To be considered for the clinical study on the new drug Ataluren, originally called PTC124, CF patients “must know their genetic mutation,” said Teaneck resident Dr. Jay Barth, executive director of clinical development at PTC Therapeutics, Inc., the South Plainfield-based company that is beginning Phase III trials for the new drug. Barth, a Teaneck resident, explained that “many patients already know their mutation. If not, they have to have genetic testing.” Patients who carry at least one copy of a nonsense mutation (see below) may qualify. Also, patients must be at least six years of age, and have lung functioning within a certain range.

Cystic fibrosis can be caused by many different forms of mutations in the CFTR gene. The CFTR gene makes a protein that normally handles the movement of salt across membranes and the secretion of fluids and mucous. Since fluid management and mucous play important roles in many critical organs, CF can affect the lungs, liver, pancreas, reproductive structures, and sweat glands.

In the cells, genetic instructions normally direct the ribosomes — cellular protein factories — how to assemble proteins. Some mutations change genes so that a dysfunctional protein is made. Nonsense mutations are stop signals that are located in the middle of a gene; they cause the production of protein to be interrupted prematurely, so a shortened protein is made. Ataluren is a chemical that can help ribosomes ignore the stop signal and complete the protein. When the normal protein is made, normal functioning throughout the body can be restored. If this approach works, Ataluren could essentially cure the disease in patients with the nonsense mutation.

Dr. Jay Barth

“About 10 percent of CF mutations are due to nonsense mutations,” said Barth. However, within Ashkenazi Jewish CF patients, up to 60 percent of mutations are nonsense mutations.

A three-month Phase II study, led by Drs. Eitan Kerem and Michael Wilschanski and their colleagues, was conducted at Hadassah Medical Center in 2008. The results of the study, published in The Lancet, suggested that many patients had improved salt transport in their tissues. “Hadassah was always a leader in CF research, in particular because of the high percentage of nonsense mutations in the population there,” said Barth. “They are one of the sites in the Phase III study.”

“There are numerous sites in the U.S., Europe, and Israel that are actively recruiting for the Phase III study,” said Barth. Children’s Hospital in Pittsburgh is taking applications and Saint Vincent’s Hospital in Manhattan is planning to participate, although it has not started recruitment yet. Other sites are planned for Westchester and New Jersey, but they have not been finalized.

During the trial, patients will take the drug three times a day in powder form, mixed with water, juice, or milk. The drug is absorbed through the digestive system, enters the blood stream, and goes everywhere in the body, targeting the production of protein by ribosomes affected by nonsense mutations.

The double-blind randomized trial will involve dividing the patients into two groups — one of which will receive the drug and the other a placebo for 48 weeks. Barth explained that after the initial study there will be an “open label extension study where all patients who choose to may continue for another year on the drug.” If proven to be effective in correcting cystic fibrosis due to nonsense mutation, the drug would have to be taken for the rest of the patient’s life. Research has shown that the drug is generally well tolerated with few side effects and very high patient compliance (up to 99 percent of patients continue to take it).

Barth explained that numerous other diseases are caused by nonsense mutations in other genes, and they might also be helped by Ataluren. There have been clinical trials of Ataluren for Duchenne muscular dystrophy caused by nonsense mutations, and there are also studies under way for hemophilia caused by nonsense mutations. Barth said that an estimated 15 percent of all patients with 7,000 rare genetic disorders have nonsense mutations, and many of those patients could be helped by this novel therapeutic drug.

“This gives hope of treating a disease that, until now, there has been nothing to treat the underlying cause,” said Barth. He noted that there are other types of drugs being developed that may be useful for other types of mutations. “Science is advancing and hopefully there will be several different treatments for CF,” Barth said.

Information on PTC Therapeutics and Ataluren clinical trials can be found at http://www.ptcbio.com. For more information, call Diane Goetz, patient advocate, at (866) 282-5873. Information on clinical trials can be found at www.clinicaltrials.gov.

The recent film “Extraordinary Measures” tells the real-life tale of a family with two children who are suffering from a fatal genetic disorder. Their father takes drastic steps to encourage and support the work of a brilliant scientist, whose insight leads to a miracle drug that saves the lives of the children. The CF story may have a similar path to a happy ending — with the work of some extraordinary Israeli physicians and researchers leading to a new approach to cure CF.

The CFTR protein is the source of all problems in cystic fibrosis. CFTR stands for cystic fibrosis transmembrane conductance regulator. Its normal function is to move salts across cell membranes throughout the body — a process that is essential to the proper functioning of the lungs, kidneys, pancreas, and other organs, as well as the normal growth and development of the vas deferens, a structure that transports sperm in men.

Israeli scientist and physician Eitan Kerem has spent more than two decades studying CFTR and cystic fibrosis from a genetic as well as a clinical perspective. Dr. Kerem’s research, in collaboration with many other Israeli researchers as well as other scientists worldwide, has helped reveal the genetic underpinnings of CF, as well as the most effective ways to treat patients and alleviate symptoms of the lethal disease.

Dr. Eitan Kerem

Kerem’s research career started in the early 1980s, with his first CF papers appearing in 1989. At that point, he and his colleagues were already intrigued by the genetic and clinical aspects of CF. He began to publish studies of specific mutations 20 years ago, with the identification of Delta F508 as a major mutation in the Ashkenazi Jewish community. Kerem co-authored a paper in 1992 on W1282X, a nonsense mutation in the Ashkenazi Jewish population. This was an early exploration into the possibility of treating different mutations using different approaches.

