The purpose of this study is to determine whether triheptanoin (UX007) is effective in the
treatment of neurological symptoms related to citrate transporter deficiency (SLC13A5 gene
This compassionate use research study has been developed to study an investigational drug,
triheptanoin (UX007), for the treatment of neurological symptoms related to citrate
transporter deficiency, a disease with no existing treatment. The hypothesis is that
triheptanoin will restore deficient energy metabolism in these patients, leading to improved
seizure control, mental clarity, and physical strength.
Based on the literature, the SLC13A5 gene product is a citrate transporter. However, there
is the possibility that other compounds are transported as well. The gene may be expressed
in human neurons and function at the level of the plasma membrane. The hypothesis is that
the transport of citrate across the plasma membrane from the extracellular space into the
cytoplasm plays a role in maintaining the pool size of citrate in both the cytoplasm and
mitochondrial matrix. Triheptanoin therapy may increase the metabolism of odd-chain fatty
acids in neuronal mitochondria and thereby increase the levels of succinyl-CoA, leading to
an increase in citrate concentrations. The increased level of citrate in the mitochondrial
matrix may lead to an increased efflux of citrate from the matrix to the cytoplasm, thus
increasing the cytoplasmic pool of citrate and allowing the malfunctioning citrate
transporter to be bypassed. If successful, triheptanoin treatment will improve neuronal
function and lead to an improvement in CNS function for patients.
While investigators will follow the course of subjects with considerable interest and may
use some of the collected data for clinical research, this study is done for humanitarian
- Diagnosis of citrate transporter deficiency due to mutations in the SLC13A5 gene.
- Presentation with severe global developmental delay and seizures.
- Valproate is an AED that partially inhibits the TCA cycle via alpha-ketoglutarate
dehydrogenase and should not be administered to subjects taking UX007.