Of create tight junctions between one another, roughly

Of the lysosomal storage diseases, more
than 50% affect the central nervous system (CNS) and these neuropathic symptoms
provide to be a complication for effective treatment; this is largely in part to
the blood-brain barrier (BBB), and cerebrospinal fluid (CSF) barrier (Bhaskar et al., 2010), shown in Figure 1. The BBB
is a semipermeable membrane which composed of a continuous layer of endothelial
cells. These cells create tight junctions between one another, roughly 1.2 nm
in size, and restricts the passage of molecules 400-600 Da or greater. Due to
these constraints, most small molecule drugs cannot penetrate this membrane to
act on astrocytes and pericytes which surround the membrane (Pardridge, 2007). The blood-CSF barrier acts similarly to keep
high molecular weight molecules out of the brain. The CSF acts as a sink for
larger radii molecules, with this effect increasing as molecular radius
increases (Laterra et al., 1999). Given these hurdles,
treating neuropathic symptoms can prove to be difficult in many treatment
methods.

 

Clinically approved treatments for LSDs include enzyme replacement therapy, substrate reduction therapy,
and hematopoietic stem
cell transplantation. Though these therapies effectively treat disease
affecting visceral organs, they remain relatively ineffective at treating
neurological insults. Furthermore, these methods seemingly only ameliorate
disease symptoms, effectively only managing the disease without truly ‘curing’
the underlying cause of lysosomal storage diseases. Alternative therapies including
gene therapy, nanoparticle-mediated delivery,
and combination therapy
take a different approach which work by correcting the genetic defect within
patients to provide a prolonged treatment. Some of these treatments show
promising results moving towards clinical trials; these methods and how they
aim to more effectively treat LSDs with neuropathic symptoms will be further
discussed in this document. 

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