Kerem, along with colleagues at Shaare Zedek Medical Center, and later at Hadassah Medical Center, also pursued various approaches to treating the lung infections and other complications in CF patients. His publication list includes a 1992 paper on “Undescended testis and absence of vas deferens,” describing male infertility issues of CF, as well as an intriguing article, written in Hebrew, on “CF as a model of ethical issues: Abortion of fetuses carrying a disease with survival to adulthood.” He was also involved with research on “nasal potential difference measurements,” a measure of secretions in the nose; that research has led to a reliable test to diagnose CF.

Kerem was named director of Pediatric Pulmonary Medicine at Shaare Zedek Hospital in 1996. In the 1990s, he and his co-workers published numerous articles on a variety of mutations associated with CF. In 2000, Kerem was co-author of a paper that described the use of the antibiotic gentamicin to bypass a nonsense mutation, and restore normal gene activity. Gentamicin turned out to be toxic in concentrations needed to overcome the mutation. Although it was not practical for treatment of CF patients, the gentamicin research led to the development of other pharmaceuticals that could accomplish the same goal — the restoration of normal protein production in patients with nonsense mutations — with much lower risks of toxicity.

In 2002 Kerem was appointed head of the Department of Pediatrics at Hadassah Medical Center, where he founded the Center for Chronic Diseases in Children. He and his colleagues published a landmark paper in 2005 in the renowned British journal The Lancet, reporting on the “induction of CFTR function in patients with cystic fibrosis: Mutation-specific therapy.” This report suggested that genetic mutations could be treated and overcome with drug therapy. The Lancet published an account of the Phase II clinical trials of PTC124, now known as Ataluren, in a paper authored by 14 researchers, including senior authors Kerem and Michael Wilschanski of Hadassah Hebrew University Hospital in Jerusalem, scientists from PTC Therapeutics in South Plainfield, N.J., as well as researchers from the Hebrew University Department of Genetics and three other Israeli hospitals. That paper serves as one of the cornerstones in the research for an effective drug to help CF patients overcome the basic genetic defect of the disease.

Kerem is by no means a one-man show; many of his publications include names of scientists that he has collaborated with many times in the past 20 years, including his wife, Dr. Batsheva Kerem. But his remarkable record of more than 140 published papers is testimony to a life dedicated to curing this very challenging disease. The state of the research now appears to be highly promising and may prove to have generated a long-awaited drug that will extend the lives, and improve the quality of life, of many CF patients.

Hadassah Hebrew University Hospital now has a Cystic Fibrosis Center at the Mount Scopus campus in Jerusalem that offers services for patients with cystic fibrosis. Kerem is its director. The multidisciplinary approach includes pediatric and adult medical care by specialists such as pulmonologists and gastroenterologists, as well as nutritional counseling, psychological services, and support groups for families. It provides screening and genetic testing services and physiotherapy, and its research faculty and staff continue to pursue studies to improve the quality of life of CF patients, as well as to identify and address the basis of the disease.

“We started the phase III Ataluren study in Hadassah three months ago, and enrolled, so far, close to 20 patients,” reports Kerem.

Information on the CF Center at Hadassah can be found at http://www.hadassah.org.il/English.

Sarah and Jeffrey Yourman don’t let their disease keep them from an active life.

Lisa and Steven Yourman and their two teenage children have all the trappings of the typical suburban Jewish family. A ketubah (Jewish marriage contract) and family portraits are displayed prominently on the wall of their split level home, their cat roams around the books, electronics, and other possessions of a busy family life, and a basketball hoop and four cars occupy their driveway. But their Fair Lawn home also has signs of their remarkable challenge: the medical equipment and cartons of medical supplies necessary to care for Sarah and Jeffrey, both of whom have cystic fibrosis.

Cystic fibrosis (CF) is a genetic disease affecting about 30,000 people in the United States. It is more prevalent in Caucasians. The incidence among Ashkenazi Jews is similar to that for Tay-Sachs: About one in 29 Ashkenazi Jews is a carrier. Carriers have no symptoms, but when two carriers have a child there is a one in four chance that the child will have CF.

CF is a lifelong illness with no cure. It affects many critical organs, including the lungs, liver, and pancreas. Just a few decades ago a CF patient’s life expectancy was in the teens, but now, because of antibiotics and other advances in treatment of symptoms, many CF patients live active lives into their 50s.

Lisa and Steven Yourman have hope that the prognosis for their two children will be even better, as a new drug that treats the underlying defect is being tested and may soon become available. Over the years there have been many potential therapies offering hope that did not pan out, but the new drug, Ataluren, works in an entirely different way, explained Lisa Yourman. “There were other drugs I never got excited about. There was an IV [intravenous] medication that, when given in very high doses, corrected the defect, but there were serious adverse reactions. But this one is different. The drug is 11 years in the making,” she said.

“Everyone carries two copies of the gene for the sodium channel protein. The two versions could be the same or different,” said Yourman. The Yourman children have among the most common mutations: Delta F508 and G542X. It is the G542X mutation that gives them hope, as it is a so-called “nonsense mutation.” Normal genes provide instructions to guide the production of all the proteins that control the functions of the body. When a nonsense mutation occurs, the mutated gene contains an error that blocks the production of a complete protein. A CF nonsense mutation is an error in the genetic instructions that interrupts production of a key protein needed for transport in many organs. The partial protein that is made does not work properly and leads to serious complications in mucous secretion and production of other fluids. The new drug Ataluren may be able to reverse the defect caused by a nonsense mutation such as G542X mutation (see sidebar).

“The drug has been extensively tested at Hadassah Hospital in Israel,” said Yourman. “The drug is in clinical trials. Now it is being tested around the world.” Lisa recalled her late mother-in-law, Janet Yourman, who was very active in Fair Lawn’s Hadassah chapter, raising money for Hadassah Hospital for almost 50 years. Lisa believes that work of Janet Yourman and others like her on behalf of Hadassah may have helped lead to the development of this drug.

