PANDAS Families Are Acting as Citizen Scientists to Find Genetic Link With Strep
PANDAS Network has followed over 200 families for over a decade. Now genetics are being analyzed with Dr. Dritan Agalliu, neuroscientist at the Columbia University Medical Center, on a groundbreaking new PANDAS study.
At PANDAS Network, one of our main goals is to help spread education and awareness about PANDAS/PANS. That’s why we’re excited to share some recent and upcoming research developments thanks to a long partnership with Dr. Dritan Agalliu’s Neuroscience Lab at the Columbia University Medical Center. Dr. Agalliu is currently the only researcher focusing exclusively on the connection between specifically strep bacteria and the neuroinflammation and autoimmune response responsible for PANDAS symptoms.
Below, we discuss Diana Pohlman and PANDAS Network’s partnership with Dr. Agalliu, what this ongoing research study hopes to find, and how a growing sense of community and solidarity has helped the participants through recent years.
Partnering With Dr. Dritan Agalliu, Neuroscientist, Columbia University on Genetic Research
Diana was first put in contact with Dr. Agalliu when her own children began experiencing PANDAS symptoms about a decade and a half ago. At that time, the nationwide community of families who knew they were dealing with PANDAS was even smaller, and Dr. Agalliu was one of the only researchers investigating the role of strep infections as a precursor to the disease’s neuroinflammation and psychiatric symptoms. During this time, Diana—who is not a researcher herself—began to advocate strongly for the importance of research studies and doctor education in helping families fight PANDAS. Working with Dr. Agalliu became a natural extension of this focus on research advocacy.
Over the course of the last 15 years, Diana, in partnership with other doctors, and Dr. Agalliu, have followed roughly 200 families of children with PANDAS, with the goal of clarifying whether there is a genetic predisposition to the adverse strep reaction that they think is responsible for causing the disease. The question was: Will PANDAS children relapse into adulthood?
“It’s almost like a genetic ‘allergy’ to strep,” says Diana. The study will use biosamples from the participants to look for specific gene mutations that may indicate a sensitivity to strep. Finding a common genetic variant across many members of the cohort could help researchers identify why certain children develop PANDAS from this otherwise common infection.
All of the children in the study cohort initially got sick around ages 7-10 and are now 18-25 years old. Of the 200 families followed, roughly 40% have had relapses in their late teens or early 20s, always due to an additional infection like strep, pneumonia, mononucleosis, or COVID-19. With quick antibiotic or IVIG treatment, those who have relapsed report they feel they have made full recoveries. Diana wants families to know that PANDAS is manageable with the right treatments and education about the condition from the early stages. This is one reason that finding clear genetic risk factors could be such a significant step for all the families struggling with PANDAS—not just now, but also in the future.
In addition to this ongoing genetic research study, Dr. Agalliu will soon publish research findings on potential biomarkers for PANDAS. This additional research aims to identify a biomarker that can be used to more effectively diagnose PANDAS in the early stages by showing how repeated strep infections change T-cell behavior—specifically how T helper cell 17 (Th17) signals cytokines that trigger neuroinflammation and damage to the blood-brain barrier.
Why focus specifically on strep? (Connections to Rheumatic Fever and Other Autoimmune Diseases)
This research comes at a time when families have gotten used to hearing doctors and researchers downplay or outright dismiss the role of strep infections in PANDAS. “For years we’ve heard that ‘strep cannot do this to a person’s brain,’” Diana says, despite evidence that there is a clear causal connection between strep and PANDAS. “We know that strep can cause inflammation and an autoimmune response, but we’ve never understood why it becomes Sydenham chorea or PANDAS.”
Researchers like Drs. Madeleine Cunningham and Chandra Menendez, University of Oklahoma strep experts, believe that families like those in Dr. Agalliu’s research group may be descended from ancestors who were genetically predisposed to be vulnerable to rheumatic fever. Entire families used to be devastated by rheumatic fever outbreaks, but now that instances of the disease in some parts of the world have dropped, strep bacteria is evolving in new ways to target people with this genetic “allergy.” (Globally there are still many areas where rheumatic fever poses a more frequent, consistent threat, with more than 300,000 people dying of rheumatic heart disease every year.)
