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Innovative Research at OVC Could Advance Understanding of Alzheimer’s Disease

Brightfield micrographs of SH-SY5Y cellsBrightfield micrographs of SH-SY5Y cellsInnovative neuroscience research at the University of Guelph’s Ontario Veterinary College (OVC) could reveal more about the causes of Alzheimer’s Disease, as well as a potential treatment.

Drs. Bettina Kalisch and Tarek Saleh in OVC’s Department of Biomedical Sciences are studying regulatory mechanisms involved in gene expression. Cells can regulate their gene expression, and thereby the types of proteins they produce, by turning genes on or off. This regulation allows cells to respond to changing environments but can simultaneously lead to the production of malfunctioning proteins which have been linked to development of Alzheimer’s disease.

Andrila Collins, an MSc student in Biomedical Sciences at the Ontario Veterinary College, advised by OVC Profs. Bettina Kalisch and Tarek Saleh.Using cell culture systems, Kalisch and Saleh are exploring whether a novel antioxidant co-drug called VANL-100, could provide protection against the development of Alzheimer’s. Cell cultures can be an excellent experimental model for studying the effects of drugs or treatments on isolated, but living, cells outside of an organism.

Alzheimer’s disease is a progressive disorder in which proteins of the brain function abnormally, disrupt neurons, and ultimately lead to brain cell degeneration and even death. According to the Alzheimer’s Association, more than 747,000 Canadians are living with Alzheimer's or another form of dementia. Affected individuals suffer from memory impairment, a decline in thinking, behaviour and social skills, and eventually, the inability to carry out simple tasks. The number of individuals living with Alzheimer’s disease is expected to rise considerably over the next 20 to 30 years, and the demand for innovation in the prevention, diagnosis, and treatment of the disease through Alzheimer's research is rising with it.

Two main pathological hallmarks of the development of Alzheimer’s disease are, the presence of plaques and tangles in the brain caused by two malfunctioning proteins: amyloid-β protein fragments that cluster together abnormally to form damaging plaques, and tau proteins that change shape and cluster to form toxic tangles. Together, these malfunctioning proteins have toxic effects on healthy brain cells, slowly damaging and killing them.

Kalisch and Saleh aim to discover how the regulation of gene expression may be involved in production of amyloid-β protein, the major component of plaques. Specifically, their research focuses on oxidative stress —the imbalance between free radicals (oxygen-containing molecules with an uneven number of electrons that allow them to react more easily to other molecules) and antioxidants in your body— which has been implicated in the accumulation of amyloid-β.

“Currently, treatments available may help those living with Alzheimer’s to manage the disease by lessening symptoms, such as memory loss and confusion, for a limited time,” Kalisch says, “but there are no treatments available that target the underlying disease process responsible for the buildup of plaques and tangles that destroy neurons in Alzheimer’s disease.”. If there was a treatment with the ability to target and resolve the root cause of Alzheimer’s, patients may be able to recover, or at least live with a less severe form of the disease.

Improving the understanding of these cellular and molecular mechanisms could lead to novel disease-modifying treatment strategies. For these reasons, Kalisch and Saleh are in the early stages of research using isolated cells to explore the efficacy of VANL-100. This is a novel antioxidant co-drug which could provide protection against oxidative stress in cell culture systems.

If VANL-100 is found to protect nerve cells in this model, the team plans to translate their findings to assessment in a mouse model. VANL-100 could eventually serve as a treatment option for canine cognitive dysfunction, a behavioural syndrome characterized by the presence of amyloid-β plaques and similar symptoms to Alzheimer’s disease, which occurs naturally in older dogs.

Andrila Collins, an MSc student in Biomedical Sciences at the OVC, advised by Kalisch and Saleh, is also focusing on this research. Collins, pictured above, is a recipient of an OVC scholarship.