The Yourmans will be applying for Sarah and Jeffrey to participate in Phase III trials at Children’s Hospital in Pittsburgh, where trials are scheduled to begin shortly. It is a 48-week double-blind randomized trial, which means that half the patients get the treatment and half a placebo, an inert medication. “The worst that can happen is that you can waste a year,” said Lisa, referring to the possibility that her children might be assigned to the placebo group. After the trial, the patients who received the placebo are eligible to take the drug.

“We are so excited. I hope they both qualify,” she said.

Life in a CF family

Lisa Yourman demonstrates the preparation of antibiotics for Sarah’s IV. MIRYAM WAHRMAN

For Lisa Yourman, taking care of two children with CF involved learning how to administer medications, advocate for medical services, negotiate complex health insurance issues, and schedule daily therapy sessions, all while providing opportunities for Sarah and Jeffrey to have normal childhood activities. The treatments for CF symptoms have improved dramatically, allowing the children to live remarkably normal lives despite the fact that the regimen needed to maintain their health is daunting. Yourman works as an advocate to help other parents deal with CF and has even lobbied in Trenton on health-care issues.

Yourman brims with pride over her children’s accomplishments. “I have two kids with chronic disease with them every single day of their lives, and they are very successful academically,” she said.

Sarah, 19, is a sophomore at Kean University. The petite and perky teen is studying for a bachelor of fine arts degree in theater design and technology and would like to work in theater lighting design. Sarah also suffers from CF-induced diabetes and she has done public speaking as a diabetes advocate. She was on the cover of “Diabetes Positive” and received the Michael Brennan courage award in 2009 from the CF community.

When she is at college, Sarah gets up two hours before class to perform her treatments, which involve using a mechanical vest that dislodges the mucous in her lungs. Before bed she takes a handful of pills, including antibiotics and medications to thin the mucous.

“I’m not afraid to share that I have CF and diabetes,” said Sarah. “There are four of us students who are really close and work together [on projects]. There is an 8-foot ladder to reach the equipment in their 12-foot ceilings. It’s dubbed the Sarah Yourman ladder,” she said with a smile. “When I first got there I would not get on the ladder, but I got over the fear of ladders. We also have a cherry picker in the department, for the main theater, and I went up in it,” she said.

Growing up, Sarah was a competitive free-style skier, a sport that involves jumps and aerial stunts. Now she focuses on downhill skiing and has recently taken up snowboarding. Throughout the winter, Sarah and her father work as ski coaches at Wyndham Ski Resort. “I usually go skiing every weekend from December until mid-March,” she said. “This year I have so much going on that I just go whenever I can.”

Jeffrey Yourman demonstrates the mechanical vest. MIRYAM WAHRMAN

She still laments the season she missed when she was 16 and had scoliosis surgery. “I have two titanium rods and 16 screws in my back,” she said, adding with a smile that this coincides with her birthday, which is Feb. 16 (2/16).

When Sarah is home, she gets chest physical therapy, which Jeffrey still gets 365 days a year. “The kids get beaten on every day,” said their mother. A physical therapist drums the chest and back with cupped hands to dislodge excess mucous and relieve breathing. The treatment, which may be needed several times a day, lasts about 45 minutes. For Sarah, being home also frequently involves intravenous antibiotic treatment to counteract infections she may have picked up at school.

Since many CF children have growth issues, both Sarah and Jeffrey were prescribed growth hormone. “Jeffrey, who started at an earlier age, is still on it,” said Yourman. “His predicted height was 5 feet, and he is now 5 feet 7 1/2 inches.”

Jeffrey and Sarah have both participated in camps and trips sponsored by Chai Lifeline, Camp Simcha, and a new organization called Kids of Courage. Those organizations provide mechanisms for Jewish children with serious medical needs to enjoy camping and travel experiences. “In March 2009 Jeffrey took a fully paid trip to L.A,” said Yourman. “The camp takes care of medicine, therapy, etc. They are phenomenal in every way in dealing with medical issues.”

Although Jeffrey’s approach to dealing with CF is “don’t think about it,” he displayed remarkable patience and willingness to discuss his experiences. A sophomore in high school who just turned 17, Jeffrey is excited about getting his driver’s license. He loves to play basketball and is a Lakers fan. For Jeffrey, the Make-A-Wish Foundation sponsored their family for a Hawaiian cruise last year. His favorite part of the trip was driving a dune buggy.

The Yourman children do not have activities together with other CF teens. “Because of cross-infection, CF kids are not allowed to hang around together,” said Yourman. “Jeffrey doesn’t have much contact with other kids who have CF since it presents a risk that they will transmit infections to each other.”

“Whatever your kids want to do, don’t say no,” Yourman advised. “The only time our doctor said ‘no’ was when Sarah wanted to go to EMT school and volunteer on the ambulance,” because of the risk that she would be exposed to infections.

“A normal life is whatever life you lead that brings satisfaction to you and inspiration to others,” Sarah said. “I lived it all my life, so I don’t know how to live it any other way.”

Information on the clinical trials for Ataluren can be found at www.ptcbio.com. Information on CF can be found at the Website of the Cystic Fibrosis Foundation, www.cff.org

Above, members of the caregivers group are pictured in front of jigsaw puzzle art they completed. Seated from left are Jacqueline Staudt, Lee Kelly, Joyce Zaccardo, and Jerry Lieberman; standing from left are Elaine Adler and Sheila Dempsey. Miryam Wahrman

Mary Slade, a panelist at an Adler Aphasia Center information session who is recovering from aphasia, observed, “It takes a family time to accept that a person had a stroke and has aphasia. When you first get sick there is often anger, confusion, and frustration.”

