An innovative nasal spray treatment has shown promising results in eliminating harmful accumulation of tau protein in the brain and improving cognitive functions in aged mouse models with neurodegenerative diseases. This significant advance in the fight against this type of pathology, which includes Alzheimer’s and dementia, has been achieved by a group of researchers from the University of Texas Medical Branch (UTMB), in the United States.
“This nasal spray approach opens new avenues for noninvasive delivery of therapeutic tau antibodies directly to the brain, and promises to be useful for many neurodegenerative diseases,” said Dr. Rakez Kayed, senior author and professor in the Department of Neurology at UTMB. The study results were published in Science Translational Medicine.
Tau is a protein present in the human brain associated with microtubules, which helps stabilize these components that are part of the skeleton that gives shape and organization to neuronal cells. In healthy brains, tau proteins maintain order, but in neurodegenerative diseases they can twist abnormally and form tangles that interfere with neuronal function and cause cognitive impairment. Current immunotherapies for tau have had problems with their efficacy due to their limited ability to penetrate the intracellular compartments where these proteins accumulate.
Nasal immunotherapy against tau to treat neurodegenerative pathology
Kayed and his team developed a specific type of antibody called TTCM2, which selectively recognizes and targets the toxic buildup of tau. This antibody was packaged into particles to enhance its delivery to the brain via the nasal route. This method bypasses the blood-brain barrier, a significant obstacle in the treatment of neurodegenerative diseases, 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 such as Alzheimer’s and other tauopathies,” Kayed added. “This approach not only improves the delivery of therapeutic antibodies, but also increases their efficacy in clearing tau aggregates and improving cognitive functions.”
“This breakthrough could have a significant impact on treatment strategies for Alzheimer’s and related tauopathies”
A key aspect of this approach is the involvement of TRIM21, an intracellular antibody receptor and E3 ligase known to mediate the clearance of antibody-bound pathogens such as viruses. In the study, TRIM21 facilitated the clearance of antibody-bound intracellular tau aggregates, thereby enhancing the therapeutic effect and cognitive improvements in the mouse model.
“This breakthrough could have a significant impact on treatment strategies for Alzheimer’s and related tauopathies, offering new hope to millions of patients suffering from these disabling conditions,” said Sagar Gaikwad, first author of the study and a postdoctoral fellow at UTMB.
This study highlights the potential impact on future treatments for neurodegenerative diseases. UTMB researchers plan to advance this research by conducting further preclinical trials and exploring the potential of TTCM2-ms in human clinical trials, with the goal of translating these promising results into a viable treatment option for patients suffering from Alzheimer’s and other tau-related disorders.
