Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin

Inclusion Criteria:

• Diagnosis of Classic Rett syndrome as defined by the clinical consensus criteria

• Presence of a MECP2 mutation

• Post-regression stage of development, defined as greater than 6 months since the lastloss of hand use or verbal language

• Average of at least 4 observable seizures (generalized or partial-onset [GeneralizedTonic-Clonic, Generalized Tonic, Generalized Clonic, Generalized Atonic, Partial/Focalwith Secondary Generalization, Myoclonic, Myoclonic Atonic, Myoclonic Tonic, ComplexPartial/Focal, and Simple Partial/Focal Motor) in one month prior to the study bycaregiver report or presence of dystonia on average at least four times in one monthprior to the study in at least one body region rated as at least "mild" by caregiverreport

• Use of at least one anti-seizure medication at screening visit

• At screening visit, managed on four or fewer concomitant anti-seizure medications thatmust have been stable in dose at least one month prior to the beginning of screeningand anticipated to remain stable in dose through the end of the 8.5 month trial period

• Legally authorized caregiver must be willing to give written informed consent afterthe nature of the study has been explained, and prior to any research-relatedprocedures

• Caregiver and participant must, in the opinion of the investigator, be willing andable to complete all aspects of the study, comply with accurate completion of theseizure and dystonia diaries, and be likely to complete the four month treatmentperiod

Exclusion Criteria:

• Markedly abnormal metabolic screening laboratory testing (e.g., serum alanineaminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2X theupper limit of normal)

• Any known hypersensitivity to triheptanoin that, in the judgment of the investigator,places the subject at increased risk for adverse effects

• Prior use of triheptanoin within 1 month prior to screening

• Participants or caregivers who are unwilling or unable to discontinue use of aprohibited medication or other substance that may confound study objectives

• Use of any other investigational product, including drugs or supplements within 1month prior to Screening, or at any time during the study

• Has a condition of such severity and acuity, in the opinion of the investigator, thatit warrants immediate surgical intervention or other treatment

• Has a concurrent disease or condition, or laboratory abnormality that, in the view ofthe investigator, places the subject at high risk of poor treatment compliance or ofnot completing the study, or would interfere with study participation or introducesadditional safety concerns (e.g., diabetes mellitus)

• Pregnant or nursing women