2017 Research Grant Recipients
C7 and the Ketogenic Diet
Juan M. Pascual, MD, PhD
Associate Professor
Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases
Department of Neurology & Neurotherapeutics, Eugene McDermott Center for Human Growth and Development, Pediatrics, Physiology
Rare Brain Disorders Program Director
UT Southwestern Medical Center
Dallas, Texas
Award Amount: $50,000 extension
We have used triheptanoin (C7) oil to treat Glut1 deficiency syndrome (Pascual et al. JAMA Neurol. 2014, 71:1255-65) in patients receiving a regular diet, who had no major side effects other than sporadic gastrointestinal intolerance. We will now investigate whether C7 can also be added to the ketogenic diet by simply replacing some of the ketogenic diet fat.
We want to test the compatibility of C7 with the ketogenic diet in patients who are prone to seizures (before or after the diet was initiated). The ultimate goal is to develop C7 as a safe complementary therapy to the ketogenic diet. The specific notion tested is that laboratory evidence that C7 may interfere with the ketogenic diet by inducing the formation of glucose in the liver, which is released into the bloodstream, potentially blocking ketosis.
Juan M. Pascual, MD, PhD
Associate Professor
Once Upon a Time Foundation Professorship in Pediatric Neurologic Diseases
Department of Neurology & Neurotherapeutics, Eugene McDermott Center for Human Growth and Development, Pediatrics, Physiology
Rare Brain Disorders Program Director
UT Southwestern Medical Center
Dallas, Texas
Award Amount: $50,000 extension
We have used triheptanoin (C7) oil to treat Glut1 deficiency syndrome (Pascual et al. JAMA Neurol. 2014, 71:1255-65) in patients receiving a regular diet, who had no major side effects other than sporadic gastrointestinal intolerance. We will now investigate whether C7 can also be added to the ketogenic diet by simply replacing some of the ketogenic diet fat.
We want to test the compatibility of C7 with the ketogenic diet in patients who are prone to seizures (before or after the diet was initiated). The ultimate goal is to develop C7 as a safe complementary therapy to the ketogenic diet. The specific notion tested is that laboratory evidence that C7 may interfere with the ketogenic diet by inducing the formation of glucose in the liver, which is released into the bloodstream, potentially blocking ketosis.
Testing the Efficacy of Ketone Supplementation in Glucose Transporter Type 1 Deficiency Syndrome (GLUT1 DS) Mice
Dominic D’Agostino, PhD
Associate Professor
Department of Molecular Pharmacology and Physiology
University of South Florida
Morsani College of Medicine
Tampa, Florida
Award Amount: $30,000 extension
Nutritional ketosis is well established as a neuroprotective metabolic therapy. Ketone bodies beta-hydroxybutyrate and acetoacetate provide an alternative fuel that helps protect the brain during limited glucose availability. Nutritional ketosis has profound anti-seizure properties in multiple animal models. Ketone supplementation can circumvent the dietary restriction that often limits the compliance and therapeutic efficacy of the ketogenic diet. The development and testing of ketone supplementation has tremendous therapeutic potential for those with GLUT1 DS.
Our laboratory continues to assess the efficacy and safety of ketone supplementation with the goal of getting this therapy to patients as fast as possible.
1) Establish and maintain GLUT1 DS mouse breeding colony at USF Vivarium (Completed with active IACUC protocol).
2) Assess behavioral and histological effects of ketone esters (BHB and AcAc) on mouse model of GLUT1 DS (Ongoing).
3) Assess behavioral and histological effects of ketone mineral salts on mouse model of GLUT1 DS (Ongoing).
4) Dose response and combined ketone formulation studies.
5) Biochemical and histological analysis of blood and tissues.
Dominic D’Agostino, PhD
Associate Professor
Department of Molecular Pharmacology and Physiology
University of South Florida
Morsani College of Medicine
Tampa, Florida
Award Amount: $30,000 extension
Nutritional ketosis is well established as a neuroprotective metabolic therapy. Ketone bodies beta-hydroxybutyrate and acetoacetate provide an alternative fuel that helps protect the brain during limited glucose availability. Nutritional ketosis has profound anti-seizure properties in multiple animal models. Ketone supplementation can circumvent the dietary restriction that often limits the compliance and therapeutic efficacy of the ketogenic diet. The development and testing of ketone supplementation has tremendous therapeutic potential for those with GLUT1 DS.
Our laboratory continues to assess the efficacy and safety of ketone supplementation with the goal of getting this therapy to patients as fast as possible.
1) Establish and maintain GLUT1 DS mouse breeding colony at USF Vivarium (Completed with active IACUC protocol).
2) Assess behavioral and histological effects of ketone esters (BHB and AcAc) on mouse model of GLUT1 DS (Ongoing).
3) Assess behavioral and histological effects of ketone mineral salts on mouse model of GLUT1 DS (Ongoing).
4) Dose response and combined ketone formulation studies.
5) Biochemical and histological analysis of blood and tissues.
