The mission of IDefine is discovering life-changing treatments and cures for those with intellectual disabilities stemming from genetic disorders. It’s a monumental undertaking, but one that is being guided by its Scientific Advisory Board (SAB) consisting of expert scientists from around the world.
Paul Smith, the initial member of IDefine’s SAB, comes from a true multi-national family. Paul is British; his wife, Valeriya is Russian; and their oldest son, Edward, was born in Switzerland. When Edward was only two-months-old, the family moved to Delaware where Paul took a job leading Incyte Corporation’s non-oncology discovery research, with a primary focus on autoimmune and inflammatory diseases.
A few months later, Edward was diagnosed with Kleefstra Syndrome.
“I remember me and my wife getting back in the car with our son, and I lost it,” Paul said. “I turned to my wife and said, ‘I make drugs for a living and I don’t know what this disease is, I’ve worked in neuroscience my whole life and I don’t know how to help him.’”
Because Kleefstra Syndrome is rare, it was not something the pharmaceutical industry had active programs on, so Paul began investigating who was working on it and how he could help.
With IDefine’s SAB, he says he’s found his people.
“I’m not just a guy on a scientific advisory board helping out with some scientific questions,” Paul said. “I’m a parent, I see them as my friends, and I see them as people with a common goal and an infectious energy. I want to be working with them, it’s not an obligation.
The IDefine SAB has attracted dedicated scientists and medical experts from across academia and the biotech industry, with all involved volunteering their time. Using Zoom virtual meetings, SAB members can rapidly respond to new publications, scientific discoveries and advice on IDefine’s scientific strategic priorities. The SAB also has an important role in reaching out to innovative biotech companies and research teams at universities around the world.
Working closely with IDefine founders Geoff Ryne and Eric Scheeff, the SAB primarily focuses on exploring possible treatments to directly address the loss of function of one copy of the EHMT1 gene, which is the fundamental cause of Kleefstra syndrome. However, the team never loses sight of any potentially quicker wins, such as determining if existing drugs can be repurposed to improve some Kleefstra Syndrome symptoms.
“We know what the break is, and where it is. It’s one switch that needs to be changed. The rest of the cell, we think the rest of the nerve is fine, there’s nothing fundamentally wrong with it except the faulty EHMT1 gene. So, I genuinely believe if we can correct this EHMT1 switch, those nerves have the potential to improve. Being the pragmatic scientist, I think the younger you can do it, the less delay, the greater the chance to catch up, but I also do think everyone could potentially benefit. We already know from other diseases, including those affecting the brain, that the human body has an amazing capacity to adapt, compensate and recover with ever-improving medical treatments.”
So, how soon might we hope for a therapy to compensate for the faulty EHMT1 gene?
“It’s not next week or next month, but we’re learning from other diseases that are going down the same path, and the science is progressing,” said Paul. “Another promising technology is called antisense oligonucleotide (ASO) which may provide a way to increase the output from the ‘good’ EHMT1 gene even if the faulty copy is still present. Science moves so rapidly, the technologies I have in my lab, were unimaginable just a few years ago.
Needless to say, the SAB is working with urgency. Edward is now four-years-old and still struggles eating solid foods.
However, thanks to the tireless efforts of Valeriya and his numerous therapists, Edward is physically strong, recently began speaking in three-word sentences, and loves playing with his younger brothers, Christian, 3, and Anthony, 1.
“Despite all the challenges, Edward never quits, it is humbling to witness. I am so proud to be his dad.”