Sirolimus for Leigh Syndrome

Exclusion Criteria

• •1. Cardiac ejection fraction ≤ 50 %, shortening fraction ≤ 25% on cardiac echocardiogram within one year of screening and/or severe end-organ hypo-perfusion syndrome (secondary to cardiac failure) resulting in lactic acidosis.
• •2. Patients with implanted cardiac assist/medical devices (including pacemakers), unless device was implanted prophylactically, and the patient is clinically asymptomatic.
• •3. In the opinion of the investigator, clinically significant ECG and/or echocardiogram alterations at the time of screening.
• •4. Myocardial infarction within 6 months prior to enrollment.
• •5. Symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or unstable coronary artery disease.
• •6. Prior history of hypersensitivity to sirolimus or other mTOR (Mechanistic Target of Rapamycin inhibitors).
• •7. Prior history of angioedema requiring treatment or cessation of a presumed causative agent.
• •8. Planned surgical procedure during the study period.
• •9. Confirmed or highly suspected immunodeficiency disorder(s), including but not limited to, common variable immune deficiency (CVID), complement deficiency, etc.
• •10. Clinically significant proteinuria that requires ongoing medical therapy.
• •11. Any uncontrolled psychiatric or medical condition which, in the opinion of the investigator, would interfere with the patient's participation in the study.
• •12. Patients who are breastfeeding or are pregnant.
• •13. History of solid organ transplant (kidney, liver, heart, lung) or bone marrow transplant.
• •14. Treatment with any investigational drug (i.e., a drug for which there is no approved indication), including an investigational drug for mitochondrial disease within 1 month prior to receiving the first dose of study drug (or within 3 months for a trial with an investigational biologic).
• •15. Patients with confirmed or suspected increased intracranial pressure, pseudotumor cerebri (PTC)/idiopathic intracranial hypertension, and or papilledema.
• •16. Currently active malignancy (other than adequately treated non-melanoma skin cancers \[i.e., squamous cell and/or basal cell carcinoma\], carcinoma in situ of the cervix, or other adequately treated carcinoma in situ) and/or ongoing treatment for malignancy are ineligible. Patients are not considered to have a currently active malignancy if they have completed therapy and are free of disease for ≥ 1 year.
• •17. Recent infection requiring systemic anti-infective treatment that was completed ≤ 14 days prior to enrollment.
• •18. Uncontrolled diabetes mellitus, as defined by HbA1c \> 8%, despite adequate therapy.
• •19. History of interstitial lung disease and/or pneumonitis.
• •20. Use of strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4 (CYP3A4) and/or p-glycoprotein (p-GP) within the 14 days prior to receiving the first dose of study drug. Additionally, use of any known CYP3A4 substrates with a narrow therapeutic window (e.g., fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfenadine) within the 14 days prior to receiving the first dose of study drug.
• •21. Use of medications with a high risk of angioedema
• •22. Known human immunodeficiency virus (HIV), active hepatitis B or hepatitis C infection(s).