Treatment of Mitochondrial Dysfunction in Rett Syndrome With Triheptanoin

The aim of this study is to evaluate the safety and tolerability of triheptanoin in
participants with Rett syndrome using laboratory values, electrocardiogram, rate of adverse
events (AE), and physical exam. This study also seeks to evaluate the efficacy of UX007
(triheptanoin) in improving overall seizure frequency, dystonia severity, and quality of
life. Participants who are eligible will take triheptanoin daily. Participation in the
primary arm of this study will last up to 8.5 months, with an optional 36 month extension.

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 last
loss of hand use or verbal language

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

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

- At screening visit, managed on four or fewer concomitant anti-seizure medications that
must have been stable in dose at least one month prior to the beginning of screening
and 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 after
the nature of the study has been explained, and prior to any research-related
procedures

- Caregiver and participant must, in the opinion of the investigator, be willing and
able to complete all aspects of the study, comply with accurate completion of the
seizure and dystonia diaries, and be likely to complete the four month treatment
period

Exclusion Criteria:

- Markedly abnormal metabolic screening laboratory testing (e.g., serum alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding 2X the
upper 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 a
prohibited medication or other substance that may confound study objectives

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

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

- Has a concurrent disease or condition, or laboratory abnormality that, in the view of
the investigator, places the subject at high risk of poor treatment compliance or of
not completing the study, or would interfere with study participation or introduces
additional safety concerns (e.g., diabetes mellitus)

- Pregnant or nursing women