Dr. David Arkadir, M.D., Ph.D. Neurology Department.
Parkinson's disease (PD) is a progressive degenerative disorder that is caused by the death of the dopamine-producing nerve cells in the brain. Its prevalence increases with age, affecting more than 1% of the population above the age of 60 years. Parkinson's disease symptoms include slowness of movements, muscle rigidity, tremors, and changes in speech and gait. Many patients also experience cognitive impairments, depression and anxiety. Currently, there is no disease-modifying drug that slows or reverses the progression of PD. Mannitol, an alcoholic sugar which has been approved by the Food and Drug Administration (FDA) as an osmotic diuretic agent and is a widely used, is a safe and inexpensive substance, and may change this reality.
Dr. David Arkadir, Senior Physician at the Parkinson’s disease and Movement Disorders Unit in the Department of Neurology at Hadassah intends to conduct the first of its kind Mannitol clinical trial to test if this inexpensive drug can be used for this incurable disease. He is inspired by the fact that experiments in animal models of PD revealed that Mannitol prevented neuronal death by reversing the accumulation of the toxic protein alpha-synuclein. In an alpha-synuclein transgenic fruit fly and mouse models (that express mutated alpha-synuclein in its cells), a robust reduction in α-synuclein deposits in the brains occurred after treatment, suggesting that Mannitol promotes α-synuclein clearance in the cell bodies. Remarkably, in the fly model the animals have regained lost motor function and have fully recovered from the disease.
Based on this preclinical work, numerous PD patients in Israel and worldwide started to take Mannitol on a regular basis. Many of these patients experienced subjective symptomatic benefits. However, in spite of the subjective therapeutic benefits of Mannitol in patients with PD, it has not been tested rigorously in the clinic and therefore there is a lack of objective data with regard to its efficacy. Thus, it is of utmost importance to collect the needed information on this drug in a controlled clinical trial, to gain information regarding the effectiveness and safety of Mannitol, and to produce scientific evidence that can be used to enhance the wellbeing of PD patients.
Dr. Arkadir, in collaboration with Prof. Segal from Tel Aviv University, is confident that this research will immensely contribute to recovery of PD patients. Dr. Arkadir seeks public and private funding - without support from the industry - to undertake this clinical trial for this incurable disease. More importantly, since Mannitol has been safely used for 60 years, the essential preclinical drug development steps that lead to a clinical drug would be very short. The support that Dr. Arkadir seeks for a controlled clinical trial to characterize safety and tolerability of oral Mannitol for PD patients is crucial, since no industry funds would be invested in a non-patentable substance. In fact, this could become the first disease-modifying drug to slow or reverse the progression of this devastating illness.
Dr. David Arkadir is a senior neurologist at Hadassah and the Hebrew University, specializing in Parkinson’s disease. He has extensive background in basic research and has served as principal investigator in a wide range of clinical trials involving PD. Prof. Segal is a molecular biologist at Tel Aviv University whose studies have demonstrated the positive effect of Mannitol on alpha-synclein in the laboratory and in animal models of PD.