Unlocking Brain Health: Targeting Mitochondrial Function in Neuropsychiatric Disorders

Pioneering Research Uncovers Link Between Blood-Brain Barrier and Neuropsychiatric Disease in 22qDS

In a recent collaborative endeavor, scientists from the University of Pennsylvania School of Veterinary Medicine and the Children's Hospital of Philadelphia have unearthed a critical relationship between impaired mitochondrial function within the blood-brain barrier (BBB) and the development of neuropsychiatric disorders in certain individuals with 22qDS. Their findings also point to the exciting possibility of utilizing existing cholesterol medications to mitigate this dysfunction.

The Blood-Brain Barrier: A Vital Protector and Its Vulnerability

The blood-brain barrier acts as the brain's exclusive defense system, meticulously regulating the passage of substances from the bloodstream into the central nervous system. Its integrity is paramount for optimal neurological performance. Disturbances within this barrier have been implicated in a spectrum of neurological ailments, ranging from developmental disorders like autism to neurodegenerative conditions such as Alzheimer's disease.

Mitochondria's Crucial Role in BBB Function and 22qDS Implications

The BBB is notably rich in mitochondria, the cellular powerhouses. While mitochondrial impairments have been linked to various neurological conditions, their specific contribution to BBB dysfunction remained largely unexplored until now. Researchers focused on 22qDS (DiGeorge syndrome), a genetic disorder known to elevate the risk of neurodevelopmental and neurodegenerative diseases, with a high propensity for psychosis and schizophrenia among affected individuals. This condition provided a unique lens through which to examine the broader implications of mitochondrial health on brain function.

A Collaborative Breakthrough: Bridging Expertise for Deeper Understanding

With Children's Hospital of Philadelphia hosting the world's largest clinic for 22qDS, and researchers at Penn and CHOP deeply committed to studying this complex condition, a powerful synergy was formed. Dr. Jorge Iván Alvarez from Penn Vet and Dr. Stewart A. Anderson from CHOP emphasized the strength of their combined expertise. Their collaborative efforts confirmed previous suspicions that the BBB is indeed compromised in 22qDS, suggesting a disruption in the intricate communication pathways between the brain and the body.

Promising Therapeutic Avenues: Repurposing Existing Medications

The study yielded particularly encouraging results regarding a potential therapeutic approach. Researchers observed a "leaky" BBB in both human induced pluripotent stem cell-derived brain microvascular endothelial cells from 22qDS patients and in preclinical models of the syndrome. Remarkably, treatment with bezafibrate, a cholesterol-lowering drug known to activate mitochondrial generation and turnover, significantly improved BBB function in both experimental setups. Furthermore, this treatment also rectified social memory deficits in the preclinical models, a common issue associated with BBB dysfunction and schizophrenia. These findings suggest that drugs in this class could be repurposed, offering a novel treatment strategy for 22qDS. While the study centered on 22qDS, the implications extend to other neuropsychiatric disorders where mitochondrial dysfunction in the BBB may play a contributing role, including other forms of psychosis.