Research Brings Us Closer Every Day
Understanding the Disease
- Dr. Raghu Padinjat (Disease Biology & Therapeutic Discovery)
Developing New Therapies
- Dr. Jennifer Gallop (Drug Repurposing)
- Dr. Claudio Aguilar (Drug Repurposing)
- Dr. Antonella De Matteis (Novel Therapeutics)
Testing Therapies in Patients
- Dr. Francesco Emma (Clinical Translation)
Transformative Treatments
- Cure Lowe Foundation (Gene Replacement Therapy)
Dr. Raghu Padinjat
Research Focus: Disease Biology & Therapeutic Discovery
Dr. Raghu Padinjat, a researcher at the National Centre for Biological Sciences (Bengaluru, India), is an internationally recognized expert in phosphoinositide biology—the cellular signaling system directly disrupted by OCRL mutations.
His research has helped define how abnormal phosphoinositide metabolism alters lipid signaling, drives the accumulation of PI(4,5)P₂, and contributes to neurological dysfunction in Lowe syndrome. Building on these discoveries, research from his broader scientific program has demonstrated that correcting these lipid imbalances can improve neuronal function in preclinical Lowe syndrome models using a drug repurposing approach.
His work continues to provide important insights into the biology of Lowe syndrome while identifying new therapeutic pathways for future treatment development.
Dr. Jennifer Gallop
Research Focus: Drug Repurposing
Dr. Jennifer Gallop, a researcher at the Gurdon Institute, University of Cambridge (United Kingdom), has led one of the most promising examples of drug repurposing for OCRL-related disease. Her research has focused on understanding how OCRL deficiency disrupts phosphoinositide signaling, actin organization, and kidney proximal tubule function.
Working in collaboration with Professor Olivier Devuyst’s group, Dr. Gallop identified alpelisib, an FDA-approved PI3K inhibitor, as a promising repurposed therapy. In preclinical studies, alpelisib restored actin organization, improved proximal tubule function, reduced proteinuria, and rescued megalin expression in mouse models of Lowe syndrome and Dent disease type 2.
This work provided the scientific foundation for the ALPEDENT clinical trial, demonstrating how laboratory discoveries can advance from preclinical research into human studies and potentially accelerate the development of targeted therapies for OCRL-related disease.
Dr. Claudio Aguilar
Research Focus: Drug Repurposing
Dr. Claudio Aguilar, a researcher at Purdue University (West Lafayette, Indiana, USA), has focused on identifying the cellular pathways disrupted by OCRL deficiency and determining whether existing FDA-approved medications can restore normal cellular function.
His research identified abnormalities in the mTOR and Rho GTPase signaling pathways and demonstrated that drugs such as rapamycin and statins can improve specific cellular defects in preclinical models. His work also suggests that combination therapies may ultimately be needed because OCRL deficiency affects multiple biological pathways simultaneously.
By identifying existing medications that target these pathways, Dr. Aguilar’s research continues to expand the pipeline of potential therapies that may advance more rapidly than newly developed drugs.
Dr. Antonella De Matteis
Research Focus: Novel Therapeutics
Dr. Antonella De Matteis, a researcher at the Institute of Genetics and Biophysics, National Research Council (Naples, Italy), has spent many years investigating the cellular mechanisms underlying Lowe syndrome.
Her research identified defects in adenosine signaling as a potential therapeutic target and ultimately led to the discovery of Piclodenoson (formerly CF101) as a promising drug candidate. Through a licensing agreement with Can-Fite BioPharma, Piclodenoson has advanced as a potential treatment for Lowe syndrome based on its ability to improve cellular function and reduce disease-related abnormalities in preclinical models.
This work illustrates how fundamental discoveries in disease biology can lead to the development of entirely new therapeutic approaches for Lowe syndrome.
Dr. Francesco Emma
Research Focus: Clinical Translation
Dr. Francesco Emma, a pediatric nephrologist at Bambino Gesù Children’s Hospital (Rome, Italy), is leading the ALPEDENT clinical trial—the first study to evaluate alpelisib as a potential treatment for an OCRL-related disease.
Building on years of laboratory research, the trial is investigating whether alpelisib can improve kidney tubular function and reduce protein loss in adults with Dent disease type 2 caused by OCRL mutations. If successful, the study could provide the first clinical evidence supporting a targeted treatment for OCRL-related kidney disease and lay the groundwork for future studies involving children and individuals living with Lowe syndrome.
This important work represents a critical step in moving promising laboratory discoveries into clinical trials for patients.
Cure Lowe Foundation
Research Focus: Gene Replacement Therapy
The Cure Lowe Foundation, based in Copenhagen, Denmark, was founded by Sebastian Honoré following his son Walther’s diagnosis with Lowe syndrome to accelerate the development of a gene therapy for the disease.
Working with Dr. Leopoldo Staiano and an experienced international gene therapy team, the Foundation is advancing a program designed to deliver a functional copy of the OCRL gene directly to kidney cells. The therapy has demonstrated encouraging preclinical results in patient-derived kidney cells, human kidney organoids, and non-human primate studies, and is progressing toward orphan drug designation and future clinical trials.
Recognizing the importance of strong preclinical models, the Lowe Syndrome Association has joined global partners, including the Lowe Syndrome Trust and the Cure Lowe Foundation, in supporting the rederivation of healthy OCRL mouse colonies. Maintaining these critical research models helps ensure investigators around the world have reliable tools to accelerate both therapeutic development and future gene therapy research.