboard. His mother, Bonnie, gave up her job in real estate to care for him.

“Vera is one of the lucky ones,” says her mother. She works. She drives. She exercises. She has a full social life.

“I live alone. I cook. I clean. I do all the normal things,” Vera says.

However, keeping her balance — especially on stairs — is a major concern. Short of a miracle, Vera, like many others with LOTS, may eventually need a wheelchair. But that miracle may be on the horizon, thanks to remarkable results in animal studies being conducted by a consortium of scientists that presage hope for gene therapy among Tay-Sachs patients. The plan is to implement clinical trials among humans within three years.

If gene therapy proves successful with Tay-Sachs, researchers say it could help those afflicted with other genetic disorders, including Gaucher’s, Canavan and Niemann-Pick diseases, which also are most common among Ashkenazi Jews.

“There’s a possibility for a cure,” says Sophia, who chairs the oversight committee of the newly formed Tay-Sachs Gene Therapy Consortium, building contacts with physicians and scientists in England and the United States who are working to find a cure. “I feel we will win.”

With a professional background in medical research and biomedical engineering, Sophia brings a scientific perspective to her primary goal: raising funds to support the research. A board member of the Jewish Community Relations Council, she recently established a Tay-Sachs research fund under the aegis of the Jewish Community Endowment Fund in San Francisco. She is hoping to raise $500,000.

“We’re both fighters,” Sophia emphasizes. “I have to fight to find a cure. She has to exercise.”

While Sophia discusses the research, Vera sits against the wall of her bedroom practicing Dahn yoga to build strength and alleviate stress. An exercise bicycle sits in her bedroom, and books on healing and meditation fill the shelves of her study. Three times a week, she exercises with a personal trainer, and she recently attended a yoga retreat.

She has a cane she has never used, because her parents felt she should have one. To appease her parents, she also ordered a disability placard for her car.

“I need to walk,” says Vera, who is slender, curly-haired and describes herself as “happy and optimistic.”

She is adamant about not becoming “a Tay-Sachs poster child.” A Wellesley graduate with an MBA from Santa Clara University, Vera works five or six hours a day in her family businesses, the Silicon Valley-based LSVP International, a medical device business, and the eponymous Hotel Vera in St. Petersburg, Russia, her birthplace. In Russia, Sophia notes, screening for genetic disorders is not common.

Five years ago, it was reported that the illness — a rare genetic disorder primarily associated with infants of Ashkenazi Jewish background — had been virtually eradicated among Jews because of prenatal or premarital genetic screening, which began in 1970.

Nevertheless, about 50 to 75 American children — some Jewish, most not — are living with the disease, according to the National Tay-Sachs and Allied Diseases Association. In addition, about 100 living American adults have been diagnosed with LOTS. The majority are Jewish, but some are of French Canadian, Cajun and Irish backgrounds.

Because the illness is so rare, most adults with LOTS have been misdiagnosed for years, according to Sophia. Many physicians are unaware of it. “That’s one of the scary parts about this. We have no idea how many cases are out there,” says Bonnie Pastor in a phone interview. “It’s not something doctors know about, even neurologists, and it’s not something they test for.”

For the Pesotchinskys, getting a diagnosis was a relief. The neurological, kinesthetic and phonic symptoms were “all tied together,” says Vera, who immigrated to the United States with her parents in 1976, landing in California with $300 in their pockets.

“We were really political refugees,” says Sophia, noting that they were among the first wave of émigrés. Fortunately, her husband, Leon, a statistician, was able to get a university position. Now he and Sophia are in business together.

Through her outreach, Sophia keeps in touch with others coping with LOTS, including the Pastors. Eric Pastor wrote about his condition recently in the Los Angeles Jewish Journal.

“Finding or keeping employment has been very difficult,” he wrote, noting that since adulthood, the disease has “taken a greater toll on my body.”

It has also taken a toll on his spirit.

“I have lost employment because of my slurred speech and feel discriminated against each and every time I go into an interview.”

About a dozen years ago, during a difficult third pregnancy, Bonnie Pastor discovered she was carrying a Tay-Sachs baby; doctors advised her to abort. Then she decided to have her two grown children tested. Perhaps, she wondered, they might be carriers.

When she found out Eric had Tay-Sachs, “I almost fainted,” she says. “This was the same doctor who said to me, ‘You’ve got to be thankful you have two healthy children.'” (Eric’s older sister is not a carrier.)

Later, Bonnie put an ad in the Jewish Journal announcing, “Did you know Tay-Sachs is not only an infantile disease?” She listed the symptoms and began to get calls.

“I’ve talked to so many people, they go for years not knowing, and I’m sure I would be one of those,” she says.

Julie Stein, who also lives in Southern California, says she was the 83rd documented LOTS case in the world. When she was diagnosed in 1997, she was working as a union carpenter. But suddenly she couldn’t pull herself up by her legs and needed to use her hands to give herself a boost, forcing her to hang nail pouches from a shoulder strap. When she went dancing, she began to have equilibrium problems.

