Parents of children with attention and concentration problems struggle with difficulties such as misdiagnosis, ineffective medication or drugs that cause side effects. Only a few of them decide to delve deeper into this world and coming up with an innovative remedy that works for their child.
Birkat Klimshtein-Levy and Hagay Levy are the parents of four children living in central Israel. She is an architect and owner of a company that manages planning and construction projects; he works in finance and business development in the high-tech world. After receiving a recommendation from one of their children’s schools, they decided to send their child for assessment for attention-deficit hyperactivity disorder (ADHD). They went through the usual procedure at a child neurologist’s office, which included a meeting of the child and parents with a doctor, filling out questionnaires and further testing.
Following the diagnosis, the child started taking a drug meant to treat the disorder. He became calmer during classes but still couldn’t manage to read or write.
“This is a super-intelligent child,” says Klimshtein-Levy, “we were less interested in his grades, more on his feelings and our concerns that he would grow up frustrated.” After the child switched medications, he started making serious progress in his studies. “His life became quite normal,” say his parents. But at this point, at which most parents would have returned to their normal routines, the issue did not give Klimshtein-Levy peace of mind.
“We noticed that other than the child’s age and weight, there was no personalization of the medicine to fit children’s different and specific needs. It seemed very puzzling that in this day and age of technology, this treatment was more hit-and-miss, more an art than a science. In fact, you’re told to try ADHD medicine first, and if it works, great, and if not, come back in a few months, there are no waiting lists. By the time parents are mentally ready to give their kids medication, it’s easy to abandon it if it’s not effective. There really are high numbers of people who quit, and this is something that could determine a person’s life course,” she says.
The common drugs for attention disorders in Israel are methylphenidate and its derivatives, Ritalin, Ritalin LA, Ritalin SR, Focalin and Concerta (the last four being longer-acting). These drugs are stimulants that were found to be effective for 70 percent of their users, but they have side effects such as headaches and stomach aches, depression, loss of appetite and more. Another group of drugs that are also stimulants (amphetamines) include Vyvanse, Adderall and Adderall XR. A third group, which works through a different mechanism, includes the drug Strattera (Atomoxetine). These drugs are less effective, but they have fewer side effects. The U.S. and Europe have a wider range of available drugs for this disorder.
A ‘revolutionary method’
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Between 5 and 10 percent of children around the world have attention problems. “In Israel, it’s closer to 10%,” says Dr. Lilach Shemer-Meiri, the head of the Clalit HMO and the Carmel Medical Center’s neurodevelopmental network in the Haifa and Western Galilee area. “Up to 66 percent of them become adults with attention problems. The problem is that this affects all aspects of life, at home, in the classroom, in interacting with friends – at each age, the effects are different,” she says.
This disorder involves a disruption of a physiological mechanism, which is why treatment involves medication, she says. “Currently, diagnosis includes an interview with the child and his or her parents, questionnaires filled by a teacher, and often a TOVA test, which is a computerized test for the effectiveness of a drug, or others like it. However, these are one-off tests, not repeated on a continuous basis.
“If a child is diagnosed with an attention disorder, for me, the next stage is the more challenging one: finding the right treatment, getting the child balanced and on track, finding the equilibrium between a drug that helps and a drug that causes side effects and finding the correct drug in terms of the duration of the problem and its symptoms (i.e., whether they involve attention deficit, hyperactivity, impulsiveness). I begin a journey with the family and child, but ultimately, when I try to assess the effectiveness of a drug, my tools are very limited,” says Shemer-Meiri.
Personalized ADHD treatment
“I’m a very curious person, and I became obsessed with the issue,” says Klimshtein-Levy. “I read academic studies and discovered that many of them found a link between physiological parameters such as a person’s pulse rate and mobility and their attention span. But every study looked at only one parameter. At this point I recruited Haggai. We asked friends who were involved in this area and I took a course on brain physiology. I felt that I needed to understand this issue in depth.”
One evening, while they were hosting some friends and the children were running around in the background, “I said to my friend: it’s too bad one can’t measure levels of attention. I remember this moment precisely, thinking: actually, why not measure it?” she relates. “At that moment, the obsession became something one could address. The next day I started calling friends and thinking of how to make this happen. We held many meetings with physicians, and from all of them we heard: we wish there was a product that measured attention. That was three and a half years ago.”
Klimshtein-Levy and her husband had their child wear a smartwatch that monitored physiological parameters under three situations: with no drug, with a drug that didn’t help and with a drug that did help. The data collected by the sensors was given to Prof. Liran Carmel, a world-renowned computational biologist from the Hebrew University, with the idea of trying to see if one could distinguish physiological differences. Carmel, says Levy, analyzed the data and clearly saw differences between the three conditions.
