Kleefstra Syndrome Drug Development Research Fund

In 2015, K.I.D.S. IQ Project began raising money to fund scientific research projects aimed at advancing a drug treatment for Kleefstra Syndrome (KS). With the help of our partner organization, GlobalGiving Foundation, we made great progress toward our funding target and have now raised approximately C$700,000 globally. Based on recommendations of our Scientific Advisory Board (SAB), K.I.D.S. IQ Project made the decision to immediately begin the process to deploy some of these funds on two specific research projects.

The first project formally began in December 2016 and is being led by Dr. Hans van Bokhoven and Dr. Nael Nadif Kasri, both of Radboud University (The Netherlands), in collaboration with Dr. Hans Bjornsson of Johns Hopkins University in the United States. The leaders of this research team will assemble and screen a short list of chemical compounds, leveraging those that have historically been able to target syndromes and diseases that are similar to Kleefstra Syndrome (or those that may be best suited to tackle what is already known about the biology of Kleefstra Syndrome itself). How exactly will this screen work? The Radboud team has developed Kleefstra Syndrome neurons (brain cells) in a lab, with these neurons having been derived from a patient’s skin sample through a process involving induced pluripotent stem cell (iPSC) technology (iPSCs are a relatively new technology that enable neurons to be derived from disease patients). These disease-state neurons have been evaluated for deficiencies as compared to normal neurons, and the team will be able to test the impact of chemical compounds in terms of their ability to improve noted deficiencies. After an initial screen of the compounds, the team will advance the top candidates (which produce the most significant improvements) to test in Kleefstra Syndrome mice. Mice are an important part of the testing as they provide are a read on behavioral and intellectual changes. This project is expected to last up to three years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

The second project is being led by Dr. Carl Ernst of McGill University in Canada. Dr. Ernst will create neuronal or similar cells from a Kleefstra Syndrome patient’s skin sample that can be used as a screening tool for chemical compounds, also leveraging iPSC technology. The tool will screen for drugs that specifically increase the production of the key protein (EHMT1) implicated in Kleefstra Syndrome, as this protein is not produced in sufficient quantity in Kleefstra Syndrome patients. Why might this overall approach work? Kleefstra Syndrome patients have two copies of EHMT1 (just like the normal human population), with one copy functioning normally and the other being deficient (that deficiency is caused by the patient’s deletion or mutation). In working to identify drugs that can successfully interact with and stimulate increased production of the healthy copy of EHMT1, we may be able to compensate for the lack of EHMT1 production stemming from the unhealthy copy. This overall approach, known as “upregulation”, has proven successful in other diseases where one copy of the mutated/deleted gene was originally not producing in sufficient quantity. Dr. Ernst will begin his work screening FDA-approved drugs and, given these drugs have already passed many hurdles, any early successes could result in tremendous time and cost savings. This project is expected to last up to two years, with a goal of identifying a potential drug candidate for testing on human Kleefstra Syndrome patients.

Our progress to date would not be possible without our donors. We expect that those funds raised specifically through GlobalGiving Foundation will be applied (during the course of 2017) to the initial phases of one or both of the projects described above. Once again, we thank you for your continued support!

Links:

• https://www.kidsIQproject.org