The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial

Brain Research Bulletin

2015

Section: Discussionmentioning

confidence: 96%

Improved clinical behavior of established relapsing-remitting experimental autoimmune encephalomyelitis following treatment with endogenous opioids: Implications for the treatment of multiple sclerosis

Hammer

Brain Research Bulletin

2015

“…Information on the length of confirmed MS, as well as the length of time on either Copaxone or LDN, was provided by the patient, and not documented by medical records. 5 ]-enkephalin and b-endorphin concentrations Human serum samples were analyzed using five ELISA kits for [Met 5 ]-enkephalin and one human b-endorphin kit. Serum [Met 5 ]-enkephalin levels for all MS and non-MS patients are presented in Figure 1(a).…”

Section: Ms Patient Demographicsmentioning

confidence: 99%

Featured Article: Serum [Met⁵]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone

Ludwig

2017

Exp Biol Med (Maywood)

This report presents human and animal data identifying a novel biomarker for the onset and progression of multiple sclerosis (MS). Humans diagnosed with MS have reduced serum levels of OGF (i.e. [Met 5 ]-enkephalin) relative to non-MS neurologic patients, and low-dose naltrexone (LDN) therapy restored their enkephalin levels. Serum OGF levels were reduced in mice immunized with MOG 35-55 prior to any clinical behavioral sign of experimental autoimmune encephalomyelitis, and LDN therapy restored their serum OGF levels. b-endorphin concentrations were not altered by LDN in humans or mice. Thus, blood levels of OGF may serve as a new, selective biomarker for the progression of MS, as well as response to therapy. AbstractLow-dose naltrexone is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. The mechanism underlying low-dose naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple sclerosis is, in part, intermittent blockade of opioid receptors followed by upregulation of endogenous opioids. Short, intermittent blockade by naltrexone specifically blocks the opioid growth factor receptor resulting in biofeedback events that increase production of the endogenous opioid growth factor (OGF) (chemically termed [Met 5 ]-enkephalin) facilitating interactions between opioid growth factor and opioid growth factor receptor that ultimately, result in inhibited cell proliferation. Preclinical studies have reported that enkephalin levels are deficient in animal models of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. Our hypothesis is that serum enkephalin levels are diminished in humans with multiple sclerosis and experimental autoimmune encephalomyelitis mice, and that change in serum opioid growth factor levels may serve as a reasonable candidate biomarker for the onset of experimental autoimmune encephalomyelitis and response to therapy. To address this, we designed a two-part study to measure endogenous opioids in multiple sclerosis patients, and to investigate the temporal pattern of decline in serum enkephalin concentrations in mice with chronic progressive experimental autoimmune encephalomyelitis and treated with low-dose naltrexone. For comparison, we investigated whether low-dose naltrexone exposure in normal mice also resulted in altered enkephalin levels.In both animal models, we monitored tactile and heat sensitivity, as well as differential white blood cell counts as indicators of inflammation. Serum [Met 5 ]-enkephalin levels were lower in humans with multiple sclerosis relative to non-multiple sclerosis patients, and low-dose naltrexone restored their levels. In experimental autoimmune encephalomyelitis mice, [Met 5 ]-enkephalin levels were depressed prior to the appearance of clinical disease, and were restored with low-dose naltrexone treatment. Low-dose naltrexone therapy had no effect on serum [Met 5 ]-enkephalin or b-endorphin in normal mice. Thus, [Met 5 ]-enkephalin (i.e. opioid growth factor)...

show abstract

“…However, the financial burden of individual therapy can range upward to $60K annually (37), and side effects still reduce compliance and thereby overall efficacy (38). Randomized clinical trials of enkephalins or LDN are limited (40)(41)(42)(43), possibly because use of LDN has been reported to have a few side effects, and large pharmaceutical companies are not interested in sponsoring studies on a repurposed drug (i.e., LDN) that is already FDA approved at substantially higher dosages. Nonetheless, there remains a need for safe, effective treatments that are alternatives to the β-interferon products.…”

Section: Clinical Studiesmentioning

confidence: 99%

Endogenous Opioids in the Etiology and Treatment of Multiple Sclerosis

Multiple Sclerosis: Perspectives in Treatment and Pathogenesis

2017