ND0612 (levodopa/carbidopa for subcutaneous infusion) in patients with Parkinson's disease and motor response fluctuations: A randomized, placebo-controlled phase 2 study.

Introduction: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system under development for patients with Parkinson's disease (PD) and motor fluctuations.

Methods: This was a randomized, placebo-controlled, double-blind, 2-period study evaluating the safety and pharmacokinetics of ND0612 in PD patients on an optimized oral levodopa regimen and experiencing ≥2 h/day of OFF time. During Period-1, patients received their current standard of care (SoC) levodopa/carbidopa and were randomized (2:1) to 14 days treatment with adjunct ND0612 (daily levodopa/carbidopa dose of 270/63 mg) or placebo infusion +SoC.

Novel evolutionary-conserved role for the activity-dependent neuroprotective protein (ADNP) family that is important for erythropoiesis.

Background: ADNP is vital for embryonic development. Is this function conserved for the homologous protein ADNP2?

Results: Down-regulation/silencing of ADNP or ADNP2 in zebrafish embryos or mouse erythroleukemia cells inhibited erythroid maturation, with ADNP directly associating with the β-globin locus control region.

Conclusion: ADNPs are novel molecular regulators of erythropoiesis.

The "alternative" choice of constitutive exons throughout evolution.

Alternative cassette exons are known to originate from two processes-exonization of intronic sequences and exon shuffling. Herein, we suggest an additional mechanism by which constitutively spliced exons become alternative cassette exons during evolution. We compiled a dataset of orthologous exons from human and mouse that are constitutively spliced in one species but alternatively spliced in the other.