Stein continued working until 2000, when she went on Medicare and Medi-Cal. Two years ago, she fell, crushing her big toe badly, so she now needs to use a wheelchair.

After Stein was diagnosed, her two sisters got tested. One is a carrier. The other is much more seriously afflicted than her and has severe speech difficulties.

Stein helped with the logistics for the 20th annual national Tay-Sachs family conference, which took place late last month in Tampa, Fla., making sure wheelchairs were available for those who needed them. About nine adults with LOTS reportedly attended, most Jewish or French Canadian.

Just before the conference, Stein was looking forward to hearing the speakers and the opportunity to meet other adults and families who are coping with the illness. On the other hand, “It’s sad, because we see the babies who end up passing away.”

Meanwhile, her mother, a widow, has been battling cancer. “I help her, she helps me,” Stein says. “I just keep going. I’m a fighter.

The Pesotchinsky family also maintains a positive attitude.

“You can fall apart and be a wreck or do what you can with it,” says Vera. “If I didn’t do what I do, I’d get worse.”

Sophia also attended the Tampa conference, meeting with scientists. Her mission to find and fund a cure remains a driving force.

“It’s probably my destiny. It’s something I have to do,” she says. “After this particular disease, I want to use this as a platform to find a cure for other diseases. I’m not going to stop until we find a cure.”

What is Tay-Sachs? The bottom line

Tay-Sachs is an incurable genetic disorder resulting in the deterioration of the central nervous system and leading to progressive loss of motor skills. It is caused by the absence or near-absence of a critical enzyme known as hexosaminidase A.

In the classic infantile variety, death generally occurs before age 5. In both juvenile and adult or Late-Onset Tay Sachs (LOTS), a small amount of Hex A is present, delaying the onset and progression of symptoms.

While few with juvenile Tay-Sachs live beyond their 20s, the illness among adults is not necessarily fatal. However, the illness is progressive and incurable, and about one-third of adults with LOTS may experience psychiatric disorders. Many are in wheelchairs.

Who is affected?

About one out of 25 to 30 Ashkenazi Jews carries the recessive gene. In addition, French Canadian, Cajun and Irish families may also carry the gene.

If two carriers have children, the odds are that one in four of their children will have Tay-Sachs, one in four will not carry the gene and the other 50 percent will be unaffected carriers. If a carrier marries a noncarrier, none of their children will have the illness, but 50 percent will be carriers.

How to prevent Tay-Sachs

Since the advent of premarital and prenatal genetic screening in 1970, as well as amniocentesis, the number of Tay-Sachs births has dropped from about 100 annually to about a dozen.

Most couples who discover they are carrying an affected fetus choose to abort. In some Orthodox communities, teens undergo screening, and couples may be discouraged from marrying or dating if both are carriers. However, while Ashkenazi Jews undergo screening, others may be unaware that they are at risk.

Why does gene therapy look promising?

In 2007, scientists in Britain and the United States formed the Tay-Sachs Gene Therapy Consortium with the goal of launching human clinical trials in three years. The consortium is receiving assistance from the Genzyme Corp., which has developed enzyme replacement treatment for Gaucher’s and Fabry’s diseases, both genetic disorders.

The belief is that gene therapy, which has already proven successful for mice and cats, has the potential to cure Tay-Sachs or slow its progress, and possibly treat other disorders, genetic and otherwise. Affected mice that would normally die at 17 lived for at least a year after direct injections into the brain. (For comparison videos, go to www.tsgtconsortium.com and click on “Animal Studies.”)

Consortium member Dr. Timothy Cox, professor of medicine at the University of Cambridge, writes in an email to j., “The correction of inherited disorders by gene therapy was much talked about 20 years ago: the promise was great but the results dismal. Now the tables have turned.

“In many ways Tay-Sachs disease is iconic in the hard world in which patients with rare (orphan) diseases live,” he adds. “It is [in its] early days yet, but we know that our success will serve as a generally applicable model for neurodegenerative processes in other more familiar disorders such as Alzheimer’s disease, in which the genetic component is usually less clear. We recognize that the success of this consortium will have far-reaching consequences; it will also bring benefits to medical research way beyond its own limits.”

Resources

National Tay Sachs and Allied Diseases Organization (www.ntsad.org)

Tay-Sachs Gene Therapy Consortium (www.tsgtconsortium.com)

Chicago Center for Jewish Genetic Diseases (www.jewishgeneticscenter.org)

Center for Jewish Genetic Diseases at Mount Sinai Medical Center (www.mssm.edu/jewish_genetics/diseases/tay-sachs.shtml)

How to contribute

Send tax-deductible contributions to the Jewish Community Endowment Fund, Attn: Phyllis Cook, 121 Steuart St., San Francisco, CA 94105. On the memo line of your check, write: Tay-Sachs #797.

Janet Silver Ghent

Janet Silver Ghent is a writer and editor living in Palo Alto. She can be reached at ghentwriter@gmail.com.