Hope, Persistence, and the Power of a Mother’s Love

The Landsman Family Fights for a Cure for Their Sons With Canavan Disease 

For Gary and Jennie Landsman, their marriage in May of 2015 was a second chance, an opportunity for a fresh start. They had both been married previously, and Jennie had one son, then-5-year-old Michael, and they now looked forward to building a large family together.

Just over a year later, in June 2016, their beautiful son was born and their joy was complete. Benny, as they named him, was a delightful baby. By the time he was three months old, he had passed the difficult colicky stage and Gary, Jennie, and big brother Michael loved to cuddle him and make him laugh. It was a glorious time in their lives.

At a family Chanukah party, when Benny was six months old, Jennie’s sister, an occupational therapist by profession, who hadn’t seen Benny in a while, commented, “Does he usually need this much support when sitting?” Jennie was surprised. “I had always seen him as an exceptionally cuddly baby, but my sister thought that he should be holding himself better at that age. Since my sister works mostly with adults, I asked a friend who was an OT for children, and she encouraged me to get him evaluated. I made an appointment with a local Early Intervention office for an evaluation, and figured he might need a bit of therapy to help him strengthen his muscles. I also made an appointment with a neurologist, just in case,” she says.

Since she was looking carefully at his development then, she realized that Benny had plateaued. He wasn’t doing anything new developmentally, although he continued to be very sociable and responsive to others. “He rolled over a few times but wasn’t starting to swim around or crawl. I couldn’t compare him to Michael, who had been crawling at this age, because I knew that was exceptionally early,” she says.

The neurologist wasn’t too concerned. He told Mrs. Landsman to try some occupational and physical therapy and come back in a month or so to see if he’d made any progress. After a month of no progress, she took him to the head of pediatric neurology of a hospital and to an ophthalmologist to check out his eye tracking issue. Everyone said the same thing. “Some kids are a little delayed. Come back to check in a few months.”

Benny’s loving personality also threw off his parents and the doctors. “He was such a happy child, so social and responsive. He reacted to sounds very quickly; he would get so excited when the door opened and someone came in. He seemed very aware cognitively, and just delayed physically, which seemed like something that would resolve itself soon enough.”

Mrs. Landsman didn’t want to be “that mother” who gets hysterical over every delay in her child, but as time went on, Benny’s delays were getting harder to ignore. She booked him for an MRI, and the doctors did so much bloodwork, they had to do it in batches because his blood volume wasn’t large enough at that age to do it all at once. In between, they dealt with insurance delays and one doctor retiring, which further delayed the process of diagnosis.

By July 2017, when the Landsmans finally got their answer, Benny was over a year old and their next son, Josh, was two weeks old. After all their expensive and exhaustive testing, the results came by way of a simple urine test; there was a buildup of NAA in his urine, something that occurs with enzyme deficiency.

“The doctor, who was on vacation at the time, made us an appointment with a geneticist at the hospital that day. There we met with a nurse who nervously took family history details from Gary and me. Eventually the geneticist came in and told us that she believed Benny probably had Canavan disease, a rare genetic disease. She gave us that nebach look as well as some paperwork about Canavan disease. I was naive. When I heard it was an enzyme deficiency, my first question was, ‘When can he start taking an enzyme supplement?’” Her initial relief that Benny just needed something supplemental faded quickly when the physician explained that there was no treatment or medication for Canavan disease, only supportive care. “They basically told me to take him home, make him comfortable, give him some therapy, and wait for him to die.”

The doctor said the diagnosis could be confirmed with a blood test and asked them to test newborn Josh as well as Benny because, she explained, there was a one-in-four chance that he had it too. Two weeks later, the results came in. Josh had Canavan disease too. Their world collapsed. The dream was over. With two children who had a life expectancy of 3-10 years, the Landsmans were crushed.

In retrospect, Mrs. Landsman says, there were tiny signs that something wasn’t right, but at the time, they dismissed them as simple delays, normal baby behavior. “His colic turned out to be neurological; irritability typical of Canavan disease. While he responded well to people, he couldn’t track well and suffered from nystagmus, or eye shaking, but it only happened when he was tired, and the pediatrician didn’t think it was a big deal. It turned out to have a neurological cause too.”

Jennie admits that she spent the first few weeks after the diagnosis just crying, in a depressed state. “You want to do everything for your kids, but in this case, we were told there was nothing to do but wait. I was so devastated. I was in a dark place. I was basically mourning my hopes and dreams for my children.”

Then one day, while rocking Benny to sleep for a nap, tears streaming down her face while she wondered how many more times she would hold him, he looked up at her and started laughing. “At that point, I told myself that I couldn’t just cry for the next 3-10 years. I would just enjoy every moment I DID have with them and focus on the here and now.”

She started doing research on Canavan disease and found out about an experimental gene therapy. There were only two scientists studying Canavan disease, partly because it is so rare, but also because any drug to cure it wouldn’t be profitable for the pharmaceutical companies. However, Jennie learned that studying Canavan disease can also help advance researchers’ understanding of other neurodegenerative diseases such as Parkinson’s, ALS, and Alzheimer’s, so some research was being done.

She also learned that many Ashkenazi Jews are carriers of the Canavan disease gene, a recessive gene which only affects children if both parents are carriers. Jennie had done private genetic testing, including the standard Ashkenazi panel and additional testing, and was told she wasn’t a carrier for anything, so she knew she could marry anyone, no matter his carrier status. After the diagnosis, she went back to check her records. It turned out that the lab had only sent the results for the additional tests and not the Ashkenazi diseases, so when the doctor said everything was fine, he hadn’t included Ashkenazi diseases, including Canavan disease. This was a mistake both on the lab’s part and on the doctor’s part for not realizing that the results were incomplete. (Ed note: Dor Yeshorim, the pre-marital screening organization, includes Canavan disease in their standard testing for Ashkenazim.)

