For more than three decades, FRAXA Research Foundation has worked to advance treatments for Fragile X syndrome. One of the most promising potential treatments today is BK (Big Potassium) channel openers. Many years of FRAXA-funded research have led to breakthroughs with this approach on two different fronts.
The Science Behind BK Channels
Fragile X syndrome occurs when an essential protein, FMRP, is absent.
Imagine a busy intersection full of cars with no brakes; turmoil and damage are inevitable. The same is true for the brain without FMRP; mRNAs travel through cells unchecked, haphazardly producing protein. This unregulated environment creates chaos in the brain and contributes to the cognitive and behavioral symptoms seen in Fragile X syndrome.
Lynne E. Maquat, PhD
FRAXA Investigator and Director of the Center for RNA Biology
University of Rochester, Rochester, NY
Excerpted from an article by the University of Rochester Medical Center: Fragile X Syndrome: What Happens in the Brain.
FMRP normally helps regulate BK channels, large ion channels in the membrane of axons, which act like natural “brakes” on overactive neurons. Without FMRP, BK channels don’t function properly. Opening these channels pharmacologically restores balance, addressing not just symptoms, but core brain dysfunction.
FRAXA’s Early Investments, from Basic Research to Clinical trials
The path to today’s clinical trials began with FRAXA Investigator Dr. Pete Vanderklish at Scripps Research Institute, who found that BK channels were underexpressed in Fragile X. FRAXA then funded French researchers Dr. Sylvain Briault and Dr. Jacques Pichon at the University of Orleans who were studying the BK channel as a potential cause of autism. Further FRAXA grants to Dr. Leonard Kaczmarek at Yale and Dr. Vitaly Klyachko at Washington University confirmed BK channels as a therapeutic target for Fragile X.
Much of this work was directed behind the scenes by Dr. Michael Tranfaglia, FRAXA’s Medical Director, who was steering BK channel openers through rigorous validation to attract pharmaceutical partners. BK channel openers went on to be tested successfully at the Drug Validation Initiative (FRAXA-DVI).
Clinical Readiness and Industry Momentum
BK channel openers have now advanced into formal drug development pipelines:
Spinogenix’s SPG601
Spinogenix’s SPG601 showed promising results in a Phase 2a trial in Fragile X syndrome conducted by Dr. Craig Erickson, Director of the Cincinnati Fragile X Research and Treatment Center. Spinogenix is now preparing to launch a Phase 2B/3 clinical trial of this BK channel opener in Fragile X syndrome.
Kaerus Bioscience’s KER-0193
Kaerus Bioscience’s KER-0193 completed Phase 1 with excellent safety and CNS engagement, earning FDA orphan and rare pediatric disease designations. Now Servier Pharmaceuticals has licensed global rights to Kaerus’ Fragile X program in a deal worth up to $450 million. The next step is Phase 2 trials in the US and Europe.
From Seed Funding to a Global Pipeline
What began with small FRAXA grants in France and the US has now blossomed into major pharmaceutical investment and imminent Phase 2/3 clinical trials. This journey from early research to clinical readiness with big pharma behind it demonstrates how each dollar given to FRAXA can spark research that grows exponentially, multiplying its impact on the path to treatments for Fragile X syndrome.
