Introduction Carbon nanotubes (CNT) have recently been studied as novel and versatile drug and gene delivery vehicles. When CNT are suitably functionalized, they can interact with various cell types and are taken up by endocytosis. Areas covered Anti-cancer drugs cisplatin and doxorubicin have been delivered by CNT, as well as methotrexate, taxol and gemcitabine. The delivery of the antifungal compound amphotericin B and the oral administration of erythropoietin have both been assisted using CNT. Frequently, targeting moieties such as folic acid, epidermal growth factor or various antibodies are attached to the CNT-drug nanovehicle. Different kinds of functionalization (e.g., polycations) have been used to allow CNT to act as gene delivery vectors. Plasmid DNA, small interfering RNA and micro-RNA have all been delivered by CNT vehicles. Significant concerns are raised about the nanotoxicology of the CNT and their potentially damaging effects on the environment. Expert opinion CNT-mediated drug delivery has been studied for over a decade, and both in vitro and in vivo studies have been reported. The future success of CNTs as vectors in vivo and in clinical application will depend on achievement of efficacious therapy with minimal adverse effects and avoidance of possible toxic and environmentally damaging effects.

SARM1, a protein with critical NADase activity, is a central executioner in a conserved programme of axon degeneration. We report seven rare missense or in-frame microdeletion human SARM1 variant alleles in patients with amyotrophic lateral sclerosis (ALS) or other motor nerve disorders that alter the SARM1 auto-inhibitory ARM domain and constitutively hyperactivate SARM1 NADase activity. The constitutive NADase activity of these seven variants is similar to that of SARM1 lacking the entire ARM domain and greatly exceeds the activity of wild-type SARM1, even in the presence of nicotinamide mononucleotide (NMN), its physiological activator. This rise in constitutive activity alone is enough to promote neuronal degeneration in response to otherwise non-harmful, mild stress. Importantly, these strong gain-of-function alleles are completely patient-specific in the cohorts studied and show a highly significant association with disease at the single gene level. These findings of disease-associated coding variants that alter SARM1 function build on previously reported genome-wide significant association with ALS for a neighbouring, more common SARM1 intragenic single nucleotide polymorphism (SNP) to support a contributory role of SARM1 in these disorders. A broad phenotypic heterogeneity and variable age-of-onset of disease among patients with these alleles also raises intriguing questions about the pathogenic mechanism of hyperactive SARM1 variants.

We fine mapped the leukocyte antigen (HLA) region in 13,770 Parkinson’s disease (PD) patients, 20,214 proxy-cases, and 490,861 controls of European origin. Four HLA types were associated with PD after correction for multiple comparisons, HLA-DQA1*03:01, HLA-DQB1*03:02, HLA-DRB1*04:01, and HLA-DRB1*04:04. Haplotype analyses followed by amino acid analysis and conditional analyses suggested that the association is protective and primarily driven by three specific amino acid polymorphisms present in most HLA-DRB1*04 subtypes—11V, 13H, and 33H (OR = 0.87, 95% CI: 0.83–0.90, p < 8.23 × 10−9 for all three variants). No other effects were present after adjustment for these amino acids. Our results suggest that specific HLA-DRB1 variants are associated with reduced risk of PD, providing additional evidence for the role of the immune system in PD. Although effect size is small and has no diagnostic significance, understanding the mechanism underlying this association may lead to the identification of new targets for therapeutics development.

Introduction It is 23 years since carbon allotrope known as carbon nanotubes (CNT) was discovered by Iijima, who described them as “rolled graphite sheets inserted into each other”. Since then, CNTs have been studied in nanoelectronic devices. However, CNTs also possess the versatility to act as drug- and gene-delivery vehicles. Areas covered This review covers the synthesis, purification and functionalization of CNTs. Arc discharge, laser ablation and chemical vapor deposition are the principle synthesis methods. Non-covalent functionalization relies on attachment of biomolecules by coating the CNT with surfactants, synthetic polymers and biopolymers. Covalent functionalization often involves the initial introduction of carboxylic acids or amine groups, diazonium addition, 1,3-dipolar cycloaddition or reductive alkylation. The aim is to produce functional groups to attach the active cargo. Expert opinion In this review, the feasibility of CNT being used as a drug-delivery vehicle is explored. The molecular composition of CNT is extremely hydrophobic and highly aggregation-prone. Therefore, most of the efforts towards drug delivery has centered on chemical functionalization, which is usually divided in two categories; non-covalent and covalent. The biomedical applications of CNT are growing apace, and new drug-delivery technologies play a major role in these efforts.