From the Gene to the Clinic
\nKhaoula Ben Haj Frej
\nDr. Douglas Macdonald ’89<\/p>\n
Who wouldn\u2019t want to be able to find the cure for Huntington\u2019s Disease? Dr. Douglas Macdonald, a Trinity alum, is a research who claims to be on the road towards realizing this goal. In his lecture \u201cFrom the Gene to the Clinic,\u201d he began by showing images of a brain with and without Huntington\u2019s disease, showing a loss of brain tissue with the progression of the disease. While everyone loses brain matter with the years, brain neurons are lost at a much faster rate in patients. He related his studies and general neuroscience to the subject of Michelangelo\u2019s Sistine Chapel, where a figure encased in what seems to be a brain bestows knowledge on a man directly below him.
\nAccording to the speaker, Huntington\u2019s disease is an inheritable neurodegenerative and peripheral disease rampant in families, as only a single chromosome with the disease is needed to have it. Neurodegenerative diseases involve the loss of \u201cspecific neural populations\u201d(Sajuan and Bates, 2015); according to Dr. Macdonald, this loss is characterized by increased ventricular space in people with Huntington\u2019s Disease. Furthermore, regions in the brain affected by neuon degeneration are parts of the corpus striatum, cortical pyramd, motor, frontal, and occipital cortices, and the hypothalamus (Sanjuan and Bates, 2015). The disease is also late onset, impacting those in their early 40\u2019s, so those who have it have often already had children who have a 50% chance of also having the disease, discovered serendipitous. In fact, it is rampant in Lake Maracaibo, in Venezuela, where thousands of people have the disease. Detecting the disease, often by detecting the protein to which it is attributed, can be incredibly difficult to diagnose in vivo (Chase, 2015). Dr. Macdonald suggests a \u201cdisease modification\u201d approach to fight the disease (Sanjuan and Bates, 2015).
\nSome challenges of this research, includes questions like \u201cWhat to target\u201d so that knockdown is sufficient, \u201cwhere to treat\u201d in the brain, \u201cHow much to suppress\u201d so that minimum suppression can occur, and finally \u201cwhen to treat\u201d for optimal results. The answer to that last question is probably, \u201cas early as possible.\u201d Today, there are no curing therapies for Huntington\u2019s disease. Currently, many therapies are symptomatic intervention, attempting to reduce or cure symptoms. Others are disease modifying, where the disease is treated very early on, delaying the onset of symptoms.
\nDr. Macdonald\u2019s research is currently attempting to combine pharmacology and therapy that cure the disease itself. The cause of the disease is known; all that is left is preventing its onset. From the gene to the protein, you can intervene at different steps, like transcription, translation, and clearance. Current, pharmaceutical and biotechnology companies work with the clinic to lower or suppress Huntington\u2019s gene expression in brains with the disease. So far, HTT ASO\u2019s have shown reversal and sustained beneficial effects in BACHD mice, or those with the disease. When it comes to drugs, the location of the drug\u2019s introduction is incredibly important. For example, in the NHP striatum in the brain, AAV2-HD5 can lower Huntington protein, reducing expression in that area. Thus Huntington\u2019s was knocked down, without also killing the neurons. Right now, PET tracers are also being considered as biomarkers for the disease, thanks to clinical data with mice.<\/p>\n","protected":false},"excerpt":{"rendered":"
From the Gene to the Clinic Khaoula Ben Haj Frej Dr. Douglas Macdonald ’89 Who wouldn\u2019t want to be able to find the cure for Huntington\u2019s Disease? Dr. Douglas Macdonald, a Trinity alum, is a research who claims to be … Continue reading