Journal of Alzheimers & Neurodegenerative Diseases Category: Clinical Type: Review Article
Intrathecal Melatonin Administration via Implanted Pump for Treatment of Alzheimer’s Disease and Other Neurodegenerative Disorders: A Mechanical Pineal Gland Strategy
- Nestor D Tomycz1*
- 1 Department Of Neurological Surgery, Allegheny General Hospital, Pittsburgh, United States
*Corresponding Author:Nestor D Tomycz
Department Of Neurological Surgery, Allegheny General Hospital, Pittsburgh, United States
Received Date: Feb 19, 2018 Accepted Date: Apr 18, 2018 Published Date: May 04, 2018
Decades of research has supported those human neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and cerebellar ataxias share in common severe oxidative and free radical damage to the brain. In fact, there is an abundance of evidence that oxidative stress is the ultimate trigger for apoptosis and neuronal cell death in such diseases.The brain has a complex anti-oxidant system which has evolved to constantly scavenge detrimental free radicals and reactive oxygen species and it has been long proposed that much of cognitive decline associated with aging may be linked with progressive oxidative damage to neurons. However, strategies to treat the shared pathologic endgame of these diseases, regardless of etiology, as a brain redox problem have been lacking. Anti-oxidant treatment strategies in human neurodegenerative diseases have repeatedly focused on oral or parenteral administration, which are likely hampered by the blood brain barrier from significantly “reducing” the central nervous system. Here I review the evidence to support a study of intrathecal melatonin for disease modification and neuroprotection in the neurodegenerative disorders such as Alzheimer’s disease.
Intrathecal pump delivery of melatonin, one of nature’s oldest and most potent central nervous system free radical scavengers and anti-oxidants may prove beneficial in the treatment of various neurodegenerative disorders including Alzheimer’s disease.
OXIDATIVE STRESS AND NEURODEGENERATIVE DISEASES
MELATONIN AND NEURODEGENERATIVE DISEASES
WHY INTRATHECAL DELIVERY?
Melatonin is a powerful free radical scavenger and antioxidant which is secreted by the pineal gland into the cerebrospinal fluid. Despite passing readily through the blood brain barrier, the bioavailability of oral melatonin is poor and variable [36,37]. Melatonin is safe even at high doses but delivery via an intrathecal pump would more closely mirror the physiologic endogenous delivery of melatonin in humans. Another great benefit of intrathecal pump delivery is the programmable option which could permit CSF delivery of melatonin only during evening hours, similar to the physiologic pineal-secreted delivery of melatonin - a mechanical pineal gland strategy. The flex-dose programming of available intrathecal pumps (Synchromed II, Medtronic, Inc.) could allow continuous delivery of melatonin into the CSF for multiple hours during just the evening, which may reduce side effects such as alteration of circadian rhythms. This synergy of a safe and powerful endogenous CSF anti-oxidant and a well-established, implantable and programmable human CSF delivery system would take advantage of biomimicry and would not require the extensive safety testing required for novel small molecules or proteins engineered for the treatment of neurodegenerative diseases.
The neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease share oxidative damage to the brain in their pathophysiology. The age-related decrease in cerebrospinal melatonin - an important central nervous system anti-oxidant system - may predispose the brain to age-related cognitive decline and neurodegenerative processes. Augmenting the CSF melatonin concentration in a nocturnal temporal manner via implantable intrathecal pump and catheter system is a simple and novel strategy for disease modification in the neurodegenerative disorders and deserves clinical trial.
CONFLICT OF INTEREST
The author reports no conflict of interest.
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Citation:Tomycz ND (2018) Intrathecal Melatonin Administration via Implanted Pump for Treatment of Alzheimer’s Disease and Other Neurodegenerative Disorders: A Mechanical Pineal Gland Strategy. J Alzheimers Neurodegener Dis 4: 016.
Copyright: © 2018 Nestor D Tomycz, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.