Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON.

Effects of prolonged drought stress on Scots pine seedling carbon allocation.

As the number of drought occurrences has been predicted to increase with increasing temperatures, it is believed that boreal forests will become particularly vulnerable to decreased growth and increased tree mortality caused by the hydraulic failure, carbon starvation and vulnerability to pests following these. Although drought-affected trees are known to have stunted growth, as well as increased allocation of carbon to roots, still not enough is known about the ways in which trees can acclimate to drought. We studied how drought stress affects belowground and aboveground carbon dynamics, as well as nitrogen uptake, in Scots pine (Pinus sylvestris L.) seedlings exposed to prolonged drought. Overall 40 Scots pine seedlings were divided into control and drought treatments over two growing seasons. Seedlings were pulse-labelled with 13CO2 and litter bags containing 15N-labelled root biomass, and these were used to follow nutrient uptake of trees. We determined photosynthesis, biomass distribution, root and rhizosphere respiration, water potential, leaf osmolalities and carbon and nitrogen assimilation patterns in both treatments. The photosynthetic rate of the drought-induced seedlings did not decrease compared to the control group, the maximum leaf specific photosynthetic rate being 0.058 and 0.045 µmol g-1 s-1 for the drought and control treatments, respectively. The effects of drought were, however, observed as lower water potentials, increased osmolalities as well as decreased growth and greater fine root-to-shoot ratio in the drought-treated seedlings. We also observed improved uptake of labelled nitrogen from soil to needles in the drought-treated seedlings. The results indicate acclimation of seedlings to long-term drought by aiming to retain sufficient water uptake with adequate allocation to roots and root-associated mycorrhizal fungi. The plants seem to control water potential with osmolysis, for which sufficient photosynthetic capability is needed.