Table 1.

Novel strategies in development for neuroimmune disease

Study	Target	Therapeutic class	Preclinical/clinical	Results
CD49d antisense drug ATL1102 reduces disease activity in patients with relapsing-remitting MS [16]	VLA4	ASO	Clinical–phase IIb ongoing (RRMS and SPMS)	Blocks expression of part of VLA4. 68% reduced Gd + lesions vs placebo.
Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy [28]	Arylsulfatase A	Lentiviral gene delivery to autologous hematopoietic stem cells	Clinical–phase I/II	Functional CSF enzyme replaced; prevented, improved or stabilized deficits
Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome [24]	WASP	Lentiviral gene delivery to autologous CD34+ cells	Clinical–phase I/II	Improved platelet count, reduced bleeding, reduced infection, eczema resolution, decrease in autoantibodies
Design of the first-in-human study of IONIS-MAPTRx, a Tau-lowering antisense oligonucleotide, in patients with Alzheimer disease [29]	MAPT	Antisense oligonucleotide (ASO)	Clinical–phase I ongoing	Tau reduction in brain, spinal cord, CSF (non-human primates). Clinical results pending.
Central and peripheral administration of antisense oligonucleotide targeting amyloid-β protein precursor improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (AβPPswe) mice [30]	APP	ASO	Preclinical	Reduced amyloid beta precursor protein and improved learning in mouse model of Alzheimer’s disease
Cell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes [31]	IL-10	Modified messenger RNA (mmRNA)	Preclinical	Increased IL10 production in leukocytes in IBD murine model
Gene therapy-induced antigen-specific Tregs inhibit neuroinflammation and reverse disease in a mouse model of multiple sclerosis [12]	MOG	AAV8 vector with hepatocyte promoter	Preclinical	Suppressed MOG-specific T effector cells in vitro. EAE and anti-MOG antibody response prevented in vivo.