Transgenerational Metabolic-Immune Biomarkers of Neurological and Neurodevelopmental Disorders

Southwest Autism Research & Resource Center

Status: Enrolling

Conditions: Psychiatric Disorder; Epilepsy; Autism Spectrum Disorder; Brain Tumor; Mitochondrial Pathology; Mitochondrial Diseases

Study type: Observational

Funder types: Other

Identifiers

NCT04322734

Mito Tissue

Details and patient eligibility

About

The study involves up to 5 visits for a fasting blood draw, behavioral assessments, and/or questionnaires. Other samples may be collected when appropriate.

This study is currently recruiting.

There is no cost for visits or study-related exams.

Full description

Mitochondria are essential for a wide range of functions in almost every cell in our body. Best known for their role in adenosine triphosphate (ATP) production, mitochondria are also closely involved in a wide variety of cell functions such as calcium buffering, redox regulation, apoptosis and inflammation, and regulate metabolism through several mechanisms, including epigenetic changes. ATP produced is essential for many cellular systems. Thus, abnormal mitochondrial function can adversely affect cellular systems by several mechanisms.

Given the important role of the mitochondria in cellular function, individuals with classic mitochondrial disease demonstrate devastating symptoms, particularly in tissues that have high-energy demands such as the brain, muscles, gastrointestinal (GI) tract and immune system. Mitochondrial dysfunction contributes to the pathophysiology of more common diseases, including psychiatric diseases, neurodegenerative disorders, neurological disorders including migraine and seizures, persistent systemic inflammation, cardiac disease, cancer and diabetes. Mitochondrial dysfunction also effects a significant portion of individuals with autism spectrum disorder (ASD) as well as genetic syndromes associated with ASD.

One of our goals is to develop a method using the Seahorse Analyzer to measure individual variations in mitochondrial function which can identify children with medical disorders and mitochondrial dysfunction without an invasive muscle biopsy. In order to establish comprehensive profiles of mitochondrial function for individuals with known neurological and neurodevelopmental disorders, we will compare blood, urine, and stool from these individuals to those of healthy, typically developing (TD) children. The relationship between mitochondrial function, development, and behavior will be assessed by performing standard developmental testing. In addition, in patients who have a procedure that produces leftover tissue, we will examine the mitochondrial function in that tissue and correlate it with findings from blood.

Enrollment: 500 estimated patients

Sex: All

Ages: Under 18 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (ASD):

1. ASD, as defined by either a gold standard measure for ASD diagnosis, the Autism Diagnostic Observation Schedule (ADOS); the Autism Diagnostic Interview-Revised (ADI-R); and/or a comprehensive assessment that is consistent with ASD, in the opinion of the principal investigator. For those the PI believes a prospective diagnosis of ASD is warranted, a formal diagnostic assessment will be scheduled at screening.
2. 0 years through 17 years 11 months of age

Inclusion Criteria (TD, MD, Epilepsy, Brain Tumor, Psychiatric)

1. 0 years to 17 years 11 months of age

Exclusion Criteria (All):

1. History of a significant adverse reaction to a prior blood draw
2. In females of reproductive age, pregnancy or plans to become pregnant
3. Any other historical event/information that may, in the opinion of the PI, be a reason to exclude the child from participation.

Trial design

500 participants in 9 patient groups

ASD (General)

Description:

150 children with ASD and unknown MD status

ASD (With MD)

Description:

50 children with ASD and confirmed MD

ASD (No MD)

Description:

50 children with ASD and ruled out MD

Epilepsy

Description:

50 children with epilepsy (primary) and no ASD

Brain Tumor

Description:

50 children with brain tumor (primary) and no ASD

Psychiatric Disorder

Description:

50 children with psychiatric disorder (primary) and no ASD, using lithium treatments

MD (No ASD)

Description:

50 children with MD (primary) and no ASD

TD (With ASD Sibling)

Description:

50 TD children with a sibling with ASD/neurodevelopmental delay

TD (No ASD Sibling)

Description:

50 TD children with no siblings with ASD/neurodevelopmental delay