HEALTHY LIVING

2016 Nobel Prize Winner Yoshinori Ohsumi's Discoveries Could Change How We Treat Disease

His research could save your life.

04/10/2016 9:37 AM AEDT | Updated 05/10/2016 6:43 AM AEDT
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The 2016 Nobel Prize for physiology/medicine was awarded to Yoshinori Ohsumi of the Tokyo Institute of Technology for his research into autophagy.

Japanese scientist Yoshinori Ohsumi, 71, won the 2016 Nobel Prize on Monday for his research on autophagy ― a metabolic recycling process in which cells eat parts of themselves to survive and stay healthy.

His initial work, first started in 1992, focused on the genes behind the autophagy process in yeast cells. Autophagy, however, has implications for several human diseases, including cancer, neurodegenerative diseases, infectious diseases and diabetes. Now drugs that can target the process are being tested in early-stage clinical trials in human beings, which could fundamentally change everything from the way we treat dementia disorders to how we eradicate cancerous growths. 

Autophagy is a normal part of a cell’s lifespan. Individual cells can “eat” parts of themselves, especially old or damaged parts, and recycle the material to help keep themselves healthy. Think of it like recycling: By shedding damaged or dying parts inside the cell, the cell has a new resource from which to repair itself and keep itself running. 

Autophagy helps address normal damage and wear and tear to cells, but also plays a role in everything from fighting bacterial or viral infections to in-cell differentiation in embryo development. A dysfunctional autophagy process has also been linked to Type 2 diabetes and other genetic diseases, the Nobel Prize site notes. In particular, it may play an important role in two distinct disease types that are difficult to treat and mysterious in origin: cancer and neurodegenerative disease.

How autophagy affects brain diseases

When autophagy starts to slow down or stop functioning properly, the cell can no longer destroy its abnormal proteins, old cell structures and invasive germs. Currently, it’s unclear whether a dysfunctional autophagy process leads to disease, or whether disease has some other cause that leads to the disruption of autophagy. The neurodegenerative disorder Parkinson’s disease is a good example: It’s characterized by the presence of Lewy bodies ― abnormal packets of protein, spread throughout the brain.

Scientists have linked dysfunctional autophagy processes to the accumulation of Lewy bodies. Jay Debnath, a professor of pathology at the University of California, San Francisco, who is using Ohsumi’s discoveries to develop breast cancer treatments, explained that this could be because brain cells have stopped “eating” abnormal proteins.

In the same way, amyloid plaques, another kind of damaging protein, may also accumulate if the autophagy process breaks down. Researchers suspect Amyloid plaques cause Alzheimer’s disease

Turning the autophagy process back on in people with neurodegenerative diseases may slow or halt the accumulation of these harmful protein growths in the brain.

Debnath says that targeting autophagy to improve its functioning might be one way to treat neurodegenerative diseases like Parkinson’s disease or Alzheimer’s disease. 

How autophagy actually helps cancer cells grow

A malfunctioning autophagy process may be linked to disease, but researchers are also studying whether the opposite could be true ― that when autophagy is too efficient, it could help cancer cells grow and spread. Accelerated autophagy allows tumor cells to grow and regenerate at a faster rate than normal. Finding therapies that can slow down or halt this process may be key in helping traditional cancer treatments like chemotherapy kill cancerous cells more effectively.

“In cancer cells, one of the thoughts is that you want to turn the process off in order to potentially make those cancer cells more adaptable to die during chemotherapy and other types of therapy,” Debnath explained.

He has been studying the autophagy process in cancer cells since 2005. He’s trying to see whether he can slow or arrest the autophagy process in cancer cells to make cancer therapies more effective, and he’s also studying the potentially harmful effects of completely stopping the autophagy in healthy cells. 

Specifically, Debnath is investigating if disrupting the autophagy process can halt breast cancer progression.

Several early-stage clinical trials are looking into whether therapies to slow or stop the autophagy process can help make chemotherapy or radiation better at targeting and killing cancerous cells. By putting a stop to cancerous cells’ efforts to renew and regenerate themselves, the thinking goes, traditional cancer therapies have a better chance at killing them.

On the opposite end of the spectrum, therapies to help re-start the autophagy process may help cells clear the toxic proteins that are inhibiting their function. For instance, in a small phase 1 trial, people with Parkinson’s disease and Lewy body dementia who received a small, daily dose of an FDA-approved leukemia drug that happens to promote autophagy experienced improvements in motor skills and cognition over six months.  

Ohsumi’s discoveries in autophagy shed light on a cellular process that scientists had known about for decades, but did not understand in terms of its importance to physiological health and the potential for treating certain diseases. After receiving news of his Nobel Prize win in Tokyo Monday morning, Ohsumi invited younger scientists to join him on his quest to continue learning more about autophagy, reports the AP. 

“There is no finish line for science. When I find an answer to one question, another question comes up. I have never thought I have solved all the questions,” Ohsumi said. “So I have to keep asking questions to yeast.”

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