The Alex Manfull Fund Supports Groundbreaking Research on PANS and PANDAS

The Alex Manfull Fund, established in memory of Alexandra “Alex” Manfull, who passed away at 26 due to untreated PANDAS, has awarded grants to three researchers aiming to advance understanding and treatment of PANS and PANDAS, a group of neuroimmune disorders that can strike young people after common infections.

Dr. Herbert Lachman, a researcher at a leading institution, will use the grant to study the role of pathogenic variants in DUOX2, a gene that helps the gut control bacteria, maintain the intestinal barrier, and communicate with the immune system. DUOX2 has been linked to gut dysbiosis and inflammatory bowel disease, conditions often seen in children with autism and other neurodevelopmental disorders.

Lachman hypothesizes that this gene variant could be connected to gut microbiome homeostasis and gut permeability, ultimately contributing to neuroinflammation. To test this hypothesis, his team will create human gut organoids, small, laboratory-grown models of the intestine, that carry the rare DUOX2 variant found in affected patients. The researchers will study intestinal permeability by comparing these variants with normal control organoids, examining both groups with and without exposure to immune cytokines. An increase in permeability would support the idea that immune cytokines and bacterial immune stimulators can penetrate the gut and activate the gut/immune/brain axis.

Another grant supports Dr. Sean Miller’s cutting-edge study, which will compare brain tissue from individuals who have succumbed to PANDAS with human brain organoids, small lab-grown models of developing brain tissue, that have been exposed to the blood serum of PANDAS patients. The study will identify changes in the organoids’ immune activity, brain cell communication, and synaptic function. To the best of the researcher's knowledge, these will be the first-ever human cortical models infused with PANDAS patient sera and compared directly to human brain transcriptome data.

A third grant supports Dr. Breithaupt’s work, building on findings from her previous TAMF-funded research. That work identified changes in two proteins, VEGFA and HGF, in young people with PANS and PANDAS. Because both proteins help regulate the blood-brain barrier and the brain’s blood vessels, the findings raised the question of whether inflammation elsewhere in the body could be leaving detectable changes in the barriers that protect the brain.

Dr. Breithaupt’s new study will focus on the choroid plexus, a highly vascular structure in the brain that helps form the barrier between the bloodstream and cerebrospinal fluid and plays an important role in communication between the immune system and the brain. Enlargement of the choroid plexus has been associated with neuroinflammation in a range of neurological and psychiatric disorders, but it has never been studied in PANS/PANDAS.

To investigate, her team will use structural MRIs from 47 young people with PANS/PANDAS and healthy controls to measure and compare the choroid plexus. The researchers hope to determine whether differences provide new clues to the role of inflammation in PANS/PANDAS.

Supporting this type of groundbreaking research is at the heart of the mission of The Alex Manfull Fund.