Elaine Adler became a caregiver when her husband Mike had a stroke. “When the breadwinner becomes aphasic, what happens to the family?” Adler asked. “The spouse has to take care of the aphasic and the family…. I realized how important it is to help the caregiver.”

The center has a support group for caregivers, run by Sheila Dempsey, a life coach. Caregivers in the group reported that they typically drop their spouses off for programs and then go out for breakfast together. Then they return to the center and join Dempsey for a discussion of issues related to being a caregiver.

Dempsey said that talking to others who can understand the issues and stresses of caring for an aphasia patient is very helpful. “You share things and you find out you’re not alone,” said Lee Kelly of Norwood, who cares for Jack, her husband of 51 years.

Dempsey said that a major challenge for caregivers is to understand what the person is trying to say and to keep in mind that “these are survivors, not victims. It’s a long, arduous journey.”

Kelly’s husband, Jack, has been recovering for the past 12 years. “Jack can’t speak but he can sing. It’s a different part of the brain,” she said. “Jack says 1, 1, 1, 1. A person with aphasia thinks they are saying something [meaningful]. It’s called perseveration.” Even though their speech sounds strange, “it’s important to know their intellect is not affected,” she said.

Jerry Lieberman, of Yorktown Heights, N.Y., has been married for 52 years to Jeannie, who had a stroke 12 years ago. “Jeannie taught ESL [English as a Second Language]. Her whole world was speech. She’s bilingual,” said Lieberman. “It’s important to understand that all these people are very alert.”

“Jeannie will say ‘nay, nay, nay, nay, nay,’ and I can’t figure out what she wants. It’s hard to keep your cool all the time,” he said.

Lucille Faso, of Norwood, cares for Ronald, her husband of 52 years. Her husband has “automatic speech,” which means that he says random words without intending to.

Jacqueline Staudt, of Secaucus takes care of Fred, her husband of 54 years, who was a truck driver. He used to participate in truck rodeos where he won prizes for maneuvering giant trucks.

Joyce Zaccardo, of New City, N.Y., is caretaker for George, her husband of 48 years. George worked for the United Nations, where a major part of his job was speaking. “He can’t read or write or speak, but he can sing,” she said. “He can repeat everything you say to him, but he can’t get it out on his own.”

“When they come here they feel normal,” Zaccardo said of the center. “They feel important again. They help each other.”

“I feel that I can always see some improvement. It’s not a downhill; it’s an uphill,” said Leiberman.

How to help a person with aphasia communicate

The Adler Aphasia Center offers literature to explain the disability as well as guide caretakers and others on communicating with aphasic people. Tips on communicating with aphasic people include: • Reduce background noise. • Speak slowly in a normal tone of voice. • Simplify conversation. Use short, simple sentences. Stay on one topic at a time. • Have a pen and paper handy to write down key words while you are talking. • Ask, “Am I being clear?” or “Am I talking too fast?” • Have patience. Wait, listen, maintain eye contact. • Acknowledge the speaker’s frustration. Do not pretend to understand if you don’t. • Ask “Can you say it another way?” Gestures, drawing, or writing could help. • Ask simple yes/no questions.

Using adaptive equipment and aphasia-friendly recipes, members create culinary delights in their weekly cooking group. From left to right, Dolores Donatello, John Healy, volunteer Linda Gould, and Bob Mayer. Courtesy Adler Aphasia Center

It’s hard to daven properly because I have to learn again,” said Avi Golden, who is recovering from a stroke that left him with aphasia — difficulty in communicating — as well as difficulties in using his right arm. Golden, who is an Orthodox Jew, has made great strides in his recovery over the last three years, with the help of the Adler Aphasia Center in Maywood, but he has a hard time with prayer, as the stroke left him unable to read Hebrew. On Shabbat he goes to synagogue, but he has not yet felt ready to be called up to the Torah for an aliyah. “I look and I pray,” he said. “It’s frustrating, but it’s good also.” In September he is planning to start taking classes at Lehman College in the Bronx, where he will be working with the speech clinic “to learn Hebrew again.”

Meanwhile, the 36-year-old Golden, who lives in Queens, is continuing to take classes at the Aphasia Center and is looking forward to performing in its Aug. 11 presentation of “Guys and Dolls.” “I have a very small role, a talking role,” he said.

•

The center can be a bustling, noisy place. On Monday through Thursday mornings in its Maggie’s Café, dozens of people can be found eating, socializing, and planning their daily activities. One recent morning at their “Meet and Greet,” about 40 were looking forward to their sessions on art, writing, movies, computers, law, advocacy, and drama. Although many center members suffer from communication disorders due to stroke, head trauma, accident, brain cancer, or surgery, such activities enable them to improve their communication skills in creative and interesting ways.

Golden and two other center members were panelists in a recent information session on stroke and aphasia held at the Teaneck offices of health insurance brokerage firm Singer Nelson Chalmers.

Despite a heart condition, Golden had been a very active person, working as a paramedic, and enjoying snowboarding and rock-climbing. The stroke occurred after heart valve replacement surgery. He’s been recovering ever since, and, with an optimistic smile, he says that he would like to go back to school and study to be a doctor. He reports that, remarkably, he has been able to take up snowboarding again. But he still has tremendous challenges to overcome. “Letters and numbers are so hard … very, very hard. In my head it’s perfectly normal,” said Golden. But he added, “Speech is a problem. It’s slowly getting better and better.”

The three panelists wore “Got _________?” T-shirts. This parody of the “Got milk?” dairy campaign highlights the main problem of many aphasic people — inability to enunciate their thoughts, or difficulty in doing it.

