pharmacological treatment of a rare genetic disease: n-acetylcysteine in myopathy associated selenoprotein n-related myopathy (sepn1-rm)

Conditions: Selenoprotein N-related Myopathy

Summary: the objective of this study is to determine whether the administration of n-acetylcysteine (nac) improves oxidative stress. to determine this, the study will assess the impact of oral treatment on the balance between reduced and oxidized form of glutathione in erythrocytes of peripheral blood.

a prospective, monocentric, crossover, double-blind, placebo-controlled study. for each patient the study will be divided in two treatment periods of 6 months separated by a 2 month washout period. 24 patients will be randomized in two groups, one group treated first with placebo during 6 months, followed by 6 months; the second group treated in the reverse sequence, then placebo. 24 healthy volunteers will also be enrolled in the study in order to collect reference values for biochemical biomarkers. d-1: run-up visit, patients will be hospitalized in intensive care unit to collect information about diet, physical activity and smoking. during follow-up visits: we will analyze the impact of treatment with n-acetylcysteine (nac) on: * biomarkers of redox homeostasis, * measures of locomotor functional capacity, * body mass composition, * respiratory functional abilities. biomarkers that reflect the status of antioxidant defense mechanisms, parameters that reflect the cell damage to oxidative stress, the markers of inflammation and metabolic alterations induced by oxidative stress, body composition in terms of lean mass and fat mass, the motor functional abilities, respiratory function capabilities, will be compare before and after treatment. these measures could complement the information on the status of oxidative stress and clarify the effects of n-acetylcysteine (nac) on the evolution of the disease in these patients. the correlation of biomarker measurements in muscle and systemic tissues will be checked. furthermore we will collect information about the lifestyle through standardized questionnaires that include diet, smoking, and habitual physical activity. environmental factors and lifestyle can influence the balance oxidant / antioxidant patients and contribute to the variability of the clinical severity of the disease.

Eligibility criteria:
inclusion criteria: 1. for patients: * patient \>18 and \<60 years old * patients with selenoprotein n-related myopathy with homozygous or compound heterozygous mutations in the gene sepn1-rm * informed written consent * patients capable of being followed up throughout the duration of the study * patient trained in the use of cough assist * patients having an health insurance * patient accepting to commit not to introduce major changes in diet and lifestyle during the study period 2. for healthy volunteers: * volunteers \>18 and \<60 years old * informed written consent * health insurance exclusion criteria: 1. for patients: * pregnancy * intolerance to n-acetylcysteine (nac), galactose or fructose; malabsorption glucose or galactose; lactase deficiency * consumption of synthetic vitamins, nac and other antioxidants within 3 months prior to inclusion * treatment with corticosteroids or non-steroidal anti-inflammatory from time to time in the 4 weeks preceding the inclusion or for more than 3 days between 12 and 4 weeks before inclusion * planned surgery within 3 months before inclusion or during the inclusion period * intercurrent or existing illnesses such as chronic infectious diseases (hiv, hepatitis, etc.), asthma, malignant tumor pathology, hematological pathology * expected survival less than 14 months * inability to understand the instructions or the implications of the protocol 2. for healthy volunteers: * pregnancy * consumption of synthetic vitamins, nac and other antioxidants within 3 months prior to inclusion * treatment with corticosteroids or non-steroidal anti-inflammatory from time to time in the 4 weeks preceding the inclusion or for more than 3 days between 12 and 4 weeks before inclusion * planned surgery within 3 months before inclusion or during the inclusion period * intercurrent or existing illnesses such as chronic infectious diseases (hiv, hepatitis, etc.), asthma, malignant tumor pathology, hematological pathology * inability to understand the instructions or the implications of the protocol * bleeding disorders or other bleeding risks or risk of infection.

Keywords: selenoprotein n-related myopathy biomarkers washout n-acetylcysteine