Israeli scientists have identified drugs that may help an American toddler with a rare and currently untreatable brain disorder, before it causes him severe disability and reduces his life expectancy.
Scott Reich, a Jewish lawyer and academic from New York, turned to Tel Aviv University in desperation after being told that his son Eli, age 2, has FOXG1 Syndrome.
The genetic condition causes inadequate production of the FOXG1 protein, which the brain needs in order to grow. People with the syndrome tend to have serious disability, caused by limited brain development, and few live beyond their teens.
His parents have described the diagnosis as “like receiving a repeated punch to the gut.” They wrote: “You gasp for air; you cry; you scream; you grieve; you ask questions. How? Why? What kind of life will Eli have? What will his capabilities be? What is his life expectancy?”
For 15 months, a team at TAU’s Blavatnik Center for Drug Discovery has been screening a library of 7,000 FDA-approved substances. Using DNA from Eli — and protein from a firefly — they have identified five drugs they say are likely to help him and some of the other 700 children and teens diagnosed with FOXG1.
“When we heard the devastating diagnosis, I said to my wife Ilissa: ‘We have to go to Israel,’” said Reich, who launched the Tel Aviv research in parallel with research at a handful of US universities. “In Israel, we’ll find the know-how, experience and out-of-the-box thinking that we need.”
Now, he is more hopeful than at any point since the diagnosis, and optimistic that the drugs will pass animal testing and can soon be administered to his son. “I’m praying for a breakthrough,” he said.
Lead researcher Dr. Eddy Pichinuk told The Times of Israel: “We have identified several drugs that can be used to treat Eli’s condition, limit its impact, and hopefully extend his life expectancy. We now need to validate them in animal models so we are preparing mice with the same mutation that he has, and it will take several months.”
“Time is very critical because the window of opportunity is closing, but we hope that we can get the drugs approved for him in time, before the completion of his brain’s development, after which point drugs wouldn’t be effective,” Pichinuk said.
The search for personalized treatments for rare diseases is not new, but remains a niche field. In this case, the screening method involved using a protein from fireflies to replace the faulty protein in the DNA of cells from Eli. Aspects of the firefly protein’s behavior in response to drugs are similar to that of FOXG1, which makes then a useful tool, said Pichinuk. What is more, the firefly protein is luminescent, which enables researchers to closely monitor how it acts.
He said that the approval process for the drug or drugs that perform well in animal testing will be quick, as it will go through the FDA’s compassionate treatment channel given that the medicines are already considered safe — at least for adults. They are currently used to treat a range of diseases, such as cancer, psychiatric disorders, and various inflammatory syndromes.
As the animal testing is taking place, Pichinuk will conduct further research to assess the drugs’ suitability for Eli. He will use advanced methods of genetic engineering to transform his skin samples into stem cells and then into brain cells. This will allow advanced assessment of how the drugs will impact Eli’s brain.
Believe in a Cure, a 501(c)(3) nonprofit foundation set up by Reich with a $7 million fundraising target, commissioned the Blavatnik Center to undertake the research. The center’s chief scientific officer, Dr. Avi Raveh, told The Times of Israel: “We can’t help in every case and with every disease, but here there was a chance, and now I’m very optimistic. As time goes by I feel more pain and frustration for the family, but I admire their positivity.”