The panelists explained that aphasia happens when there is damage to parts of the brain responsible for language. This can affect speech, the understanding of spoken words, and reading and writing abilities. “It affects a person’s ability to communicate, but does not affect their intellect,” an information card from the Adler Center explains.

Panelist Mary Slade of Hackensack, who worked for Citigroup, describes her pre-stroke self as a “multi-tasker.” After her stroke, her life changed in significant ways and she had to adapt. “I knew what I wanted to say, but it didn’t come out. You want to say ‘right’ and you say ‘left’…. It’s difficult not being able to go to a doctor and say ‘fix it.’”

Over time, she made a dramatic recovery. “Now some days are so good I forget that I have aphasia,” she said. “It does get better. Attitude, attitude, attitude makes you well or makes you sick.”

Walter Nolting, an 82-year-old Dumont resident and former postal worker, explained how, ironically, he stuttered badly almost his whole life, until his stroke in 2005. “Now I don’t stutter anymore, but it’s hard to get [words] out. I know what I want to say but can’t say it.”

“Aphasia affects each person differently. Some people can read or write but can’t speak much. Some people can speak well and reading and writing are fragmented,” explained Nolting. “Because of the way we speak, many people incorrectly assume that we are drunk or not intelligent. I get that all the time.”

“It’s like being in a country where you don’t speak the language,” added Karen Tucker, executive director of the Adler Center. “They say yes when they mean no.”

Jessica Dionne Welsh, education and training coordinator at the center, explained that aphasia is like a file cabinet whose contents get tipped over and mixed up. “Words that are closely related get confused.” She reported that the three panelists are not working, and added that aphasia “forces people into really early retirement.”

Elaine and Myron (Mike) Adler of Franklin Lakes founded the center in 2003. It serves between 80 to 100 members whose average age is the mid-60s. Seventeen staff members and more than 50 volunteers run the center’s programs.

Elaine Adler recalled how 17 years ago her husband Mike, an active and successful businessman, became aphasic. “He had a [heart] bypass [operation] and five days later a blood clot went to the brain,” said Adler.

“When he got better we realized that we are the lucky ducks,” she said. “Many are not as fortunate as we are.” Native New Yorkers who grew up in Manhattan, Mike and Elaine Adler moved to a small house in Paramus more than 50 years ago. Elaine Adler said that their business, Myron Manufacturing, was started in a garage. The company, which sells such items as pens, mugs and key rings to help companies advertise, grew over the years and is now in a large facility in Maywood.

Mike and Elaine Adler in front of the center they founded in 2003. Jerry Szubin

The Adlers owned another building nearby that they decided to use for an aphasia treatment and research center. “Mike hired a woman to go on the Internet to find out about aphasia,” Adler said. That is how they discovered Dr. Audrey Holland, a professor at the University of Arizona in Tucson. “She sits on our board. She’s a leading aphasiologist,” Adler said. The couple also found a program in London that had prepared a manual for treating aphasia. “In London we observed the Connect Program. We learned about having group therapy,” said Adler. “Connect had a book and we adapted it for American use.” More recently they have had the manual translated into Hebrew, for use in the Adler Aphasia Center in Israel (see related story).

The Adlers have four children and nine grandchildren. “When Mike got sick, our daughter ran the business,” said Adler, who was running her own company as well — a catalogue business called “Comfortably Yours,” which sells products for aging consumers. According to its website, the products are “directed to the less active, more infirm” consumer. “When Mike got sick he used a lot of my products,” she said. Now that he has recovered, she added with a smile, “I send him to work every day. I say, ‘Go make money so I can spend it.’”

The Adler Center has attracted visitors and members from many corners of the globe. “People from Aruba came to learn about the center. A speech pathologist from Italy came to learn,” said Adler. She told of an Ethiopian man who came to the Adler Center when he was told that nothing more could be done for his aphasia in Ethiopia. “My dream is that I want the word ‘aphasia’ to be at the tip of the tongue,” she said. “More than a million people [in the United States] have it, not even counting the GIs coming back [from the Persian Gulf] with traumatic brain injury. Most people still don’t know what aphasia is.”

Adler said that after traditional therapy you frequently hear the phrase “You’ve plateaued.” “It’s a word that should be stricken.” She has seen, in her own husband and in scores of members in the Adler Aphasia center, striking recoveries. “Many, after stroke, are in comas, or not able to walk or speak.” But with hard work and therapy they can make progress. “Inch by inch, it’s a cinch,” she said.

“We have the best speech pathologists in the world,” added Adler. “They are so creative.” For instance, communication coaches Karen Castka and Ginette Abbanat are directing “Guys and Dolls,” with center members playing all the roles. Adler recalled, with amusement, one of the center’s past productions. “We had more men than women [members participating], so in ‘The Sound of Music’ some of the men had to be nuns.”

“We didn’t want [the center] to be medicinal,” she stressed. The people who come there for help “are not clients. They’re not patients. They’re members.” The members come from all walks of life, and many different professions and vocations. “We have doctors, lawyers, and Indian chiefs. There’s a cardiac surgeon, a hand surgeon, a man who played the violin in the New York Philharmonic, a nurse, and a truck driver.” Another member worked for the United Nations. “His whole job was speaking,” said Adler. “Another was a rear admiral in the Coast Guard.”

Welsh, a speech language pathologist, said that classes run twice a week and members can sign up for Monday and Wednesday classes or Tuesday and Thursday classes. “Each hour we have between four and seven different offerings,” she said. Some of them, like Communication Strategies, are assigned classes, because they need to be homogeneous in terms of communication ability. “Other groups are more mixed. We make sure that everyone can participate,” she explained. “Everything is group-based except computer activities. Volunteers help members with computer projects and there is aphasia-specific software.” Welsh noted that members can become e-mail penpals with members at SCALE — the Snyder Center for Aphasia Life Enhancement in Baltimore. “The two groups Skype with each other,” she added, referring to the software used for video-chatting.

