Therapeutic antibodies targeting antigens in the central nervous system (CNS) are of high interest for a number of neurological diseases and have gained significant momentum as a potential treatment strategy for several CNS disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain cancer. However, drug delivery to the CNS for antibodies and other macromolecules has thus far proven challenging due to the presence of the blood-brain barrier at all the CNS blood vessels. Here we examined the effects of a neurite growth-enhancing anti-Nogo A antibody therapy following 3 routes of administration – intrathecal (i.e. directly into the cerebro-spinal fluid), intravenous, and subcutaneous – after large photothrombotic cerebral strokes in adult rats. Intrathecal treatment of full-length IgG anti-Nogo A antibodies enhanced recovery of the stroke-impaired forelimb grasping function, whereas intravenous or subcutaneous antibody administration had no detectable effect on stroke recovery in spite of large amounts of antibodies in the peripheral circulation. Thus, in contrast to intravenous and subcutaneous delivery, intrathecal administration is an effective and reliable way to target CNS antigens with therapeutic antibodies. Our data reveal that antibody delivery to the CNS is far from trivial. While intrathecal application is feasible and guarantees defined antibody doses in the effective range for a biological function, the identification and establishment of easier, peripheral body routes of administration remains an important task to facilitate antibody-based future therapies of CNS disorders.
Link to full article: https://link.springer.com/article/10.1007%2Fs13311-020-00864-z