Growth hormone potentiates thyroid hormone effects on post-exercise phosphocreatine recovery in skeletal muscle.

International audienceOBJECTIVE: The aim of the study was to determine the respective impact of thyroxine and growth hormone on in vivo skeletal mitochondrial function assessed via post exercise phosphocreatine recovery. DESIGN: The hind leg muscles of 32 hypophysectomized rats were investigated using (31)P nuclear magnetic resonance spectroscopy at rest and during the recovery period following a non tetanic stimulation of the sciatic nerve. Each rat was supplemented with hydrocortisone and was randomly assigned to one of the 4 groups: the group Hx was maintained in hypopituitarism., the group HxT was treated with 1 μg/100g/day of thyroxine (T4), the group HxG with 0.2 IU/kg/day of recombinant human GH (rGH) and the group HxGT by both thyroxine and rGH. Inorganic phosphate (Pi), phosphocreatine (PCr) and ATP were directly measured on the spectra, permitting the calculation of the phosphorylation potential (PP). RESULTS: At rest, the rats treated with rGH or T4 exhibited higher PCr levels than rats Hx. The recovery rates of PCr and PP were higher in rats treated with T4 than in T4-deprivated rats, suggesting improved mitochondrial function. The rats treated by both T4 and rGH showed higher PCr and PP recovery than those maintained in hypopituitarism or treated with T4 or rGH alone. CONCLUSIONS: The study demonstrates that in contrast to T4, GH given alone in hypophysectomized rats does not improve in vivo mitochondrial oxidative metabolism. Growth hormone potentiates T4 effects on oxidative metabolism

Real-life effectiveness 1 year after switching to avalglucosidase alfa in late-onset Pompe disease patients worsening on alglucosidase alfa therapy: A French cohort study

International audienceIntroductionLate-onset Pompe disease (LOPD) is characterized by a progressive myopathy resulting from a deficiency of acid α-glucosidase enzyme activity. Enzyme replacement therapy has been shown to be effective, but long-term treatment results vary. Avalglucosidase alfa demonstrated non-inferiority to alglucosidase alfa in a phase 3 study, allowing in France compassionate access for advanced LOPD patients unresponsive to alglucosidase alfa.MethodsData from the French Pompe registry were analyzed for patients who benefited from a switch to avalglucosidase alfa with at least 1 year of follow-up. Respiratory (forced vital capacity [FVC]) and motor functions (Six-Minute Walk Test [6MWT]) were assessed before and 1 year after switching. Individual changes in FVC and 6MWT were expressed as slopes and statistical analyses were performed to compare values.ResultsTwenty-nine patients were included (mean age 56 years, 11 years of prior treatment). The FVC and 6MWT values remained stable. The individual analyses showed a stabilization of motor worsening: –1 m/year on the 6MWT after the switch versus –63 m/year the year before the switch (i.e., a worsening of 33%/year before vs. an improvement of 3%/year later). Respiratory data were not statistically different.DiscussionAt the group level, gait parameters improved slightly with a stabilization of previous worsening, but respiratory parameters showed limited changes. At the individual level, results were discordant, with some patients with a good motor or respiratory response and some with further worsening.ConclusionSwitching to avalglucosidase alfa demonstrated varied responses in advanced LOPD patients with failing alglucosidase alfa therapy, with a general improvement in motor stabilization

Effect of enzyme replacement therapy with alglucosidase alfa (Myozyme (R)) in 12 patients with advanced late-onset Pompe disease

International audienceThe efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT in a cohort of patients with severe Pompe disease.We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared.Twelve patients (7 males) were identified. Median age at symptom onset was 24years [IQR=15.5; 36.0]. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24h [IQR=21.88; 24.00] (min 20; max 24). ERT was initiated at a median age of 52.5years [IQR=35.75; 66.50]. Median treatment duration was 55months [IQR=39.5; 81.0]. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90min and two increased their assisted walking distance, by 80 and 20m.Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities