PANDAS Network together with the Alex Manfull Memorial Fund are funding two new projects that will take place in 2020 with results to be published in 2021-2022.
Tonsil Microbiome
Dr. Earl Harley, ENT at Georgetown will collaborate with the Agalliu Lab on the analysis of tonsil tissues of 20 children with a strong streptococcous history. This study will be announced in Fall 2020 and will seek to find both immune markers and genetic factors. Both tissue and blood sera will be analyzed at the Columbia University, Agalliu Lab and Georgetown University Labs.
This will further identify the presence of key Th17 cells that impact PANDAS children. Cytokines/ chemokines in both tonsillar tissue and serum before and after tonsillectomy will be studied together with potential genetic markers such as RORγt discovered by Maryann Platt's, PhD candidate, Columbia Univ. It is suspected by earlier work by Dr. Agalliu, that human tonsils carry autoimmune cells that can
potentially adversely
impact healing of children.
To understand how tonsil and blood sera of PANDAS children alter healthy immune function -
Watch Three Videos:
Gut Microbiome & Autoantibody Identification
PN and The Alex Manfull Memorial Fund are very pleased to announce that they have agreed to fund two studies to be conducted by Pawel R. Kiela, DVM, PhD at the University of Arizona in the Department of Pediatrics, Division of Pediatrics Gastroenterology and Nutrition. These studies will further the knowledge of the relationship between the gut microbiome and PANDAS and, hopefully, move us closer to developing a new diagnostic tool based for PANDAS, based on autoantibody screening.
In the first part of Study I, Dr. Kiela will complete the metagenomics analysis of the gut microbiota (begun in an earlier study) to, hopefully, identify “a unique but persistent microbial signature among [PANDAS] children.”
In the second part of Study I, germ-free mice will be “humanized” with gut microbiota from either healthy or PANDAS cases. Then both groups will be given repeatedly immunized intranasally with
Streptococcus pyogenes
(GAS-2W) to assess the role of gut microbiota in
S. pyogenes
-induced neuroinflammation.
In the third part of Study I,
Akkermansia
municiphila
(one of the microbial species that most prominently decrease in PANDAS patients) will be orally administered to conventional mice that will be repeatedly immunized intranasally with
Streptococcus pyogenes
(GAS-2W) to induce neuroinflammation to observe whether
A. municiphila
can reduce or prevents the development of neuroinflammatory and behavioral symptoms.
In Study II, Dr. Kiela will narrow down the number of protein targets of auto-reactive antibodies identified in an earlier analysis of the sera from 13 patients with PANDAS and 9 patients with Autism Spectrum Disorder (ASD) to establish a “simpler” panel of proteins that will differentiate PANDAS patients from ASD patients. The sera of PANDAS patients, ASD patients and healthy (control) subjects will then be screened to determine the validity of the measure in diagnosing PANDAS.