Funding medical miracles to save young lives
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Funding medical miracles to save young lives

Gene therapy trials on Canavan disease need support

Clockwise from top left, Gary, Jennie (holding Evan), Jennie’s son Michael,  Benny, and Josh.
Clockwise from top left, Gary, Jennie (holding Evan), Jennie’s son Michael, Benny, and Josh.

Rise Landsman of Teaneck and her family are on a crusade to save her two small grandsons, Benny and Josh, who suffer from Canavan disease.

The Landsman family is working to promote a new gene therapy treatment that could change their lives and the lives of a group of children with Canavan. If it is successful, the novel approach to gene therapy could cure thousands of people around the world who are afflicted with a variety of genetic defects. A scientific team already is working on this cure, and the FDA is on board, but the investigators still need funds to produce, test, and apply the promising experimental procedure to the small patients.

According to Ms. Landsman, the research team needs $1 million by the end of October and another $1.5 million by the end of December to make its potential cure a reality. Such large sums of money are necessary to bring cutting-edge research into the clinic as safe and effective therapies and cures.

“The story is the great success we’ve had to date with people, strangers and friends, coming forward to support the cause,” Ms. Landsman said. The program has been expanded “from trying to save two kids to saving 10 kids, with a global campaign.”

Benny, 3, and Josh, 2, are two of thousands of patients worldwide, many from Ashkenazi Jewish families, who are born with the flawed ASPA gene, a gene whose task it is to make a critical enzyme, aspartoacylase. Children without ASPA activity have a toxic chemical called N-acetyl-aspartate (NAA) accumulate in the brain, and it damages their brain cells. Children born with severe Canavan disease begin life normally, but soon the consequences of the genetic flaw interfere with their development, and they fail to reach milestones in physical and mental development. Loss of movement, intellectual disabilities, and seizures occur in these children, and they rarely live beyond the age of 10.

Scientists have been attempting to develop effective therapies for Canavan disease for decades, with limited success. In 1999 the first gene therapy for Canavan was performed on 16 patients using the ASPA gene enclosed in a microscopic lipid casing. The patients showed some minor improvements but were not cured. Dr. Paola Leone, who was part of the team that performed that experimental treatment, learned back then that the delivery system was not optimal. She is the lead investigator in the current project, now based at Rowan University in Glassboro, whose goal is to develop new gene delivery mechanisms and a therapy regimen that works.

The road to a cure using gene therapy has been a bumpy one. Twenty years ago, another gene therapy trial on another disease led to the death of a young patient, Jesse Gelsinger, who died from complications after treatment. Although that case was unrelated to the Canavan trials, his death led to a halt in research, and it took years to regain the momentum and approvals needed to apply gene therapy once again to human patients.

Dr. Leone has spent the past 20 years investigating a better way to safely introduce genes into patients’ brains. She and her team now are ready to treat the children with gene therapy using a new vector, or delivery system, that targets the white matter of the brain. The ultimate goal is to protect and correct neurons, the brain cells affected by the ASPA gene.

Benny was born in June 2016; by the time he turned 1, his parents knew there was something seriously amiss. Around his first birthday and shortly before his brother Josh was born, Benny was diagnosed with Canavan disease. When Josh was born, his parents, Jennie and Gary Landsman, did not hesitate; they tested the newborn, who was, sadly, also found to have the disease.

Clockwise from top left, Rise and Dan Landsman hold their grandsons, Josh and Benny.

Faced with caring for two babies with Canavan — a devastating disease, with no hope for long-term survival — the Landsmans took on the challenge with deep determination; they decided to do everything possible to fight the disease for the benefit of their sons and other Canavan families. Jennie and Gary had a mission, which focused on getting all the services their children needed, and moving gene therapy, a potential cure for the disease, out of the lab and into the clinic.

Rise and Dan Landsman, Benny and Josh’s dedicated grandparents, are longtime Teaneck residents who are planning to make aliyah to Israel next year. Rise Landsman reports that 3-year-old Benny cannot communicate, sit, stand, or walk, and he’s on a feeding tube. Despite all these limitations, he has started school at Stepping Stones in Queens, and his grandmother says “he is happy and seems to be doing well.”

