Randall Urban, MD
Vice President for Research &
Chief Research Officer

Dr. Randall Urban

Dr. Randall Urban leads a diverse research community in the bold mission to improve medical practice through progressive translational research endeavors. He has 145 peer-review publications, is the Principal Investigator of UTMB's Clinical and Translational Science Award, and has 3 major research interests funded by the NIH and private foundations. In addition to Vice President for Research and Chief Research Officer, Dr. Urban is Vice Dean for Clinical Research in the John Sealy School of Medicine, Professor of Internal Medicine, Director of the Institute for Translational Sciences, and Fellow, John P. McGovern Distinguished Chair in Oslerian Medicine.

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The Strategic Research Plan, which is used by leadership to  develop a path forward through goals, objectives and tactics, has broad input. It includes six integrated health communities that bring together researchers, educators, clinicians and community members to use prevention and treatment to transform illness to health. Read more.

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New Breakthrough in Alzheimer’s Research: UTMB Researchers Develop Nasal Spray Treatment for Alzheimer’s Disease

Researchers at the University of Texas Medical Branch recently discovered a significant advancement in the fight against neurodegenerative diseases such as Alzheimer’s disease and dementia. The study, published today in Science Translational Medicine, introduces an innovative nasal spray treatment that has shown promising results in clearing harmful tau protein build-up and improving cognitive functions in aged mice models with neurodegenerative diseases.  

“This nasal spray approach opens new avenues for non-invasive delivery of tau therapeutic antibodies directly to the brain, and it holds promise for many neurodegenerative diseases.” said Dr. Rakez Kayed, lead author and professor at the Department of Neurology at UTMB.  

Tau is a microtubule-associated protein found in human brains that helps stabilize microtubules, part of the framework that gives the cell its shape and helps it stay organized, in neurons. In healthy brains, tau proteins help keep things in order. But in neurodegenerative diseases, they can become abnormally twisted and form tangles that disrupt neuronal function and lead to cognitive decline. Current tau immunotherapies have struggled with efficacy due to their limited ability to penetrate intracellular compartments where these tau buildups reside. 

Kayed and his team developed a specific type of antibody, TTCM2, which selectively recognizes and targets toxic tau buildup. The antibody was packaged in particles to enhance its delivery to the brain via the nasal route. This method bypasses the blood-brain barrier, a significant hurdle in neurodegenerative disease treatment, ensuring rapid and effective delivery of the therapy. 

 “Our research highlights the potential of nasal tau immunotherapy to effectively target intracellular tau aggregates– a primary driver of neurodegeneration and cognitive decline in diseases like Alzheimer’s and other tauopathies,” added Kayed. “This method not only improves the delivery of therapeutic antibodies but also enhances their efficacy in clearing tau aggregates and improving cognitive functions”.  

An essential aspect of this approach is that it involves TRIM21, an intracellular receptor for antibodies and E3 ligase, known for mediating the clearance of antibody bound pathogens like viruses. In the study, TRIM21 facilitated the clearance of antibody bound intracellular tau aggregates, thereby enhancing the therapeutic effect and cognitive improvements in the mice model. 

 “This advancement could significantly impact the treatment strategies for Alzheimer’s and related tauopathies, offering new hope for millions of patients suffering from these debilitating conditions,” said Sagar Gaikwad, first author of the study and postdoctoral fellow at UTMB. 

This study highlights the potential impact on future treatments for neurodegenerative diseases. Researchers at UTMB plan to advance this research by conducting further preclinical trials and exploring the potential of TTCM2-ms in human clinical trials. The goal is to translate these promising results into a viable treatment option for patients suffering from Alzheimer’s disease and other tau-related disorders. 

The study was funded by grants from the NIH, Alzheimer’s Association and UTMB Claude D. Pepper OAIC Pilot grant. Authors and investigators also include Nicha Puangmalai, Minal Sonawane and Mauro Montalbano from UTMB.