Function, structure and quality of striated muscles in the lower extremities in patients with late onset Pompe Disease:an MRI study

Background Pompe Disease (PD) is a rare inherited metabolic myopathy, caused by lysosomal-α-glucosidase (GAA) deficiency, which leads to glycogen accumulation within the lysosomes, resulting in cellular and tissue damage. Due to the emergence of a disease modifying treatment with recombinant GAA there has been a large increase in studies of late onset Pompe Disease (LOPD) during the last decade. Methods The present study evaluates muscle quality in 10 patients with LOPD receiving treatment with enzyme replacement therapy and in 10 age and gender matched healthy controls applying T1-weighted Dixon MR imaging and isokinetic dynamometry. Muscle quality was determined by muscle strength in relation to muscle size (contractile cross-sectional area, CSA) and to muscle quality (fat fraction). A follow-up evaluation of the patients was performed after 8–12 months. Patient evaluations also included: six-minute walking test (6MWT), forced vital capacity, manual muscle testing and SF-36 questionnaire. Results Fat fraction of knee flexors (0.15 vs 0.07, p < 0.05) and hip muscles (0.11 vs 0.07, p < 0.05) were higher in patients than controls. In patients, contractile CSA correlated with muscle strength (knee flexors: r = 0.86, knee extensors: r = 0.88, hip extensors: r = 0.83, p < 0.05). No correlation was found between fat fraction and muscle strength. The fat fraction of thigh muscles did not correlate with scores from the clinical tests nor did it correlate with the 6MWT. During follow-up, the contractile CSA of the knee extensors increased by 2%. No other statistically significant change was observed. Quantitative MRI reflects muscle function in patients with LOPD, but larger long-term studies are needed to evaluate its utility in detecting changes over time

The Effect of Cannabis-Based Medicine on Neuropathic Pain and Spasticity in Patients with Multiple Sclerosis and Spinal Cord Injury: Study Protocol of a National Multicenter Double-Blinded, Placebo-Controlled Trial

Disease or acquired damage to the central nervous system frequently causes disabling spasticity and central neuropathic pain (NP), both of which are frequent in multiple sclerosis (MS) and spinal cord injury (SCI). Patients with MS and SCI often request treatment with cannabis-based medicine (CBM). However, knowledge about effects, side effects, choice of active cannabinoids (Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) alone or in combination), and doses of CBM remains limited. Using a double-blind, parallel design in a national multicenter cohort, this study examines the effect of CBM on spasticity and NP. Patients are randomized to treatment with capsules containing either THC, CBD, THC and CBD, or placebo. Primary endpoints are patient-reported pain and spasticity on a numerical rating scale. Other endpoints include quality of life and sleep, depression and anxiety, and relief of pain and spasticity. Side-effects of CBM are described. In a sub-study, the pharmacodynamics (PD) and pharmacokinetics (PK) of oral capsule CBM are examined. We expect that the study will contribute to the literature by providing information on the effects and side-effects of CBD, THC, and the combination of the two for central neuropathic pain and spasticity. Furthermore, we will describe the PD/PK of THC and CBD in a patient population

Pharmacokinetics and pharmacodynamics of cannabis‐based medicine in a patient population included in a randomized, placebo‐controlled, clinical trial

Abstract Information on the pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered cannabis‐based medicine (CBM) in capsule formulation in patient populations is sparse. In this exploratory study, we aimed to evaluate the PK and PD in a probable steady state of CBM in neuropathic pain and spasticity in a population of patients with multiple sclerosis (MS). Of 134 patients participating in a randomized, double‐blinded, placebo‐controlled, trial, 23 patients with MS (17 female) mean age 52 years (range 21–67) were enrolled in this substudy. They received oral capsules containing Δ9‐tetrahydrocannabinol (THC, n = 4), cannabidiol (CBD, n = 6), a combination (THC&CBD, n = 4), or placebo (n = 9). Maximum doses were 22.5 mg (THC) and 45 mg (CBD) a day divided into three administrations. PD parameters were evaluated for pain and spasticity. Blood samples were analyzed using an ultra‐high‐performance liquid chromatography–tandem mass spectrometer after protein precipitation and phospholipid removal. PK parameters were estimated using computerized modeling. The variation in daily dose and PK between individuals was considerable in a steady state, yet comparable with previous reports from healthy controls. Based on a simulation of the best model, the estimated PK parameters (mean) for THC (5 mg) were Cmax 1.21 ng/mL, Tmax 2.68 h, and half‐life 2.75 h, and for CBD (10 mg) were Cmax 2.67 ng/mL, Tmax 0.10 h, and half‐life 4.95 h, respectively. No effect was found on the PD parameters, but the placebo response was considerable. More immediate adverse events were registered in the active treatment groups compared with the placebo group