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RESEARCH

RESEARCH FUNDING

The current grant cycle is CLOSED for the TESS Research Foundation Grant for research on SLC13A5 Deficiency, a Citrate Transporter Disorder. Stay tuned for future grant opportunities!

To see details on our 2018-2019 application guidelines, click HERE.

For any inquiries related to TESS Research Foundation Grant Program, Contact Kim Nye: kim@tessfoundation.org.

Meet Our Grant Recipients

TESS Research Foundation is excited to announce the recipients of the foundation’s 2018-2019 research grants.

“Last year TESS funded leading basic scientists to develop tools for better understanding SLC13A5.  This year we’re still funding leading scientists from around the world, but these scientists are using those tools to develop a cure,” said Matthew Bainbridge, PhD, TESS Research Foundation Scientific Advisory Board Member.  “TESS has taken a two-pronged attack on SLC13A5 deficiency.  The first, to identify pharmaceutical interventions that can correct or by-pass SLC13A5 function and the second, to completely replace SLC13A5 with a fully functional version with gene therapy. These two methods are using cutting edge technology and represent the best hope for the kids and families who suffer from this disease,” said Bainbridge.

Grants in total $560,000 have been awarded since we started TESS Research Foundation in 2015. The projects we have funded are listed below.

We are grateful to our donors who helped to make these grants possible, moving critical research about SLC13A5 Deficiency forward. With your continued support, we are working towards a healthier future for children suffering from SLC13A5 Deficiency.

TESS Foundation Funded Research Projects

2018-2019

SLC13A5 Patient-derived Cellular Models for the Identification of Biomarkers and Drug Screening Strategies.

Gaia Novarino, PhD

Institute of Science and Technology Austria

We will develop cell culture models based on SLC13A5 patient-derived induced pluripotent stem cells that recapitulate disorder pathophysiology. These models are particularly suited to address early developmental brain pathologies. Combining single-cell transcriptomics, cellular and network electrophysiology as well as morphology we will identify pathophysiological changes between control and patient-derived cell culture models that will help understanding pathology mechanisms and identify biomarkers. Experiments for biomarker identification will be designed to allow straightforward application for medium to high-throughput drug and genetic screening assays. We believe this approach will identify SCL13A5 disorder pathology relevant biomarkers and disorder mechanisms which will be directly applicable to search for pharmacological treatments.

Screening small molecules for the activation of NaCT mutants in SLC13A5 Deficiency.

Da-Neng Wang, PhD
NYU School of Medicine

SLC13A5 Deficiency is caused by mutations in the SLC13A5 gene. This gene encodes a sodium-driven citrate transport protein named NaCT. Disease-causing mutations abolish the uptake of citrate in neurons of the brain. We plan to develop a simple and efficient screening platform to search for small molecule activators that can rescue the mutants’ citrate transport activity.

Gene Therapy for SLC13A5 Deficiency.

Rachel Bailey, PhD
UT Southwestern Medical Center

Current treatment for SLC13A5 deficiency is limited to symptomatic palliative care and there remains an urgent need for an effective treatment that targets the cause of the disease. Gene therapy is one of the emerging strategies for the treatment of inherited disorders like SLC13A5 deficiency by delivering therapeutic genes directly to a patient’s cells in place of drugs or surgery. The proposed research will test a gene therapy approach in mice with SLC13A5 deficiency. A very similar gene therapy approach is currently being tested in humans with Giant Axonal Neuropathy. Results from the studies under this proposal could eventually allow the translation of this approach into a human treatment.

2017

The Na+/Citrate Transporter In Human Neurons.

Anne Murphy, PhD and Ana M. Pajor, PhD

University of California San Diego

In this project, Dr. Pajor, Dr. Murphy and their teams will investigate the effect of loss of SLC13A5 expression on transport of citrate and succinate in cultured human neurons. They plan to study the metabolic and bioenergetic consequences of this loss to understand how it results in the development of epilepsy.

Drug Discovery in Slc13a5 Mutant Zebrafish.

Deborah M. Kurrasch, PhD
University of Calgary

Over the past funding period, Dr. Kurrasch and her team developed a zebrafish model that harbors a frameshift mutation in slc13a5. In the proposed project, she will continue testing this zebrafish model to screen a new repurposed drug library and further validate the drugs uncovered in these screens.

Creation Of Humanized Mouse And Fly Models Of SLC13A5 Mutant Syndrome To Determine The Cause Of Neurological Dysfunction And To Identify And Test Treatments.

Stephen L. Helfand, MD
Brown University

In this project, Dr. Helfand and his collaborators aim to create a humanized mouse model in which a normal mouse SLC13A5 gene will be replaced by either a normal human SLC13A5 gene or a mutant human SLC13A5 gene. Dr Helfand has also created fly models of SLC13A5 and aims to study them further to pinpoint the physiological pathway that is affected due to SLC13A5 mutation. These mice and fly models will be instrumental in understanding how human SLC13A5 mutations cause neurological deficits and will be used to test and validate proposed treatments.

2015-2016

The Pajor Lab.

The main focus of the Pajor Lab is to understand the mechanism of sodium-coupled transporters, particularly the Na+/dicarboxylate cotransporters (NaDC) from the SLC13 family. A number of mutations have been identified in the NaCT transporter gene (SLC13A5) in patients with epileptic encephalography. The Pajor Lab explores what these mutations do to the function of NaCT. By studying the effects of these mutations, we may be able to identify a treatment for this disease.

SLC13A5 Bio-Bank at Stanford.

This project, spearheaded by Dr. Brenda Porter, creates a Bio-Bank of blood and skin samples of SLC13A5 patients and their parents. These blood and skin samples will be made available to researchers studying SLC13A5 and its role in epilepsy. Currently there are no animal models that recapitulate the neurological phenotype of SLC13A5. Ideally, the mechanisms underlying SLC13A5 mutations need to be studied in human patients and in their cells. Since neurons maintain the genetic profile of an individual, studying neurons derived from human induced pluripotent stem cells (hiPSC) is attractive as a method for studying neurons from SLC13A5 patients. A Bio-Bank is the first step in creating hiPSC and neuronal cell lines.

Baylor College of Medicine and Texas Children’s Hospital.

Dr. Brett Graham and Dr. Sarah Elsea are collaborating to screen and monitor metabolomic markers for SLC13A5 Deficiency and translate them into precision medicine.  They have currently enrolled several patients with SLC13A5 mutations in a Triheptanoin drug trial.  Triheptanoin, made by Ultragenyx, is intended to provide patients with medium-length, odd-chain fatty acids. Due to its odd-chain properties, triheptanoin is broken down into metabolites that replace deficient intermediates in the Citric Acid Cycle, a key energy-generating process that is likely disrupted by SLC13A5 mutations.

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