Abstract
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease affecting the central nervous system (CNS). The damage caused to the neurons disrupts the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and, sometimes, psychiatric problems. There is increasing evidence that a combination therapy will be necessary to achieve a significant slowing of MS progression.
In this study, we will test - in vivo in a specific mouse model of MS - the efficacy of the small-molecular weight compound proliferation-inducing ligand (APRIL) in modulating the known myelination-inhibitory effects within MS, combined with a new device for their transcranial delivery. At first, we aim to assess the efficacy of the immune-modulating protein APRIL against de-myelination and inflammation, in vivo and longitudinally with Magnetic Resonance Imaging (MRI) within the Cuprizone mouse model of MS. In parallel to this, we aim to test the biocompatibility and transcranial delivery efficacy of a new delivery system (a modified Ommaya reservoir device - OM pod) developed within the Marie Skłodowska-Curie-PMSMatTrain consortium. Finally, we will evaluate longitudinally the efficacy of the combined APRIL OM pod-delivery to reduce inflammation and demyelination in vivo in the Cuprizone mouse model of MS. Such critically delivery of the therapeutics released from the hydrogel would represent a step change in the approach for treating MS.
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