Technion Research Helps Those with Neurodegenerative Diseases

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Green Tea May Hold Answers 

Fortune tellers have claimed they can see people's futures in tea leaves. But when Technion researchers look at tea leaves they see a much brighter future for victims of Parkinson's, Alzheimer's and other neurodegenerative diseases.

Prof. Mousa Youdim and Dr. Silvia Mandel (vice director of the Parkinson Foundation Centers) have found that EGCG, a powerful antioxidant that protects the brain neurons from dying, is one of the main components of green tea. They are continuing to study the active ingredients in green tea to determine if they can keep Parkinson's at bay and are hoping to determine its clinical potential in such patients with their colleagues in the U.S.

In the video below, Dr. Mandel elaborates on these antioxidant properties of green tea.

The Technion is a leader in combatting the progression of the neurodegenerative diseases Parkinson's, Alzheimer's and Multiple Schlerosis (MS) thanks to groundbreaking research conducted there.

FDA Gives Green Light to Parkinson's Drug

Breakthrough Drug Developed By Two Technion Professors

Moussa Youdim and John Finberg

Technion Profs. Moussa Youdim and John Finberg

Azilect, a breakthrough drug for Parkinson’s disease developed by Technion scientists, has been approved by the FDA.  It is now being marketed in the United States by Teva Pharmaceutical Industries, Ltd., bringing hope to the 1.5 million Americans who already have this debilitating and incurable brain disorder as well as to the 60,000 new patients diagnosed each year.

Parkinson’s disease occurs when, for unknown reasons, nerve cells in the brain that produce a chemical called dopamine die. One of dopamine’s functions is to ensure that the body’s muscles are coordinated and move smoothly.  Without it Parkinson’s sufferers experience tremors, rigidity and slowness of movement.

“The problem with Parkinson’s disease is that by the time a patient notices that something is wrong and goes to the doctor, he has already lost 50-70 percent of his dopamine-producing nerve cells in the brain region called substantia nigra,” explains Professor John Finberg of the Department of Pharmacology at the Technion Faculty of Medicine. Professor Finberg along with his colleague, Professor Moussa Youdim, are responsible for the development of Azilect.  These lost nerve cells cannot be regenerated using current methods,. “The challenge,” says Prof. Finberg, “is to slow down the disease, as well as to discover those at high risk as early as possible.”

In the video below,  Prof. Mandel gives an overview of her research the root causes of Parkinson's and Alzheimer's and how Azilect works.

Slowing down the course of the disease is exactly the focus of the professors’ research. Dopamine is broken down by an enzyme called monoamine oxidase type B (MAO-B). Azilect blocks this MAO-B enzyme, increasing the amount of dopamine.

For a newly diagnosed patient, Azilect alone prolongs the life of the existing dopamine and slows down the disease’s progression by up to several years. While patients will still lose dopamine-producing nerve cells, they will do so more slowly.  Patients at the more advanced stage of the disease where around 80 percent of the dopamine-producing nerve cells have died, will need to receive a combination of L-dopa —a molecule that is turned into dopamine by enzymes in the brain—and Azilect, to lengthen the dopamine’s lifespan.

Breakthroughs Don’t Happen Overnight

Profs. Youdim and Finberg have been studying the compound that Azilect is based on, Azilect, for more than 30 years. Prof. Youdim brought the compound with him when he arrived at the Technion in 1977 from England  and set up the Department of Pharmacology, where one of the first people he recruited was Prof. Finberg. Some 20 years ago, Prof. Youdim was approached by Dr. Ruth Levy, vice president of global innovative pipeline management at the Israeli pharmaceutical company Teva, to cooperate on creating a drug for Parkinson’s disease.

“It took 20 years!” exclaims Prof. Youdim, Director of the Eve Topf and US National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research and Teaching. Over the past decade, ATS funding has provided vital equipment and facilities for this research, as well as fellowships to support the recruitment of the best graduate students to work in the laboratories.

Dr. Levy is not surprised at how long the process took.  “It was really just an idea at that time,” she says. “This was the earliest stage that Teva has ever begun a collaboration to develop a drug from an existing compound.”  She added that drug development is a lengthy process; it never takes less than 12 years, and pharmaceutical companies assume that some two percent of their compounds will eventually make it to market. “We were lucky with Azilect,” she says.

