Gene Delivery into the Central Nervous System (CNS) Using AAV Vectors

Application of gene therapies is a promising approach to the treatment of various neurological disorders, including Parkinson\u27s disease, amyotrophic lateral sclerosis (ALS), and lysosomal storage disorders, which are not treatable by any other means. However, the blood–brain barrier (BBB) is a key obstacle to gene delivery to the central nervous system (CNS). Adeno-associated virus (AAV) vectors have emerged as a promising tool for gene delivery to the CNS, thanks to their safety and ability to transduce non-dividing neuronal cells. In this chapter, we discuss strategies for delivering genes across the BBB, focusing especially on potential routes of administration of AAV vectors and promising applications of AAV vectors to the treatment of CNS disorders

Neonatal Gene Therapy for Inherited Disorders

In spite of developments of neonatal intensive care medicine, it is still difficult or impossible to treat several inherited genetic disorders using conventional pharmacological methods. Gene therapy is a promising alternate approach for treating a variety of genetic disorders. By the time the patient reaches adulthood, however, it is often too late for effective treatment. But in several of these cases, neonatal gene therapy appears potentially useful against inherited disorders that are not obviously treatable through any other methods. This chapter describes the strategy for neonatal gene therapy for inherited disorders and presents preclinical neonatal gene therapy data for two inherited disorders, metachromatic leukodystrophy and hypophosphatasia. We also discuss the utility, advantages, problems and potential of neonatal gene therapy for inherited disorders

Possible Excitonic Phase of Graphite in the Quantum Limit State

The in-plane resistivity, Hall resistivity and magnetization of graphite were investigated in pulsed magnetic fields applied along the \textit{c}-axis. The Hall resistivity approaches zero at around 53 T where the in-plane and out-of-plane resistivities steeply decrease. The differential magnetization also shows an anomaly at around this field with a similar amplitude compared to that of de Haas-van Alphen oscillations at lower fields. This transition field appears insensitive to disorder, but reduces with doping holes. These results suggest the realization of the quantum limit states above 53 T. As a plausible explanation for the observed gapped out-of-plane conduction above 53 T, the emergence of the excitonic BCS-like state in graphite is proposed.Comment: 15 pages, 6 figures, to be published in J. Phys. Soc. Jp

Thermodynamic Investigation of Metamagnetism in Pulsed High Magnetic Fields on Heavy Fermion Superconductor UTe2_2

We investigated the thermodynamic property of the heavy fermion superconductor UTe$_2$ in pulsed high magnetic fields. The superconducting transition in zero field was observed at $T_{\rm c}$=1.65 K as a sharp heat capacity jump. Magnetocaloric effect measurements in pulsed-magnetic fields obviously detected a thermodynamic anomaly accompanied by a first-order metamagnetic transition at $\mu$$_{0}$$H_{\rm m}$=36.0 T when the fields are applied nearly along the hard-magnetization $b$-axis. From the results of heat capacity measurements in magnetic fields, we found a drastic diverging electronic heat capacity coefficient of the normal state $\gamma$$_{\rm N}$ with approaching $H_{\rm m}$. Comparing with the previous works via the magnetic Clausius-Clapeyron relation, we unveil the thermodynamic details of the metamagnetic transition. The enhancement of the effective mass observed as the development of $\gamma_{\rm N}$ indicates that quantum fluctuation strongly evolves around $H_{\rm m}$; it assists the superconductivity emerging even in extremely high fields.Comment: 6 pages, 6 figures, accepted for publication in JPS