The majority of the 200 families that have been followed have at least one parent with an autoimmune disease, such as inflammation-causing conditions like, for example, rheumatoid arthritis, celiac disease or ankylosing spondylitis. Diana herself has a mild variant of multiple sclerosis, an autoimmune disease that causes the body’s immune system to attack the myelin lining that protects nerve fibers in the brain and spinal cord.
Identifying a genetic predisposition to strep would go a long way toward explaining the “allergic” response some children suffer to this otherwise very common bacteria. This would in turn help families identify whether children are at higher risk for developing PANDAS following a strep infection and could act as an early indicator for doctors of the need for antibiotics or more intensive treatments like IVIG.
Identifying Genetic Links Between Strep Infections and PANDAS
Many doctors and researchers group Sydenham chorea and PANDAS in with all PANS conditions, which ignores the specific role of strep infections in the formation of each disease. By establishing a genetic basis for certain children’s predisposition to strep, Diana says the group “hopes that in a decade we can put to rest the debate about PANDAS and Sydenham chorea” as distinct neuroinflammatory diseases with their own unique pathologies.
Dr. Agalliu’s disease model has focused in animal model on strep onset in PANDAS cases in an effort to understand why some children develop a neuroinflammatory response to strep bacteria while many others do not, even after multiple strep infections. (As research has continued PANS cases children cases have very similar processes.) It is substantiated clearly that PANDAS stems from basal ganglia encephalitis (BGE)—a swelling of the brain that has been tied to group A strep infections. In a typical immune response, the body produces antibodies that target the harmful strep bacteria until the infection subsides. For the many children who get strep throat each year and recover, the body’s immune response to strep stops here. However, in children with PANDAS, the body’s immune response fails to respond this way—Dr. Agalliu’s research hopes to clarify specifically why this is.
Diana and Dr. Agalliu are working to show that some children’s immune systems exhibit a kind of “allergic reaction” to strep. This hyper-sensitivity to the bacteria causes their immune response to instead target the brain and induce blood-brain barrier damage, antibody entry into the brain, neuroinflammation and neural circuit dysfunction. This results in the movement-based symptoms of Sydenham chorea and the acute psychiatric response seen in PANDAS.
Research Cohort Turned Long-Term Support Community
For the families and children dealing with the long process of recovery from PANDAS, this group has often been more than simply participants in a research study. Over the course of the last 15 years, the families in the cohort have grown from disparate individuals affected by the same under-researched disease into a group of citizen scientists allied around the fight for awareness. They have stuck together through years of uncertainty, PANDAS relapses, the heightened fear of infection during the COVID pandemic, and more.
These families have developed into an essential support network for each other and have shown incredible patience especially throughout the COVID-19 pandemic, which disrupted the group’s attempts to collect research samples. (All samples were sent out and returned via mail, which at times ground to a halt during the worst stages of the pandemic.) Diana and Dr. Agalliu are now working on re-sending sample collection kits to all the families in the relapse young adult cohort. These most recent requests for samples will also be accompanied by a survey to help gather data about participants’ symptoms and establish a clear timeline of disease progression.
Diana gets calls all the time from families who are dealing with one or multiple children suffering from PANDAS, and who can’t get answers from doctors about the condition or how to treat it. Finding a concrete genetic link between strep and PANDAS would be a huge step forward in understanding this disease. Families know there is immense value in simply making PANDAS research more widely known and accessible to family doctors who may otherwise be hesitant to embrace treatment options.
Currently, Diana and Dr. Agalliu are trying to increase the cohort size for the study to 300 participants. It’s too early to know for sure what the results of the study will yield. “We may fail. We may not find a specific genetic marker,” says Diana. “But at the very least, this research can prove inflammatory processes and establish biomarkers for PANDAS and Sydenham chorea, and can provide some comfort to parents and children suffering from acute psychiatric symptoms.”
Learn more about the latest PANDAS research, including diagnosis and treatment options. Remember, you do not have to face the fight against PANDAS alone. PANDAS Network can connect you to support groups in your area as well as clinician resources that can help you explain your child’s condition to their doctor.