A member-run store, dubbed “Something Special,” sells products made by the members, including greeting cards, gift boxes, and calendars. Other areas are set up for art projects, photography, exercise classes, cooking, music classes, a Nintendo Wii station, and even a courtroom for mock trials. “Adler’s Court is an activity where the members reenact a courtroom drama every week,” said Welsh. “They sit on the jury and act out the whole case.”

“Our goal is to create a natural environment for people to communicate and relate to each other,” she added. “People use it as a community. For some people this becomes their life after aphasia…. It’s the life participation approach to aphasia. It helps people to re-engage in life.”

The center is also engaged in research. Holland, now a professor emerita at the University of Arizona, serves as director of research and education. She and Gretchen Szabo, the research speech pathologist, along with other administrative staff members, have presented their findings at national and international conferences. One presentation, co-authored by Szabo, Holland, and Welsh, was called “Wii-habilitation and aphasia groups: Systematic observation of communicative acts during four aphasia Wii groups.” Among their conclusions was that “[p]reliminary review suggests the use of Nintendo’s Wii Sports … provides psychosocial benefits including experiencing group camaraderie, virtually engaging in a past activity, and sharing the experience with others. It also provides opportunities to communicate reactions, celebration, disappointment, assistance, support, anticipation, competition, humor, and direct responses to other’s questions or comments.”

Members pay $18 a day to attend sessions that run from 10 a.m. until 2:15 p.m. However, the center, a 501C3 nonprofit, is mostly supported by private donations. For instance, Whole Foods donates food used in the cooking classes. One recent gift to the center was a $50,000 donation from Maggie and Bill Kaplen of Tenafly, which was used to build and equip Maggie’s Café, where members start off each day at the “Meet and Greet.”

Within the charedi [rigidly observant] community, there is a feeling that being a genetic carrier carries a stigma. For that reason, a system was developed as part of the Dor Yeshorim (DY) program that involves genetic testing of young adults before they begin to date, but also maintains a degree of anonymity.

The Dor Yeshorim policy on genetic testing stipulates: “Genetic screenings through DY are offered ONLY to unmarried and unengaged individuals who have not previously tested elsewhere. This protocol was implemented in order to avoid complicated situations that arise for already engaged or married couples who are presented with genetic incompatibility and to protect the confidentiality of all participants.”

This type of testing has been extremely effective in communities that rely on matchmakers, or where couples who have been tested consult with DY before becoming seriously involved. The DY approach to screening has helped to dramatically reduce the incidence of genetic diseases such as Tay-Sachs in the Ashkenazi Jewish community.

“Regarding Ashkenazi Jewish genetic screening, because of Dor Yeshorim, and how well the community is educated, it’s easier to talk to patients about it before pregnancy,” said Dr. Efrat Meier-Ginsberg.

Obstetrician/gynecologist Meier-Ginsberg, however, explained that Dor Yeshorim genetic testing may not always be useful. “It is hard as a physician to rely on Dor Yeshorim,” she said. “I don’t have the information on what they tested.”

Since they keep all results anonymous, only revealing whether a particular match is genetically compatible, the particular genetic defect carried by an individual remains a secret. The secrecy is meant to protect people from the stigma of being a carrier, but it also limits the usefulness of testing.

In addition, noted Meier-Ginsberg, “Dor Yeshorim does not test for all the genes. They stopped doing Gaucher disease.”

In the course of testing for carriers of the Gaucher gene, the DY testing inadvertently identified some people who actually had mild forms of the disease, but had not yet been diagnosed. “Then they were stuck,” said Meier-Ginsberg. “What were they supposed to do?”

Since the test was supposed to be anonymous and not identify or reveal what genes were positive, were they permitted to inform the patients, or not? Rabbi Joseph Eckstein, founder and director of Dor Yeshorim has said that the organization did inform those who tested positive for the disease. However, it is unclear whether all who tested for Gaucher’s over the course of several decades were notified, and this has become a point of controversy and contention for the organization.

The unexpected development led to a change in DY testing policy. The organization reasons that “testing the general population (and all DY participants) for Gaucher’s would serve only to create social stigma and discrimination to carriers and those affected, without the benefits that would come with a diagnosis, as asymptomatic or mild symptom patients are no candidates for treatment and report functioning similar to normal individuals who are not affected. For this reason, coupled with the likelihood of many more marriage matches being eliminated due to the high carrier rate, DY offers Gaucher’s test upon request only.”

Gaucher disease can manifest as anywhere from very mild with few or no symptoms, to severe. There is a treatment available called Ceredase, that is used when the disease is serious. It can cost upwards of $200,000 for the drug.

Thus, although testing through Dor Yeshorim can be valuable, as it screens prospective couples for many Jewish genetic disorders, including Tay-Sachs, cystic fibrosis, familial dysautonomia, Canavan disease, glycogen storage disease type I, Bloom syndrome, Fanconi anemia Type C, Neimann Pick, and mucolipidosis type IV, it does not test for Gaucher’s unless requested. Failing to provide individuals with a full panel of Ashkenazi Jewish genetic tests for serious genetic disorders may lead to serious problems for unsuspecting couples years later.

Miryam Z. Wahrman

If 19 genes are not enough to worry about, there are now companies that have developed approaches to test hundreds of genes at once. Signature Genomics of PerkinElmer Corporation has a new approach to genetic testing that is called the PrenatalChipOS. The technology, which involves a device called a DNA chip or microarray, permits the mass screening of many genes at one time. According to its website, it is “the most comprehensive clinically-relevant oligonucleotide-based microarray for diagnostic use.” The array is able to evaluate “over 200 known genetic syndromes and over 500 gene regions of functional significance in human development.”

