Understanding the disease

Alzheimer’s disease (AD) is one of the most deleterious disorders in the aged population. To date, we do not have a drug to treat the disease. Our research focuses on several pathways to understand the disease process and develop potential targets for therapeutic intervention. We are looking at the impact of proteins such as neprilysin and the receptor for advanced glycation endproducts (RAGE) that are important in the disease process. We are looking at the role of inflammation (neuro and systemic) by studying the impact of serum amyloid P component (SAP) and serum amyloid A (SAA) proteins in AD. We also study the impact of the environment and transgenerational epigenetic effects in AD. In addition, we are developing unique vaccines for the treatment of the disease. Using transgenic and gene knockout mice as well as viruses, we can dissect how the disease develops and progresses.

Inflammation

Stroke is the second leading cause of death worldwide and is the primary cause of disability in the USA. The pathophysiology of cerebral ischemic injury is complex, and numerous studies have demonstrated that oxidative stress and inflammation are key in the underlying mechanisms. We have developed unique animal models of health disparities (stroke risk factors such as diabetes, obesity, cardiovascular disease, hypertension, etc.) to better understand the mechanisms associated with stroke. We are studying the impact of SAAs in stroke and the potential for therapeutic interventions. We are also using MRI studies to develop connectomes in the brain following a stroke to help us understand how these changes occur.

Neuroinflammation

Traumatic brain injury (TBI) is the leading cause of death and disability in adults under the age of 45, affecting ∼20% of veterans from recent wars. Once thought to be a monophasic injury, TBI is now known to trigger an indolent neurodegenerative process that substantially increases the risk of Alzheimer’s and other forms of dementia for older veterans. All disability resulting from TBI stems from its disruption of functional neural networks. The mechanisms by which TBI interrupts these networks and sets up further neurodegenerative network breakdown are inadequately defined, though injury loci beyond those observed in white matter are increasingly recognized. Our studies will help define the role of inflammation in TBI and the potential for a targeted approach using nanoparticles and other approaches.

Neuroengineering

The need for neural tissue engineering arises from the difficulty of the nerve cells and neural tissues to regenerate on their own after neural damage has occurred. The PNS has some, but limited, regeneration of neural cells. Adult stem cell neurogenesis in the CNS has been found to occur in the hippocampus, the subventricular zone (SVZ), and spinal cord. CNS injuries can be caused by stroke, neurodegenerative disorders, trauma, or encephalopathy. A few methods currently being investigated to treat CNS injuries are: implanting stem cells directly into the injury site, delivering morphogens to the injury site, or printing neural tissue in vitro with neural stem or progenitor cells in a 3D scaffold.

Industrial Hemp

In light of the therapeutic implications of cannabis and medical marijuana, the Botanical Medicine Research and Education Consortium (BMREC) in the College of Pharmacy at the University of South Florida aims to:

A) Establish a Clinical Research Program (CRP) to advance our understanding of the impact of cannabis (cannabinoid-like molecules), hemp derived and other botanical materials in the clinical setting, that will focus on the testing of compounds currently in the research space as well as those developed by the BMREC. Dr. Sanchez-Ramos will oversee the clinical trials that will be researcher initiated, company sponsored and NIH funded;

B) Develop a Basic Science Research Program (BSRP) for drug discovery technology to determine the components in cannabis (THC, CBD, CBG, CBN, etc.) and other botanic species for their therapeutic potential in various diseases both in vitro and in vivo. For these studies, Dr. Kindy will oversee the basic sciences projects that will focus in development of cannabis- and botanical-derived compounds in various animal models (mice, rats, dogs, pigs, etc) to determine the efficacy in diseases (Alzheimer's, Parkinson's, traumatic brain injury, cardiovascular disease, inflammatory diseases, etc.). In addition, the Consortium will study combinations of botanical agents, dosing regimens, pharmacokinetics, ADME, toxicology, formulations and drug delivery. Protocols will be developed to determine the therapeutic potential of these various formulations of botanical medications.

C) Establish an educational program related to other potential Botanical Medicines, in addition to medical cannabis, which will foster innovative approaches to teaching and learning, deliver educational programs, and enhance technology development. As indicated, the consortium will work with various universities, corporate entities, and foundations to provide the clinical, basic and outreach opportunities for dissemination of the information generated by the center.