The University of Rochester Intellectual and Developmental Disabilities Research Center is transforming the landscape of exploration.
Batten disease is a devastating rare genetic disorder. While the genetic flaw that causes this disease is well known, scientists do not fully understand the connection between this mutation and the disease’s symptoms like behavioral changes, cognitive impairment, seizures, and vision loss. John Foxe, PhD, co-director of the University of Rochester Intellectual and Developmental Disabilities Research Center (UR-IDDRC), recently described a potential neuro marker for the disease that could represent a way to better understand this complex disease and, ultimately, help researchers measure outcomes in clinical trials.
“We [researchers] know it is a genetic single gene mutation that causes Batten disease and as a scientist that really gives us something to focus on,” said Foxe, who is also director of the Del Monte Institute for Neuroscience at the University of Rochester. “But clinically, what we do not fully understand is how the mutation changes connections in the brain. Our work has been aimed at developing a much better understanding of these changes and developing ways to measure these accurately. If we can figure out how to treat Batten disease, there's a very good chance we will gain insight into how to treat other rare diseases.”
The University is a recognized leader in Batten disease research and care and has been at the forefront of efforts to understand and treat this condition. The University of Rochester Batten Center (URBC) is designated as a Center of Excellence by the Batten Disease Support and Research Association (BDSRA), highlighting its commitment and expertise in advancing both research and treatment for this disease. In 2020, when the National Institute of Child Health and Human Development (NICHD) designated the University as an IDDRC, the disease became the Center’s principal project, and researchers identifying biomarkers to evaluate the effectiveness of experimental treatments became a renewed focus for faculty at the Medical Center. Foxe’s latest research, published in the Journal of Neurodevelopmental Disorders, is one example of how the IDDRC designation is transforming the IDD research landscape at the Medical Center.
Upgrading resources, uniting teams
The structure of the UR-IDDRC has propelled the relationship between discoveries at the bench and clinicians. The Center has four scientific cores—Human Clinical Phenotyping and Recruitment, Translational Neuroimaging and Neurophysiology, Animal Behavior and Neurophysiology, and Cell and Molecular Imaging. These cores enhance access to resources, equipment, data, and expertise, advancing research at the University in new ways.
The Cell and Molecular Imaging (CMI) core provides access to state-of-the-art equipment and expert support for those looking to utilize it. Currently, research utilizing CMI is developing a human model of iron deficiency using brain organoids—a mass of cells, in this case, that represents a brain that is so small a microscope is needed to study it. This research led by Margot Mayer-Proschel, PhD, professor of Biomedical Genetics and Neuroscience, and supported by a UR-IDDRC pilot grant, builds on her lab’s previous work that identified a new embryonic neuronal progenitor cell target for gestational iron deficiency. This research could inform the connection between gestational iron deficiency and IDDs, change health care recommendations, and provide potential targets for future therapies. It is well understood that low levels increase the risk of cognitive impairments like autism, attention deficit syndrome, and learning disabilities.
Our labs are working together on research related to per- and polyfluoroalkyl or PFAS, also known as ‘forever chemicals’. In fall 2023, a new 9.4T MRI arrived at the Center for Advanced Brain Imaging and Neurophysiology (CABIN) at the Medical Center. This state-of-the-art imaging system is available to investigators through the Translational Neuroimaging and Neurophysiology core. It joins the ranks of Mobile Brain/Body Imaging or MoBI and high-density electroencephalogram or EEG.
“It [UR-IDDRC] has provided absolutely critical infrastructure through the scientific cores and then through all its activities,” Foxe said. “Our successful symposiums have brought researchers from around the world to Rochester. The IDDRC has also brought scholarship opportunities and students. It has coalesced the IDD community at the University like never before.”
The University is one of eight institutions with the trifecta of federal awards related to IDDs, giving a nod to its research, training, care, and community partnerships. Along with the IDDRC, it has long been a University Center of Excellence in Developmental Disabilities Education, Research, and Service (UCEDD) and Leadership Education in Neurodevelopmental and Related Disabilities (LEND). The UCEDD focuses on training and community service, while the LEND focuses on education. The three entities continue to innovate new collaboration opportunities. Most recently, a retreat brought more than two dozen people from across the three entities together to brainstorm, collaborate, and strengthen relationships.
Tackling a challenge protects the vulnerable
Within a year of receiving the IDDRC designation, the resources and expertise at the University were tested. As the COVID pandemic raged, the NIH looked to IDDRCs to help its efforts in understanding the impact of the virus on the IDD community. UR-IDDRC and Mary Cariola Center, an education and life skills center for people with severe IDDs and complex medical needs, teamed up and took on the $4 million project, funded by the NIH Rapid Acceleration of Diagnostics- Underserved Populations (RADx-UP) program.
“This was an unbelievably successful project,” Foxe said. “We were able to respond in a matter of weeks to a critical need in our community because we already had infrastructures set up and community partners in place.”
The access to testing allowed Mary Cariola to comply with state mandates and provide real-time results to researchers that kept COVID out of classrooms on several occasions by identifying asymptomatic cases. The data collected by this study will inform how airborne illnesses are responded to and hopefully mitigated in this type of setting.
The future: From bench to bedside
The UR-IDDRC continues to support research progress through new equipment and pilot funding, while attracting new talent to the University and the field. “The IDDRC designation is elevating the awareness of what we are doing in this space,” said Majewska. “And it has certainly helped with recruiting students. People get very excited about it. The IDDRC has become the nucleus of the work that has been underway at the University for decades. It has strengthened it, allowed us to purchase new state-of-the-art equipment, fostered new collaborations, and given resources to investigators here to take their research in new and exciting directions.”
Thirty peer-reviewed research papers have been supported by the Center since 2020, and faculty have established new labs. Emily Knight, MD, PhD, assistant professor of Pediatrics and Neuroscience and principal investigator of the Spectrum Brain Lab, is a physician-scientist who was a fellow in the LEND program before becoming a faculty member in 2022. She was recently awarded a UR-IDDRC pilot grant to investigate the deficits in mechanisms in the auditory processing system that impact how children with autism process language in a noisy environment.
The IDDRC designation has leveraged the already robust IDD research at the University. It has established a clear pathway from bench to bedside by uniting the IDD research underway at the University with the already well established UCEDD and LEND programs. “I think it’s a very exciting thing to be partnering with people who look at the same thing from a very different perspective,” Foxe said. “We are learning from each other and sharing resources. I’m energized by what we’ve been able to accomplish so far and am looking forward to the future.”
This article was originally published in NeURoscience Volume 20.