Through intensive research, connecting to other families with children suffering from the disease, and open hashgachah pratis, the Landsmans got in touch with Dr. Paola Leone, a researcher who, after meeting the Landsmans, agreed to try and help them. Working with Leone and neurosurgeon Dr. Chris Janson, they are taking steps to try to get a clinical trial for gene therapy set up for Benny and Josh, as well as a few other children with Canavan disease.

There were and still are dozens of hurdles and setbacks in their path. Due to a contamination problem with another unrelated gene therapy trial, the FDA has tightened the requirements for experimental treatments and is very strict and won’t easily approve new trials. This added to the challenges for the Landsmans and their doctors as they worked to submit a request to the FDA to approve the use of an experimental new drug for “compassionate use” (also known as “expanded access”), a category for cases like the one Benny and Josh fall under, because there is no known treatment cure and a life-threatening prognosis for their disease.

But these experimental treatments are not covered by insurance and drug trials are prohibitively expensive. Gary and Jennie, a small business owner and a part-time yoga and martial arts teacher respectively, don’t have millions of dollars to pay for the treatment; they rent their home and have no financial backing for amounts this large. No drug company is interested enough to sponsor it, but they would not let this deter them. Instead, they went public, via social media and with the support of thousands of people, many part of the greater Jewish community, and raised close to a whopping 1.5 million dollars to cover what they originally estimated to be the cost for the trials. But much more money is needed and the clock is ticking, because the drug must be tested on animals first. And even if they raise the money, they still need FDA approval.

Up until recently it seemed the FDA would be one of many hurdles for the Landsmans. But following outreach to the FDA by concerned politicians, and after lots of political pressure and months of waiting, representatives from the FDA agreed to meet with the Landsmans and their research team. They met with representatives from the FDA at headquarters in Washington, DC, this past Chol Hamoed Pesach. Prior to the meeting, the Landsmans had to submit a list of requested participants. Though they weren’t sure if their request would be approved, the Landsmans included Benny and Josh on the list of people attending the meeting. Though she was told it was unprofessional to bring children into such a high-level meeting, Jennie insisted on bringing Benny and Josh with her. “I want them to see that there are real people behind this request, we’re not just a case number or a pharmaceutical company. I wanted them to see their sweet faces. How could they say no to them? Just let them try to say no to such cute faces,” she said.

The Landsmans didn’t know what to expect as they took their seats at the table with the boys on their laps, surrounded by FDA review board members, their research team, doctors, FDA consultants, and lawyers. The meeting was intense as they reviewed many of the sticking points that had previously prevented them from moving forward. After much discussion and back and forth, they cleared up many of the issues and the FDA approved the drug manufacturing and the submission of the IND (Investigational New Drug) protocol. Although they acknowledge that they have many hurdles ahead, the Landsmans are confident that they are now on the same page as the FDA and believe they have cleared one of their more challenging hurdles.

“I think that bringing my children changed the course of the conversation. It wasn’t just case number XYZ, but an adorable child on my lap, with a mother who would give anything to help him,” says Jennie. “After the meeting, many people approached us and told us how touched they were, and that they would help us get this approved.

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Gene therapy as a means of treating rare diseases is relatively new, but rapid advances in technology and research have made genetic treatments very popular in recent years. Since successfully finding a genetic treatment for studying Canavan disease can help researchers find cures for other diseases, the best-case scenario would be if a pharmaceutical company took interest in the gene therapy and wanted to produce it. But so far, the pharmaceutical companies have not taken any real interest, leaving the Landsmans on their own, to reaching out to kind community members and strangers in a quest to save their children.

Taking care of Josh and Benny is a full-time job. Jennie is grateful to New York State’s generous early intervention assistance, which covers her sons’ occupational, speech, physical and feeding therapy. Their daily schedule is quite full, between appointments and therapies, and Benny recently had a G-tube inserted because he was having trouble eating and was not getting his necessary nutrition. Jennie recently shut down her yoga and martial arts studio to care for the boys full time, but still teaches some classes including yoga and acrobatics at her shul to both longtime and new students on the side so she can get out a bit.

They recently formed a new charity to raise the money for a cure for Canavan disease — for the expensive trials which offer hope for her children. “I don’t want any other mother to have to go through this; I hope to make treatment accessible for all families in need.”

About her extraordinary efforts to help her children and others, Jennie says humbly, “I’m just a mom, and mothers do anything they can for their children.”

There is a “GoFundMe” page: gofundme.com/savebennyandjosh

Please daven for Shalom Binyamin Ben Shayna Toyba and Yehoshua Natan ben Shayna Toyba.

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What is Canavan Disease?

“Canavan disease is a rare genetic neurological disorder characterized by the spongy degeneration of the white matter in the brain. Affected infants may appear normal at birth, but usually develop symptoms between 3-6 months of age. Symptoms may include an abnormally large head (macrocephaly), lack of head control, severely diminished muscle tone resulting in “floppiness,” and delays in reaching developmental milestones such as independent sitting and walking. Most affected children develop life-threatening complications by 10 years of age. Canavan disease occurs because of mutations in the aspartoacylase (ASPA) gene that affects the breakdown (metabolism) of the N-acetylaspartic acid (NNA). It is inherited as an autosomal recessive condition.”

Source: NORD, National Organization for Rare Disorders

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What is Gene Therapy?

Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including:

Replacing a mutated gene that causes disease with a healthy copy of the gene.

Inactivating, or “knocking out,” a mutated gene that is functioning improperly.

Introducing a new gene into the body to help fight a disease.

Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently being tested only for diseases that have no other cures.

Source: National Institutes of Health