Low dose naltrexone therapy in multiple sclerosis

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Summary

The use of low doses of naltrexone for the treatment of multiple sclerosis (MS) enjoys a worldwide following amongst MS patients. There is overwhelming anecdotal evidence, that in low doses naltrexone not only prevents relapses in MS but also reduces the progression of the disease. It is proposed that naltrexone acts by reducing apoptosis of oligodendrocytes. It does this by reducing inducible nitric oxide synthase activity. This results in a decrease in the formation of peroxynitrites, which in turn prevent the inhibition of the glutamate transporters. Thus, the excitatory neurotoxicity of glutamate on neuronal cells and oligodendrocytes via activation of the α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid class of glutamate receptor is prevented. It is crucial that the medical community respond to patient needs and investigate this drug in a clinical trial.

Introduction

Multiple sclerosis (MS) affects thousands of sufferers worldwide. In many cases it is characterized by the relentless progression of disease with increasing disability. Treatment with interferons or with glatiramer acetate necessitates multiple weekly or daily injections, and this can be associated with significant side effects. Furthermore, the drugs are only moderately effective in reducing relapses, while the progression of disease is not much affected [1], [2]. Thus, there is a need for newer therapeutic or neuroprotective agents in MS. The lack of highly effective drugs for MS, may in part reflect the considerable debate regarding the etiology and pathogenesis of MS. There are suggestions in the literature that the widely used animal model of experimental allergic encephalitis may not fully reflect human MS [3], [4], [5], [6].

Section snippets

Apoptosis and oxidative damage in multiple sclerosis

Recent work by Barnett and Prineas [4], [5], [6], [7] confirms previous reports and suggests that the developing lesion in MS brains, lacks the inflammatory cells. Instead it shows apoptosis of oligodendrocytes and microglial activation as the prominent pathological finding. Multiple studies have implicated apoptotic pathway components in the pathogenesis of MS [8], [9], [10]. There is considerable evidence that the cause of the oligodendrocyte cell apoptosis, demyelination and axonal damage in

Low dose naltrexone in multiple sclerosis

While there are no scientific studies documenting the effects of low dose naltrexone (LDN) therapy in MS, the related drug naloxone has been investigated in a variety of neurodegenerative and inflammatory disorders such as septic shock, injuries to brain and spinal cord, myocardial and cerebral stroke and Alzheimer’s disease [15]. There is however considerable anecdotal evidence supporting the use of LDN in MS by the lay public.

Anecdotal literature from the United Kingdom and the United States

Hypothesis

The peroxynitrites produced by astrocytes and microglial cells inhibit the glutamate transporters in synaptic clefts of neuronal cells and adjacent oligodendrocytes resulting in excitatory glutamate neurotoxicity. It is postulated that naltrexone acts by reducing nitric oxide synthase activity. This results in a decrease in the formation of peroxynitrites, which in turn prevents the inhibition of the glutamate transporters. Thus, the excitatory neurotoxicity of glutamate on neuronal cells and

Testing the hypothesis

This new hypothesis may be tested in the following manner:

  • (1)

    It is known that peroxynitrites as well as glutamic acid levels are elevated in the CSF of patients with MS [16]. The biochemical basis of LDN therapy can therefore be tested by measuring the levels of glutamic acid and peroxynitrites before and then 3–6 months after the start of LDN therapy. A positive response to LDN will be seen by observing the decrease in CSF glutamic acid and peroxynitrite levels following LDN treatment.

  • (2)

    Since the

Conclusion

The use of LDN has gained widespread public acceptance, inspite of the lack of enthusiasm from prescribing physicians. It is incumbent upon us to investigate this drug, for it offers the potential of an oral therapy for MS with few side effects. At the very least, by showing a lack of efficacy, patients can be persuaded from using LDN in lieu of the standard therapies of MS.

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