Although it is coined a 20th century predicament, Parkinson’s disease was actually first discovered in 19th century London by Doctor James Parkinson. Yet even two centuries later, researchers and doctors are still grappling for an explanation as to what causes this neurodegenerative disease that inflicts 500,000 new Americans each year.
In what continues to be a medical mystery, Israeli researchers have made breakthrough progress in the race to discover the origin and detect a cure for this quickly spreading condition. NoCamels spoke to three Israeli researchers who have made it their life goal to discover the neurological secrets behind Parkinson’s disease.
1. Israel: a living laboratory for the study of Parkinson’s
Professor Nir Giladi, Director of the Neurology Department of Tel Aviv Sourasky Center, starts off by explaining that Parkinson’s disease is a multi-dimensional disorder that develops later in life, but which can in many cases be detected early on using genetic patterns.“We know today that environmental factors as well as lifestyle and genetics influence the development of Parkinson’s disease,” Giladi tells NoCamels. He points out that according to various studies, “Among Ashkenazi Jews [of European origin], 35 percent of Parkinson’s patients have developed the disorder due to known genetic mutations. This is the highest percentage in any population worldwide, making Israel a unique living laboratory for understanding Parkinson’s disease.”
Due to the large volume of Parkinson’s patients living in Israel, about 20,000 according to rough estimates, researchers like Giladi have been able to create a method of tracking the genetic likelihood of the neurodegenerative condition spreading within a family group. Once a patient is officially diagnosed with Parkinson’s disease, the center asks for permission to get in touch with his or her immediate relatives, “This way, we can follow people at risk. Every year we have a handful of people who were considered healthy when they were initially examined, but became Parkinson’s patients later on.”
In his research, Giladi found that people who contract some of the early stage symptoms of the disease, which include slowness of movement, rigidity and a resting tremor, compensate the performance of the brain because the individual is forced to use other networks in order to keep functioning normally. While this makes sense, it is also part of the reason why Parkinson’s patients are often diagnosed only 30 years after they actually contract the neurological condition: “The concept of healthy versus sick is becoming vague because we have now very sensitive tools to detect abnormalities. We can test people who seem perfectly healthy and detect subtle but important changes.” These changes can, for example, be seen in an arm swing, walking patterns (known as gait) or the way the brain solves problems.
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Giladi emphasizes that Parkinson’s is a multi-faceted disease that influences things like mood, cognition, sexual function, sensation, vision and even smell, which is why, in his opinion, treatment of the condition should also be adaptable: “Israel is pioneer in the interdisciplinary treatment of Parkinson’s. Here at our center we have neurologists, nurses, physiotherapists, occupational therapists, speech and language pathologists, social workers, sexologists and orthopedists working with patients. All of these factors are directly involved in the treatment of a single patient because of the varied problems they face.”
2. A blood test to diagnose Parkinson’s symptoms early on
When she was still a doctoral student, Dr. Ronit Sharon, Associate Professor and Chairwoman of the Department of Biochemistry and Molecular Biology at the Hebrew University of Jerusalem, became interested in explaining how Parkinson’s disease deteriorates the function of neurons in the brain. Sharon’s early start made her a pioneer in the field of neuronal degeneration, driven by the disturbing conclusion that, “By the time Parkinson’s is diagnosed, 70 percent of the patient’s neurons are already gone, and once they are gone we cannot recover them.”
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Sharon is part of a team of researchers that has been working for decades to discover a biomarker that will help doctors clearly recognize Parkinson’s disease in their patients as early as possible. Their goal is to develop blood tests that will diagnose the conditions in its earliest stages, even before the physical symptoms of rigidity, tremors and memory loss are able to have an effect.
Sharon’s team’s efforts have paid off; they discovered a protein called alpha-synuclein that is heavily present in the brain’s neurons. Together they were able to show that the alpha-synuclein at the tips of our nerve cells interacted or failed to interact with brain lipids in certain ways that could produce the death of neurons and the neurodegenerative characteristics of Parkinson’s disease. She hopes that her team’s discovery on the relationship between alpha-synuclein and brain lipids will be implemented as part of a simple blood test to detect Parkinson’s disease early on, without the tedious task of examining each patient’s family history. “The goal is to have a test that will show that people carry Parkinson’s disease even when they don’t feel it yet. We want to understand what is the earliest trigger of the chain of events from where on neurons will start degenerating.”
3. The search for a miracle drug
Professor Emeritus Moussa Youdim in the Department of Molecular Pharmacology at the Technion-Israel Institute of Technology is trying to understand the molecular mechanisms behind complex and mysterious neurodegenerative diseases like Parkinson’s, but from the perspective of treatment, not diagnosis. Youdim stresses that a major problem with treatment is that there is no available drug that can modify the course of the condition and induce neurorestoration, or the recovery of neurons, once the disease has significantly progressed.
Youdim explains that the majority of drugs being used to treat Parkinson’s today are merely treating the symptoms, and not the disease itself: “It is like taking aspirin against a toothache, it does not change anything about the tooth and few hours later we have to take the next pill. We are trying to develop drugs that are not only neuroprotective, but can also slow down the progression of cell death and ultimately modify the disease by inducing neurorestoration.” Born in Tehran and educated in the United States, Youdim’s research into an effective treatment for Parkinson’s is conducted in conjunction with his role as Director of the Eve Topf and National Parkinson Foundation Centers for Excellence for Neurogenerative Diseases Research and Teaching.
Instead of discovering why Parkinson’s patients neurons die out, Youdim wants to stop it from happening, completely. He has developed what he calls a “very promising drug” that will hopefully protect neurons from dying, modify the destructive path of the disease in the brain and possibly even restore neurons. Youdim’s studies into specific enzymes in the brain, called monoamine oxidase A and B, and their functions, led to the formulation of Selegiline, one of the most efficient drugs for the early treatment of Parkinson’s disease, until he developed an even better drug called Azilect. After extensive testing on animal and cellular models of the disease, Azilect has proven successful in restoring dopamine neurons that previously died out with neurodegeneration.
Despite Azilect’s success on the market following FDA approval, Youdim, much like Giladi, understands that neurodegenerative diseases are multi-dimensional and that drugs need to be developed accordingly: “We know that Parkinson’s is a very complex disease with effects on multiple mechanisms of neurodegenerative processes and several pathological consequences. We are developing drugs that aim at targeting all of them.” While Youdim’s super-drug is no where close to being ready, he hopes it will be able to tackle the multifaceted aspects of the disease and reverse some of the tough neurological, physical and emotion damage.