Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2-3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this study was to develop a protocol to determine the proper dosage of Mecasin. METHODS: This is a phase II-A, multi-center, randomized study with three arms. Thirty-six patients with ALS will be randomly assigned to one of three groups, each receiving the standard treatment with 100 mg of riluzole in addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes include results of the Short Form Health Survey-8, Medical Research Council Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function test, forced expiratory volume in 1 s and its ratio to forced vital capacity, creatine kinase, and body weight. The frequencies of total adverse events and serious adverse events will be described and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Gwangju and Sanbon Hospital (2016-5-4 and 2016-34-01, respectively). An Investigational New Drug status (30731) was granted by the Korea Food and Drug Administration. DISCUSSION: This trial will aim to identify the optimal dosage of Mecasin. Additionally, it will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS. TRIAL REGISTRATION: Korean National Clinical Trial Registry CRIS; KCT0001984 . Registered on 28 July 2016.

The Use of Korean Medicine to Treat Patients with Spinobulbar Muscular Atrophy, Kennedy's Disease - A Case Study.

OBJECTIVES: Studies involving patients with spinobulbar muscular atrophy (SBMA), which is often referred to as Kennedy's disease, similar to those involving patients with progressive muscular disease (PMD), are rare. This paper reports a case study involving the use of Korean medicine to treat a patient with SBMA. METHODS: We treated a patient with SBMA with unique symptoms by using various kinds of pharmacopuncture and herbal medicines for about two and a half years. After the treatment had ended, we evaluated the patient's conditions and the side effects of the treatment. RESULTS: After treatment, the patient's symptoms were stabilized, and the patient suffered no abnormalities or side effects. No special changes in condition were noted during treatment period, and the patient was very satisfied with his response to treatment. CONCLUSION: Existing treatments have some considerable after effects and are difficult to apply in domestic clinics. In this regard, our findings should open possibilities for new clinical guidelines. Nevertheless, the limitations associated with this case study should be resolved, and more studies need to be conducted.

Study on the Single Dose Toxicity of ShinEumHur Pharmacopuncture Injected into the Muscles of Rats.

OBJECTIVES: This study was carried out to analyze the single dose toxicity of ShinEumHur (SEH) pharmacopuncture injected into the muscles of Sprague-Dawley rats. METHODS: The SEH pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (K-GMP). After the mixing process with sterile distilled water had been completed, the pH was controlled to between 7.0 and 7.5. All experiments were conducted at Biotoxtech, an institution authorized to perform non-clinical studies under the Good Laboratory Practice (GLP) regulations. Sprague-Dawley rats were chosen for the pilot study. Doses of SEH pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. We examined the survival rate, weights, clinical signs, mean hematology parameters, mean clinical chemistry, necropsy and histopathological findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. RESULTS: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. CONCLUSION: The above findings suggest that treatment with SEH pharmacopuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

A 4-week Repeated dose Oral Toxicity Study of Mecasin in Sprague-Dawley Rats to Determine the Appropriate Doses for a 13-week, Repeated Toxicity Test.

OBJECTIVES: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. METHODS: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. RESULTS: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/ kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. CONCLUSION: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively.

Yangkyuk-Sanhwa-Tang induces changes in serum cytokines and improves outcome in focal stroke patients.

Yangkyuk-Sanhwa-Tang (YS-Tang), a specific prescription composed of nine herbal mixtures, has been developed as a formula for the Soyangin cerebral infarction (CI) patients according to Sasang constitutional philosophy. However, the mechanisms by which this formula affects CI remain unknown. This study revealed changes in cytokine production in the acute stage of Soyangin constitution CI patients after YS-Tang administration. Clinical signs (vertigo, headache and slurred speech) of CI disappeared significantly in about 2 weeks after oral administration of YS-Tang (P < .05). The mean interleukin (IL)-2 plasma levels were lower by 15% in the patients with CI than in the normal groups, whereas the mean TNF-alpha, IL-4, IL-6 and IgE levels were significantly higher in the patients (P < .01). There were no significant differences in interferon-gamma (IFN-gamma) levels between the groups. Serum IFN-gamma and IL-2 levels were elevated significantly (P < .01) in the patients with CI by YS-Tang administration. Significant reduced plasma levels (P < .01) of TNF-alpha, IL-4, IL-6 and IgE were observed in the patients treated with YS-Tang. During the period of YS-Tang administration, there were no other adverse effects. The data indicate that YS-Tang has an enhancing effect on antiinflammatory cytokines and an inhibitory effect on inflammatory cytokines. These results may implicate a good CI treatment effect of YS-tang and that its action may be due to regulation of cytokine production.

