Current perspectives on intrathecal drug delivery

Abstract

Advances in intrathecal analgesia and intrathecal drug delivery systems have allowed for a range of medications to be used in the control of pain and spasticity. This technique allows for reduced medication doses that can decrease the side effects typically associated with oral or parenteral drug delivery. Recent expert panel consensus guidelines have provided care paths in the treatment of nociceptive, neuropathic, and mixed pain syndromes. While the data for pain relief, adverse effect reduction, and cost-effectiveness with cancer pain control are compelling, the evidence is less clear for noncancer pain, other than spasticity. Physicians should be aware of mechanical, pharmacological, surgical, and patient-specific complications, including possible granuloma formation. Newer intrathecal drug delivery systems may allow for better safety and quality of life outcomes.

Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases

“…ASOs lack the ability to cross the blood brain barrier, a limitation that was initially considered an exclusion for their use as a therapeutic approach for neurodegenerative diseases. However, in the clinical setting, multiple drugs including chemotherapies, some spasticity medications, and pain medications are routinely delivered to the CSF that circulates throughout the CNS (Bottros and Christo, 2014). Despite the prediction that highly charged ASOs would remain localized to the site of CSF infusion, empiric data strikingly show widespread distribution throughout the brain and spinal cord in mice (DeVos et al, 2013; Kordasiewicz et al, 2012; Lagier-Tourenne et al, 2013; Passini et al, 2011), rats (Smith et al, 2006), and non-human primates (Kordasiewicz et al, 2012; Passini et al, 2011; Rigo et al, 2014; Smith et al, 2006) using intraventricular or intrathecal injection.…”

Management of Neuroinflammatory Responses to AAV-Mediated Gene Therapies for Neurodegenerative Diseases

“…An additional disadvantage of this administration route for CNS disorders is that delivering large amounts of virus into the An ICV injection consists of delivering the drug directly into the CSF through the lateral ventricles providing the broadest CNS distribution. Although this technique is relatively safe and effective, and is routinely undertaken by neurosurgeons [75], it is not without risks and complications including infections, intracerebral hemorrhage, subcutaneous CSF leaks and increased intracranial pressure [75][76][77][78]. However, these rare complications are most often associated with chronic delivery of biologics, and single-delivery AAV treatments will likely be safer.…”

Intrathecal delivery of frataxin mRNA encapsulated in lipid nanoparticles to dorsal root ganglia as a potential therapeutic for Friedreich’s ataxia

“…If FXN LNPs are efficacious by intrathecal administration, it is possible that injections would only be required once a month or less often, given the slow decay in mFXN and the ability of cells to tolerate an excess amount of FXN without yielding a deleterious effect. Although such an approach would be invasive, given the requirement for repeat administration, intrathecal catheters connected to surgically implanted reservoirs that can be refilled with a therapeutic agent are currently being developed 40 , which may minimize the risks associated with administration. Altogether, this study provides a method that enables recombinant mRNA delivery in the form of nanoparticles to DRG for disease treatment, such as in the case of FRDA and spinal muscular atrophy 41 , or for other applications.…”