Another company, Counsyl, advertises the Universal Genetic Test, that can replace “100+ single gene tests.” The tests range from ABCC8-Related Hyperinsulinism (more common in people of Finnish and Saudi Arabian descent), to Wilson Disease (common in China, Japan and Sardinia), but also includes a number of genes found in higher incidence in Ashkenazi Jews.

The company explains its “values” as follows:

“We believe that genetic testing is a human right, not a luxury. We believe children deserve healthy lives, free from genetic disease. And we believe in universal access, especially for those most in need.”

The website (http://www.counsyl.com) discusses their mission, “to scale up the Jewish community’s successful campaign of universal carrier screening for Tay-Sachs, which vanquished the disease by 2003….To do this, we seek to both make preventive carrier testing universally accessible and to use our resources to find cures and treatments for families suffering from genetic disease.”

Counsyl representatives recently contacted Bergenfield obstetrician/gynecologist Dr. Efrat Meier-Ginsberg, who reports that the test costs $350 to evaluate many more genes, and test for many more diseases, at a lower cost than the conventional tests.

“On one hand, more information is better. But sometimes that’s not the case, especially when you ask, what are you going to do with the information?” said Meier-Ginsberg. “I’m very wary. I think people will get more nervous.”

When many genes are considered at once, the chance of finding a defective form of a gene rises sharply. She suggested that testing for hundreds of genes could cause people to unnecessarily terminate pregnancies, because not every mutation in a gene causes defects or serious disease. Nevertheless, added Meier-Ginsberg, “Patients should have the option to know what’s available to them and then it’s their decision.”

“Ain l’davar sof [there is no end to the matter],” said Dr. Steven Schuss, a Teaneck pediatrician, referring to the hundreds of genes tested in the new DNA array testing. “It’s a quality decision, and it could be a financial decision.”

“Some people want to know everything about everything, and some will say, ‘just tell me what to do,’” Schuss added. “I don’t feel this is a decision I can make for a patient. It comes down to the individual personality of the patient. Real pediatrics is not cookbook.”

Testing so many genes could also unnecessarily stigmatize people, as every person carries some mutations in some of their genes. In addition, suggested Rabbi Lawrence Zierler of the Jewish Center of Teaneck, if traits other than disease genes are tested, it could lead to designer babies, with parents picking and choosing traits of their offspring.

As it is, said Zierler, “people want such perfection.”

He described how some in the rigidly religious charedi community go to extremes to investigate potential partners. “My mother works in an optometrist’s office and gets phone calls asking, ‘Is so-and-so a patient in the practice?’” he said. In the search for a perfect mate, “they want to get information on what kind of eyes they have and what type of prescription they have….These [genetic tests] are shifting sands, and it can be taken to a dangerous place.”

Wayne resident Shari Ungerleider, an advocate for Jewish genetic testing, cautions that genetic tests, like the DNA arrays that rely only on DNA analysis of saliva samples, could be missing critical genetic mutations in the Tay-Sachs gene. “There are places that advertise DNA through saliva, but with Tay-Sachs it is recommended that you do enzyme testing, as well,” said Ungerleider, whose son died from Tay-Sachs. There are more than 50 variants of the Tay-Sachs gene that are known, thus DNA testing will identify only up to 95 percent of Ashkenazi Jews who are carriers, and 60 percent of carriers in the general population.

On the other hand, blood tests that measure the levels of the enzyme hexosaminidase A have close to 100 percent accuracy in detecting carriers. “I don’t support just saliva screening for Tay-Sachs. Blood testing is needed; make sure with Tay-Sachs to do enzyme and DNA testing,” Ungerleider said.

“I believe in educating people about all that is available out there, being screened, and screened the right way, and letting them make the decision that is best for them,” said Ungerleider. “If they know, they can make the decision that is best for them.”

As new couples prepare to start their families, they can access genetic information at their fingertips. The Android phone has an application called Genetic Disorders, documenting 118 genetic diseases. A new iPhone “app” called GeneScreen provides the carrier frequency of 28 specific genetic disorders. It also provides an ancestry map showing which genetic disorders are more commonly found in different regions of the world. These expanded resources provide more information and more choices for couples; but these choices also lead to more ethical quandaries.

“I was in a situation where my husband and I were carriers, and we had an affected child,” said Shari Ungerleider, of Wayne. After Shari and husband Jeffrey lost their son, Evan, age 4, to Tay-Sachs in 1998, she became an advocate for Jewish genetic testing, and now serves as co-president of the New York chapter of the National Tay-Sachs and Allied Diseases Association, and vice president of the national organization.

She also works for the Jewish Genetic Disease Consortium, which educates people on Jewish genetic disease screening. One of the programs they run, “Couples Aware,” is a training program for rabbis and cantors. Raising awareness of Jewish genetic testing is more important than ever as DNA technology now makes it possible to screen for up to 19 defects that occur in the Ashkenazi Jewish community, as well as hundreds of other genes found in the general population.

“There are more and more carrier tests for more and more disorders,” said Teaneck resident Peggy Cottrell, a genetic counselor at Holy Name Medical Center, also in Teaneck. “Genetic testing is getting cheaper and cheaper to do.” Genetics departments at New York University and Mount Sinai Medical Center in New York, as well as in other medical centers around the United States, have dramatically expanded the panel of Ashkenazi genetic tests they can perform. Thirty years ago, it was only possible to test and identify Tay-Sachs gene carriers. Ten years ago, there were four genetic tests commonly done; that was expanded to nine five years ago; today, it is possible to test up to 19 genetic disorders found in the Ashkenazi Jewish population.