Two-year-old Josh is doing better developmentally than his older brother, because the family learned about his diagnosis when he was a newborn. “Breast milk has the [missing] enzyme, so he was on breast milk the whole time,” Ms. Landsman said. “Josh works very hard to keep his head up. He can sit a little bit, engages in his environment, and reaches out for things.”

What can a Canavan family do to ensure future children will be healthy? When Jennie and Gary decided to have another child, they had planned on using in vitro fertilization, followed by preimplantation genetic diagnosis so they could identify and choose healthy embryos to implant. But before that could be arranged, Ms. Landsman said, “Jennie found out she was pregnant.”

The couple did genetic testing of the pregnancy and learned that the fetus was a carrier, with one copy of the Canavan gene, like his parents, but that he would not have the disease. Their son, a healthy baby boy named Evan, was born on May 20, 2019.

Meanwhile, in April 2019 Canavan researchers moved forward with their work and met with a group from the FDA. That federal agency greenlighted the procedure to produce the plasmids — genetically engineered DNA molecules with the healthy ASPA gene. It is expected that after the plasmids are ready in the next few weeks, they will be tested more. “We will have the laboratory ready in October or November to begin vector production,” Ms. Landsman said. (A vector is a virus that has been modified to eliminate any ability to cause disease. It can deliver DNA into the patient’s cells.)

“We hope and expect that the vector will be completed by the end of December,” she continued. “Then in January or February we hope to get definitive approval from the FDA to go through brain surgery protocols.” The vector containing DNA with the healthy gene has to be inserted next to the brain cells. The surgery involves drilling four holes in the skull to enable delivery of the “white matter seeking virus” to the brain cells. “We have conditional approval from the hospital,” Ms. Landsman said.

Back in November 2017, Jennie and Gary Landsman and their family had to make a difficult decision about the boys. At that point it would have been easier to request approval for one child to be part of the study. But they had two children with the disease, and “we didn’t want to be like Sophie’s Choice, so we requested that Dr. Leone expand access to the technique to a small group of children,” Ms. Landsman said Other families with Canavan children wanted to join the group. “Right now we hope and pray that we can raise the money.”

Ms. Landsman listed names of some of the group, who are from all over the world: Benny and Josh from Brooklyn, Tobin from Iowa, California twins Yael and Yoel, Artyom and Olga from Russia, Marguerita from Italy, and Malgosia from Poland. She reported that families in Russia, Italy, and Poland have raised $2 million, “and we gave $1.5 million” from funds raised here, she said. “We need to raise another $2.5 million, including one million dollars by the end of October.”

Ms. Landsman has been asking rabbis in the area to publicize the need for funds. “I just sent a letter to Rabbi [Yosef] Adler asking him to ask colleagues in the RCBC to publicize the fundraising.” Several rabbis in Manhattan and Brooklyn also are pursuing this.

“We hope and pray Benny will be treated with approved gene therapy in February or March,” Ms. Landsman said. “Our campaign to save two kids has now become a campaign to save 10 kids.”

The researchers also will submit an IND —an Investigational New Drug application — which makes the procedure available to anyone with Canavan but also will be a platform for treating other diseases, such as ALS, Parkinson’s, Alzheimers, and brain cancer.

“Dr. Paula Leone and her husband, Jeremy, are totally committed to finding a cure for Canavan,” Ms. Landsman said. “They chose not to have a family. The kids with Canavan are her family. She goes to birthday parties for those kids.”

Although the sums needed seem overwhelming, Ms. Landsman has hope. “We had a fundraising event in Deal, in August, and half a million dollars was pledged to the campaign. When the host pledged $200,000, he said, ‘we are a very, very rich community, and it is our obligation to give back.’”

Ms. Landsman said that the money raised will be directed to a federally approved 501C3 fund, the Cure Canavan Fund, to be used for research and development of the cure. (https://curecanavanfund.org)

Rise Landsman is asking for support for an approach that holds out much hope for her precious grandsons and so many more youngsters. “In a video of one Canavan patient, Dolly, we see Dolly can walk with a walker and say ‘mama,’” she said. “She is expressing a little bit of the enzyme. Even with a little bit of enzyme production neuromuscular function is possible. We hope that the enzyme will be expressed from the new genetic matter.”

Dr. Miryam Z. Wahrman, the Jewish Standard’s science correspondent, is a professor of biology at William Paterson University, where she conducts research on microbiology, public health, and bioethics.

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