Mitochondrial Alteration
Conditions
Brief summary
The purpose of the study is to determine in vitro effects on mitochondrial function of selected chemical agents in human cells, and assess the capability of a cell-permeable succinate prodrug to attenuate toxic effects The project aims at repurposing this recent pharmaceutical discovery, currently being developed for treatment of toxic exposure, for an expanded indication to treat chemically induced mitochondrial toxicity.
Detailed description
The study duration per subject will be approximately 15 minutes to complete the one time blood collection.
Interventions
None listed
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Children's Hospital of Philadelphia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
Patient Inclusion Criteria: 1. Males or females age greater or equal 2 years of age 2. Weight greater or equal to 10 kg 3. Parental/guardian permission (informed consent) and if appropriate, child assent. Patient
Exclusion criteria
1. Known primary mitochondrial disorder. 2. Use of an investigational drug within 30 days prior to enrollment. 3. Parents/guardians or subjects who in the opinion of the Investigator, may be non-compliant with study schedules or procedures. Volunteer Inclusion Criteria 1. Males or females \> 18 years of age 2. Employee, trainee, or student informed consent Volunteer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Attenuation by the succinate prodrug of toxin-induced decrease in mitochondrial respiration. | by end of 2018 | Data will be assessed using 2-tailed Student's t-test. Dose-response curves for respiration will be made for each toxin and IC50 calculated. In case of difficulties in demonstrating acute toxicity of chemical agents, dose-titration experiments and long-term incubation (up to 24 hours) will be performed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Attenuation of toxin-induced decrease in mitochondrial membrane potential and attenuate lactate production by the succinate prodrug. | by end of 2018 | Data will be assessed using 2-tailed Student's t-test. Dose-response curves for respiration will be made for each toxin and IC50 calculated. In case of difficulties in demonstrating acute toxicity of chemical agents, dose-titration experiments and long-term incubation (up to 24 h) will be performed |
Countries
United States
Outcome results
None listed