Teva is currently conducting an 18-month clinical trial involving 1,000 newly-diagnosed, early-stage Parkinson’s patients at several dozen centers worldwide who have not yet received treatment.

(UPDATE: Phase III studies were successfully completed by Teva with all target points met. Click here to read the press release.)

“This is to corroborate our findings that if you start treatment earlier the drug not only improves symptoms but can affect the course of the disease and can really slow down its progression,” explains Dr. Levy.

Prof. Youdim's colleagues and students working in the Morris and Renee Rochlin Neuroprotective Drug Development Laboratory, in the Eve Topf Center, established with funding from ATS donors in Detroit, have found that Azilect has more extensive properties. “Azilect has neuroprotective-neurorescue activity,” he explains, “If you give it to animals, it protects nerve cells from dying and recent animal models of Parkinson's disease have shown that the drug has rescued and regenerated nerve cells that have already died.”  They have shown that these animals have the normal compliment of dopamine, similar to the control animals. This work appeared in Neurobiology of Disease.

While Prof. Youdim’s area of specialty is biochemistry, Prof. Finberg’s is in pharmacology and physiology, and it was his task to demonstrate that Azilect had no serious side effects. There is already a drug, deprenyl, used to treat Parkinson’s disease, which Prof. Youdim and his colleagues discovered in 1975, that blocks the MAO-B enzyme. However, deprenyl is converted in the brain into several types of amphetamines.

“This is potentially dangerous and toxic,” says Prof. Finberg. Azilect, while performing the same function, is chemically different and not converted into amphetamines and, therefore, has no such side effects.

Another benefit of Azilect says Prof. Youdim, is that  “it is 10 to 15 times more potent than deprenyl.”  This means that a patient has to take only one pill a day, making life easier for Parkinson’s patients who are usually taking several other medications simultaneously and often have difficulty swallowing because of their disease.

A Multitalented Compound

In collaboration with scientists at the Hebrew University, Prof. Youdim is now testing Azilect for potential treatment of another debilitating brain disorder, Alzheimer’s disease. The team is combining Azilect and a current anti-Alzheimer’s drug into one molecule.

A drug that has just one function simply isn’t enough, Prof. Youdim explains. “Diseases are complex. We need drugs that have multi-functional activities that can act on different sites in the brain. There is the first multi-functional drug, called ladostigil, for Alzheimer’s,” which is in Phase II clinical studies.

Prof. Youdim and his team have also discovered that Azilect, in one of its two forms, has significant cardiovascular protective properties, which they are investigating further.  In addition, one of the multifunctional drugs they are testing seems to be effective against diabetes, a disease also associated with the death of  cells.

Virtual Reality Device Helps People With Neurodegenerative Diseases Walk Normally 

Technion Prof. Yoram Baram has come up with a unique virtual reality device that can help people with Parkinson's, MS, or other neurodegenerative diseases walk with more ease and comfort. We invite you to watch the video and read the article below to learn about how this device changes the way people with these conditions literally look at walking.

More on this innovation below (from the Fall 2007 Technion USA Magazine)

“Healthy people have tools such as sensory feedback to tell them if they are using their muscles correctly,” explains Technion Computer Science Professor Yoram Baram. “This feedback is damaged in Parkinson’s and MS patients.” Such problems are also encountered by many elderly people. The simple act of walking can become a slow and frustrating guessing game.

sand footprints

To compensate for that damage, Baram’s Walkman-style invention actually measures walking motion, sending a beep through a small set of earphones with every step. That gives the wearer the feedback needed to assume a faster and steadier gait.

Meanwhile, a tiny eyepiece that clips onto the user’s glasses overlays what he or she is seeing with a bright virtual reality “floor.” Patients report feeling they’re more firmly on solid ground and can better navigate stairs, furniture and other obstacles in their path.

Already in use at several medical centers, the device is the first of its kind to respond to the wearer’s motions rather than simply provide a pre-set beat.

Read the press release, "Virtual Reality Helps MS Patients Walk Better."

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