In March, Moussa Youdim, BSc’62, MSc’64, PhD’66, received the prestigious Israel Prize for the Life Sciences for his outstanding scientific accomplishments in the field of neuropharmacology. Research by Youdim, whose foray into biochemistry began at McGill, has led to important insights into the biological underpinnings of neurodegenerative diseases—and novel therapeutics to treat them.
Winning this award was a “wonderful feeling,” says Youdim, a professor emeritus at the Technion – Israel Institute of Technology and president of Youdim Pharmaceuticals. “It’s the biggest honour Israel can give a citizen.”
Youdim was born in Tehran, Iran. When he turned 12, his parents sent his brother and him to England, where he went to boarding school from 1952 to 1959. An acceptance to McGill led him to Montreal to start the next chapter of his education.
At McGill, Youdim became captivated by the biochemistry of the brain after listening to a lecture on the development of the first-ever antidepressant. Youdim’s father had struggled with a deep depression in the 1950s, when there were no drugs to treat the illness. Instead, his father had been taken to the hospital for electroshock therapy. Upon hearing that there might be a pharmaceutical treatment for depression, Youdim’s interest was instantly piqued: “I said to myself, this is going to be the great new frontier of science.”
Youdim decided to pursue his doctoral education in biochemistry and psychiatry. As a graduate student, Youdim was stationed at the Allan Memorial Institute, where he worked with Theodore Sourkes—a biochemist and neuropharmacologist who went on to make foundational contributions that led to the development of levodopa (L-DOPA), a drug that replenishes dopamine, a neurotransmitter that gets depleted in patients with Parkinson's disease.
As a graduate student in the 1960s, Youdim decided to focus on studying monoamine oxidase (MAO), enzymes that aid the degradation of important molecules released by brain cells, such as dopamine and serotonin. At the time, MAO inhibitors were being used as antidepressants. These investigations of MAOs marked the “beginning of my venture into neurochemistry,” Youdim says.
During this period, Youdim helped characterize two separate forms of monoamine oxidases—enzymes that aid in the degradation of important molecules released by brain cells, such as dopamine and serotonin—which were later dubbed MAO-A and MAO-B. A key difference that marks these two classes of MAO are in the molecules they metabolize: MAO-A, for example, prefers serotonin and norepinephrine.
Treating neurodegenerative diseases
After receiving his PhD from McGill in 1966, Youdim returned to England to carry out his postdoctoral studies with Merton Sandler, a professor of chemical pathology at the Queen Charlotte Maternity Hospital in London. There, Youdim continued his work on MAOs. In one of his studies, he discovered that a deficit in MAO activity explained why cheese was a common trigger for migraines.
While at an academic meeting in Italy in 1972, Youdim met Joseph Knoll, a Hungarian scientist and Holocaust survivor who had pinpointed a MAO-B inhibitor dubbed selegiline (R-deprenyl). The drug had failed as an antidepressant, Youdim says, becoming instead a tool for researchers. But at the back of his mind, Youdim suspected that the drug could be much more.
Soon after, when Youdim was a faculty member at Oxford University, he worked with neuroscientist Peter Riederer and neurologist Walther Birkmayer, to uncover selegiline’s ability to treat Parkinson’s disease. As a MAO-B inhibitor, selegiline works by blocking the breakdown of dopamine and increasing its availability in the brain.
In 1975, Youdim was asked to establish and lead a new pharmacology department in the Technion – Israel Institute of Technology’s Faculty of Medicine. Once he accepted the position, Youdim left Oxford and headed to Haifa, Israel, to take up this post. At the Technion, Youdim worked with John Finberg, another professor at the Technion, to demonstrate the potential of another MAO-B inhibitor, rasagaline, as a treatment for Parkinson’s disease. “This drug, pharmacologically, acted like the drug from Hungary,” Youdim says. “And it was even more potent.”
Despite these promising findings, Youdim says it took many years to convince a company to buy the drug. But years of persistence paid off—the pharmaceutical company Teva licensed rasagaline (Azilect) in the late 1980s. Today, Parkinson’s patients receive the drug either alone or in combination with L-DOPA in Europe in 2005 and the United States in 2006. The drug is currently availability in 45 countries, including Canada and the United States.
“The development of rasagaline, which is one of the most prescribed drugs for Parkinson’s, is helping millions of people,” says Prof. Claudio Cuello, the Charles E. Frosst Merck Chair in the McGill Department of Pharmacology and Therapeutics and a long-time friend and colleague of Youdim.
During his decades-long career, Youdim has published hundreds of articles, received many awards and honours, and held positions at numerous prestigious institutions around the globe. Youdim’s research shed light on the molecular underpinnings of neurodegenerative diseases and led to the development of other therapeutics, such as the anti-Alzheimer drug ladostigil, which works in part by acting on MAOs in the brain.
Youdim has also been a generous champion of McGill University. Notably, he rallied others to join him in enabling the creation of the Theodore L. Sourkes Lecture Series, which honours Youdim’s late mentor through talks given by leading researchers in neuropharmacology and Parkinson’s disease from around the world.
Youdim is “very deserving” of the Prize for the Life Sciences, Cuello says. “Beyond being a successful scientist, Moussa is also a very kind and passionate person.”