Pipeline Conference - Ketogenic Compounds of the Treatment of Epilepsy

1. Ketogenic Compounds for the
Treatment of Epilepsy
Dominic P. D’Agostino, PhD
Assistant Professor
Hyperbaric Biomedical Research Lab
University of South Florida Morsani College of Medicine

2. Glucose
Insulin
Ketogenic Diet
Body Fat
Ketones
(energy!)
Difficult to sustain…

3. Ketones
(energy!)
Ketone Mineral Salts and Esters
Therapeutic Ketosis (KD)
BHB
AcAc
D’Agostino, D.P., et.al . AJP Regulatory, Integrative and Comparative
Physiology, 2013 May 15;304(10):R829-36.

4. ↓ Glucose
↑ BHB
↑ Acetone
(Metron)
↑ AcAc
Ketone Supplementation
Single Administration
Rapid Ketosis (30-60 minutes) Sustained Ketosis (>8 hrs)
Kesl SL, et al. Methods of sustaining dietary
ketosis in Sprague-Dawley rats. FASEB Journal
(2014) vol. 28 no. 1 Supplement 643.5

5. 575 %
Seizure
Resistance
Ketone
Ester
Ongoing testing in 4 seizure models
Physiological Resilience
Cognitive Performance
Physical Performance
Special Ops Diving

6. Antiseizure Mechanism(s)?
Adapted from: Kristopher Bough and Jong Rho. Anticonvulsant
Mechanism of the Ketogenic Diet. Epilepsia, 48 (1): 43-58, 2007.
Elevated Ketones Lowered Glucose
Ketogenic Diet, Ketone Esters
Serum + Hippocampal
Ketones (BHB, AcAc)
Adenosine
GABA/Glutamate
TCA Cycle
Intermediates
Glucose
Insulin
ROS
Oxidative
Stress

7. Summary
• Ketone supplementation produce fasting-
level ketosis without dietary restriction
• Therapeutic ketosis with ketone
supplementation delays seizures
• Multiple antiseizure mechanisms
• Pending FDA approval
• Phase 1 Pilot Study within 1 year
Questions?