Overview

Past mitochondrial disease treatment studies have been unsuccessful in determining treatment efficacy, and a major factor has been the lack of validated biomarkers in mitochondrial myopathy (MM). There is currently a growing number of potential new treatments to be tested through MM clinical intervention trials, which has created a pressing need for quantitative biomarkers that reliably reflect MM disease severity, progression, and therapeutic response. The purpose of the study is to measure the efficacy of an electrochemical oxygen nanosensor to measure in vivo mitochondrial function in human muscle tissue, and its ability to discriminate MM patients from healthy volunteers. The data and results from this nanosensor study may contribute to current and future research, including improved diagnostic and therapeutic approaches for patients with mitochondrial disease.

Eligibility

Inclusion Criteria:

• Inclusion Criteria for Healthy Controls
  1. Males and females, between the ages of 18 and 65 years, inclusive
  2. Provide informed consent for study participation; able to understand and complete the protocol
  3. Able to ambulate independently
  4. Able to perform bicycle ergometry

Inclusion Criteria for Mitochondrial Myopathy (MM) Cases

1. Males and females, between the ages of 18 and 65 years, inclusive
2. Provide informed consent for study participation; able to understand and complete the protocol
3. Genetically-confirmed MM as defined by a diagnosis of primary mitochondrial disease (PMD) with predominant symptoms of myopathy as expressed by exercise intolerance and muscle weakness and fatigue.
4. Previously enrolled (or will enroll) in Children's Hospital of Philadelphia (CHOP) Institutional Review Board (IRB) study #08-006177 (Falk, PI) or CHOP IRB #16-013364 (Zolkipli, PI)
5. Able to ambulate independently
6. Able to perform bicycle ergometry

Exclusion Criteria:

Subjects will be excluded if any of the following apply:

1. Unable to provide informed consent and complete all study procedures, including ergometry
2. Non-ambulatory or unable to ambulate independently
3. Pregnant
4. Within 1 month of a recent hospital admission due to acute illness
5. Have severe cardiac disease as defined by an ejection fraction of less than 35% and New York Heart Association Functional Classification Class III; or severe pulmonary disease as defined by the need for supplemental O2 therapy or daytime ventilatory support
6. Have a tracheostomy
7. Have a known bleeding disorder and/or family history (first-degree relative) with a known bleeding disorder
8. Daily intake of aspirin or any other anti-platelet therapy which cannot be temporarily discontinued for medical reasons
9. a) Have known or suspected congenital or acquired immune deficiency; b) concurrent use of immunosuppressive drugs, including corticosteroids; c) past history of recurrent (more than 6 times per year) severe (required hospitalization) skin or soft tissue infections; d) history of infection or delayed wound healing after surgery or biopsy; e) known history of neutropenia with absolute neutrophil count less than 500/mm3
10. Undergo chronic steroid treatment as defined by daily oral intake (for more than 1 month) or have existing untreated endocrinopathies, such as hypothyroidism that caused acquired myopathy
11. Prone to hypertrophic scars and keloids
12. Have any other known inherited myopathy, such as Duchenne muscular dystrophy or congenital myopathy
13. Known allergy to lidocaine
14. Have a cognitive impairment that may prevent the ability to complete study procedures
15. Unable to comply with the requirements of the study protocol and/or unsuitable for the study for any reason, in the opinion of the principal investigator
16. Individuals from vulnerable populations (e.g., prisoners/detainees)
17. Participants who are unable to speak and/or read English (as participants will be required to be proficient to complete study procedures)
18. Employed by the U.S. Department of Defense, including U.S. military personnel