Effect of geumgoeshingi-whan pharmacopuncture on the blood pressure in spontaneously hypertensive rats.

OBJECTIVE: The aim of this experiment was to investigate the effect and the mechanism of Geumgoeshingi-whan (GGSGW) Pharmacopuncture at the acupoint GV 4 on the blood pressure in spontaneously hypertensive rats (SHR). METHODS: SHR were injected with normal saline solution (Control-SHR group)or GGSGW Pharmacopuncture (GGSGW-SHR group) at the acupoint GV 4. The systolic arterial blood pressure and renal parameters were measured for two weeks. RESULTS: The systolic arterial blood pressure was decreased significantly after GGSGW Pharmacopuncture at the acupoint GV 4 in SHR, followed by a significant rise in creatine clearance. The plasma levels of aldosterone were decreased significantly after GGSGW Pharmacopunctureas were the plasma levels of atrial natriuretic peptide (ANP). CONCLUSION: These results suggest that the blood pressure was decreased significantly after GGSGW Pharmacopuncture at the acupoint GV 4 in SHR and that the depressor response of the blood pressure was related to decreases in the plasma levels of aldosterone and ANP.

Study of Single-dose Toxicity of Aconitum Kusnezoffii Reichb. Pharmacopuncture in Rats.

OBJECTIVE: This study was performed to analyze the singledose toxicity of Aconitum kusnezoffii Reichb. pharmacopuncture (AKRP). METHODS: All experiments were conducted at the Korea Testing & Research Institute (KTRI), an institute authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Twenty (20) Sprague-Dawley rats were chosen for the pilot study. The animals were divided into four groups of five animals per group: group 1 (G1) being the control group with each animal receiving an injection of 0.3 ml of saline and groups 2, 3, and 4 (G2, G3, and G4) being the experimental groups with each animal receiving an injection of 0.1, 0.2 or 0.3 ml of AKRP, respectively. This study was conducted with the approval of the Institutional Animal Ethics Committee. RESULTS: No deaths occurred in any of the 4 groups, and the LD50 of AKRP administered via IV was higher than 1.77 ml/kg. Some changes in the weights of the male rates were observed between the control group and the experimental groups, but no significant differences were noted in the weights of the female rats. To check for abnormalities in organs and tissues, we stained representative sections of each specified organ with Hematoxylin & Eosin for light microscopic examination. The results showed no significant differences in any of the organs or tissues. CONCLUSIONS: The above findings suggest that Aconitum kusnezoffii Reichb. pharmacopuncture is a relatively safe treatment. Further studies on the subject should be conducted to yield more concrete evidence.

Acupuncture and spontaneous regression of a radiculopathic cervical herniated disc.

The spontaneous regression of herniated cervical discs is not a well-established phenomenon. However, we encountered a case of a spontaneous regression of a severe radiculopathic herniated cervical disc that was treated with acupuncture, pharmacopuncture, and herb medicine. The symptoms were improved within 12 months of treatment. Magnetic resonance imaging (MRI) conducted at that time revealed marked regression of the herniated disc. This case provides an additional example of spontaneous regression of a herniated cervical disc documented by MRI following non-surgical treatment.

Regulation of TH1/TH2 cytokine production by Chungsim-Yeunja-Tang in patients with cerebral infarction.

Chungsim-Yeunja-Tang is a prescription for the Taeumin cerebral infarction (CI) patients according to Sasang constitutional philosophy. Taeumin patients with CI were treated with CY-Tang during the acute stage. Clinical signs of CI disappeared markedly in about 2 weeks after oral administration of CY-Tang in all patients. The mean interleukin (IL)-2 plasma levels were slightly lower in the patients with CI than in the normal groups, whereas the mean TNF-alpha, IL-4, IL-6, and IgE levels were significantly higher in the patients with CI. There were no significant differences in interferon-gamma (IFN-gamma) levels between the groups. Serum IFN-gamma and IL-2 levels derived from (Th) 1 cells were significantly elevated in the patients with CI by CY-Tang administration. Significant reduced plasma levels of IL-4 and IL-6 derived from Th2 cells and IgE were observed in the patients treated with CY-Tang. Plasma levels TNF-alpha derived from Th1 significantly increased in the patients treated with CY-Tang. During the period of CY-Tang administration, there were no other adverse effects. The data indicate that CY-Tang has a good CI treatment effect, and that its action may be due to the regulation of cytokine production.