“Bracha and Hagay came with the idea of a smartwatch and we conducted some tests,” says Prof. Carmel. “We immediately saw that the sensors were rich with information, changing significantly with and without a drug. We realized there was a lot of material to work with,” he says. Carmel still accompanies the project, giving his advice on the algorithms used for testing. Also accompanying the project is Prof. Itay Berger, a pediatric neurologist and a recognized expert in the field.
After they saw the graphs drawn up by Prof. Carmel, “we concluded that what the teacher’s eye couldn’t detect Carmel could see using mathematical models. We then said: that’s it, we have a company here,” says Levy. They set up one called Iluria, with Haggai as CEO and Klimshtein-Levy as its director.
In 2019, the company held an experiment, with the help of a grant from the Innovation Authority, in collaboration with the Clalit and overseen by Dr. Shemer-Meiri. Some 37 children, aged 7 to 12, took part in the experiment, all of them diagnosed with ADHD and responding well to medication. The children took a TOVA test with and without the drug, and the smartwatches they wore registered parameters such as mobility, angular mobility, changes in heart rate, skin temperature, and more. After analyzing the data, it turned out that for 25 of these children, it was clearly obvious whether they were on or off the drug.
These excellent results led the company to conduct another experiment, a more comprehensive one which has just ended, at the Cincinnati Children’s Hospital Medical Center in Ohio. In this experiment, children wore the watch throughout the day. In the Israeli experiment, the results showed whether at a given moment a child was above or below a certain point on the graph, with or without a drug. In the Cincinnati experiment, one could see the trend throughout the day, such as when a drug kicks in, when it peaks and when its effect subsides.
The aim of this technology is not to replace physicians but to be a supportive tool when they make decisions. “The experiment in Cincinnati showed that with algorithms one can produce individual graphs indicating the effects of a drug on every child, including the extent and duration of such an effect. This means that the level of treatment can now improve significantly,’ says Levy.
Technological developments in recent years have led to the establishment of companies that aim to diagnose or treat attention disorders using innovative methods.
One of the more prominent ones is Cognoa, a company in Palo Alto that deals with diagnosing and treating children by digital methods, using big data. The company focuses on autism, ADHD, language development and anxiety. For obtaining a diagnosis, parents have to fill in a questionnaire using an app and then send a video showing the child. The company says that these are kept securely, with the diagnosis sent to the parents within days.
The field in which the company had the most success is with autism. A breakthrough came in early July, when its digital diagnosis for autism received U.S. Federal Drug Administration approval. The company has so far raised $53.9 million.
Another interesting company is Peak Profiling, born in the Faculty of Mathematics and Musicology at Humboldt University in Berlin more than a decade ago. The company is developing algorithms to identify emotional and physical conditions – among them ADHD – based on sound only.
Its technology is based on analysis of audio segments (mainly the human voice) by means of musical parameters associated with rhythm, diction, volume, melody, tone and others.
Another company that has received quite a bit of attention is Dr. Adam Gazzaley’s Akili. Gazzaley is one of the leading brain researchers in the world and heads the research laboratory Neuroscape at the University of California. Gazzaley developed the first computer video game intended to help children with ADHD and won FDA approval.
The game, Endeavor, is defined as a medical treatment – and therefore it requires a doctor’s prescription. The treatment is given to children with ADHD between the ages of 8 and 12, in a dose of 25 minutes per day, five days a week. Last year, Gazzaley told Haaretz that he and his team had wanted to check all aspects of the game – safety, side effects, advantages using a placebo group and other aspects, and only then did they submit it for FDA approval. Their goal, Gazzaley said, was to define Endeavor as a digital medication.
Big data deficit disorder
Iluria, the Levys’ company, submitted its technology for FDA approval and it is in the advanced stages of registering a patent in the U.S., EU and elsewhere. The company is now in the phase of raising seed money that will allow it to develop its software as a product. Iluria, which among other things uses a crowd-funding platform, will ask Israel’s Innovation Authority for funding. “It’s hard to raise money in Israel in the medical field; it’s considered much riskier,” Klimshtein-Levy says.
According to Klimshtein-Levy: “Angel investors invest according to their personal expertise and experience, usually in the areas where they themselves have made their fortune. In the U.S., three angels associated with an accelerator in Dallas in which we took part in and who know the medtech field invested. In Israel some people said the solution was interesting but they didn’t specifically understand the field of mental health, the business model and the regulation connected to it.”
Iluria’s business model is based on billing U.S. insurance companies, which will save huge amounts of money if treatments for children with ADHD are more effective. “The main money that insurance companies pay out is not on medication, but numerous visits to neurologists and psychiatrists, as well as on complementary treatments that increase the less precise the medications are, “ Klimshtein-Levy explains. “The intent is that the insurance companies will pay for every child who uses the software.”
In two weeks the company will begin another pilot program in Europe that will actually be an expansion of a pilot they did for the Clalit, and will include more groups of patients in terms of age and gender. “Our final goal after many children have used the product, is that by big data we can recommend ahead of time which children will use the watch, what medication suits them according to data on other children they share similarities with,” Levy says.