Nanomedicine and lysosomal storage disorders

Lysosomal storage disorders (LSDs) are a group of ~50 genetic diseases of lysosomal function resulting in an intra-lysosomal accumulation of undegraded material with a combined incidence of 1:5.000 live births (Fuller et al. 2006). The clinical phenotype of LSDs varies widely from skeletal and visceral manifestation to severe CNS involvement depending on the defective protein and storage material involved.

Having attended the 8th European workshop and InNerMeD information Network on LSDs ( and the 13th international postgraduate course on LSDs, I had the chance to interact closely with clinicians working in this field and grasp the potential that new nanomedical systems bear.

Over 50% of LSDs have a neuropathology (Scriver et al. 2001) yet current treatment approaches such as enzyme replacement, substrate reduction therapy as well as gene and cell based strategies cannot target the central nervous system (CNS) since the blood brain barrier (BBB) imposes an insurmountable obstacle. The BBB is formed by brain endothelial cells with the support of pericytes and astrocytes, tightly regulating brain homeostasis and providing neuroprotection. Yet it is also the most significant factor limiting drug delivery to the CNS. Strategies for circumventing the BBB such as direct intracerebral injection or opening of the barriers tight junctions are considered highly invasive and lack specificity.

The use of nanoparticles for targeting the brain offers great potential for the
treatment of these neurodegenerative disorders and others. Injection of
nanoparticles into the blood stream which can be coupled with enzymes or other therapeutics allows wide-spread targeting of all brain regions given the exceptional vascular system of the brain. Yet various criteria for the design of such particles have to be kept in mind, amongst others: they have to be able to cross the BBB without reducing its integrity, allow linkage of enzymes or therapeutics, be internalized into neurons whilst maintaining their cargo and subsequently release it. Additionally the particle itself needs to be nonantigenic and biodegradable to have long term clinical relevance.

Initial attempts to use nanoparticles for LSD treatment have been made already, yet limited success emphasises the importance of understanding the molecular characteristics and functionality of the BBB first to allow for efficient nanoparticle design and BBB targeting.


Fuller et al. 2006:

Fuller M, Meikle PJ and Hopwood JJ, Epidemiology of lysosomal storage diseases: an overview. Oxford: Oxford PharmaGenesis; 2006

Scriver et al. 2001:
Scriver C, Beaudet A, Sly W, Valle D, Childs B, Kinzler K and Vogelstein B, The
metabolic and molecular bases of inherited disease. 8. New York: McGraw-Hill; 2001

Further reading:

David B, Pontikis CC and Scarpa M, Lysosomal storage diseases and the blood-brain barrier, Current Pharmaceutical Design; 2008

Muro S, New biotechnological and nanomedicine strategies for treatment of
lysosomal storage disorders. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010

Anne Iltzsche
PathChooser Fellow
Kings College London

Posted in Fellows Updates