“The tests are available not because Jews are more likely to get [the disorders], but because there’s a unique mutation in the Jewish population,” said Cottrell. “In all these cases, there’s a mutation that is common to Ashkenazi Jews, so it makes it easy to do the screening, and the test is relatively affordable.”

Most genes occur in pairs, so it is possible to be a carrier of one defective gene, yet not have the disease, since the second copy of that gene functions normally. However, if both parents have a defective copy of the same gene, there is a one-in-four chance that their child will inherit both defective copies and be afflicted with a genetic disorder or disease. Thus, many couples get tested to determine if they are both carriers of a specific genetic defect.

The first genetic tests developed using DNA technology detected gene variants that were found at a higher incidence in the Ashkenazi Jewish population compared to the general population. For instance, Gaucher disease Type I has a carrier frequency of one in 15 in the Ashkenazi Jewish population. The Tay-Sachs gene occurs in one in 25 Ashkenazi Jews, and one in 20 Ashkenazi Jews can carry the familial dysautonomia gene. Tests developed more recently, however, are for “genetic defects that are very obscure, so the carrier frequency can be low,” said Cottrell. Those diseases include Walker Warburg Syndrome, found in one out of 112 Ashkenazis, and Usher Syndrome Type I, occurring in one out of 165 Ashkenazi Jews. Those genetic diseases are not unique to Ashkenazis, and, in fact “can occur just as often in other populations,” added Cottrell.

Dr. Steven Schuss, a pediatrician in Teaneck, reported that he addresses the issue of testing with parents as well as teenage patients who are beginning to date. “I don’t see a downside in testing for recessive genes because the person who has the gene is unaffected and it’s important to know if you are a carrier.” Schuss tells his patients to “make sure this is something you’ve thought about.”

Schuss explained that some in the charedi [rigidly observant] community feel that being a genetic carrier carries a stigma. They developed a system through the Dor Yeshorim program that works well in a community where couples meet through a matchmaker. It involves genetic testing of young adults before they begin to date. Before being introduced, both individuals are tested genetically, and assigned numbers. “It has a lot to do with confidentiality….You just need to know if the boy and girl are compatible,” he said. “They just give you a yes or no. If there are two similar recessive genes in the two of them, they will call it a ‘no.’” On the other hand, he said, “someone may be positive for the CF [cystic fibrosis] gene and if the other partner is negative they will report it as a ‘go.’”

The key to the success of genetic testing programs is getting young people to be tested before they are in serious relationships, as that gives them the most options. “I can’t imagine anyone against genetic testing before pregnancy,” said Rabbi Joel Pitkowsky, rabbi of Teaneck’s Conservative Congregation Beth Sholom. “Every health insurance should cover it; it should be encouraged for all couples who are thinking of getting married.”

“In premarital counseling I discuss it,” he said. “When a couple discovers they are both carriers of a terrible disease, they have a difficult decision to make. It is a difficult discussion, but it is worth having the discussion before the woman gets pregnant.”

Dr. Efrat Meier-Ginsberg is an obstetrician/gynecologist who practices together with her father, Dr. Ronny Meier. Their Bergenfield office serves many Jewish patients in the Teaneck/Bergenfield area.

“I do recommend that testing be done,” said Meier-Ginsberg. “I give patients options. I tell them what tests are available.”

“I recommend it highly when they are dating and when they are engaged. Once they are pregnant, if they are a carrier, I recommend that the husband be tested, as well,” she said.

If both partners are found to carry the same recessive gene, there are tough choices to be made. “Even if they are dating, it doesn’t mean that they have to break up the relationship. They have the option of IVF and PGD,” said Meier-Ginsberg, referring to a couple’s option to conceive embryos by in vitro fertilization, i.e., by mixing the man’s sperm and the woman’s eggs in a petri dish. The embryos generated this way can be tested in the laboratory for genetic defects, and those found to be free of the defect can be chosen and implanted into the mother’s uterus. This permits the couple to have biological children free of that disease, without risking a pregnancy with an affected fetus and the difficult choices that might ensue.

When a couple discovers during pregnancy that both are carriers, they are faced with a daunting decision. “Regarding testing a pregnancy, different rabbis may give different advice,” said Schuss. “A couple should never make assumptions about the halachic p’sak [Jewish legal ruling]. Behind the scenes, abortions have been recommended. They may permit it, as mental health is health, too.”

“There’s always the question of the benefit, or the tyranny of knowledge,” said Rabbi Lawrence Zierler. “We are going to find people faced with very difficult decisions.”

Zierler, who is rabbi of the newly Orthodox Jewish Center of Teaneck, also serves on ethics committees at Holy Name Medical Center, and chairs the ethics committee for the Hospice of New Jersey. Regarding genetic testing, he said, “They are going to have an awful lot of information. When you have information, what are you going to do with it? You need social supports.”

Zierler recommended that the community develop religious panels to guide individuals in these decisions. “The weight of these kinds of decisions should not rest on one rabbi alone. There are a certain number of rabbis who have the ability to digest and interpret the parameters of the science and the statistical information that people have to understand,” he said. He suggested that the yoetzet halachah [female advisor on Jewish family purity issues, a position found in some modern Orthodox synagogues] could be involved on such a panel. “Their role should be expanded to that,” he said. “It’s a logical place to begin.”

“Like it is with all good medicine, the modern Orthodox will want to have this testing,” said Zierler. “It’s good medicine to have an awareness, but what do you do with the information? There’s an element of psychotrauma that comes as a result of the information.”

“Dealing largely with a modern Orthodox congregation, many people make decisions independent of the rabbi,” said Zierler. “But rabbis can be very creative. We find solutions. No two situations are entirely the same; they have to be considered on their own merits.”