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Transspinal delivery of drugs by transdermal patch back-of-neck for Alzheimer's disease: a new route of administration.

Discovery Medicine 2019 January
NSAIDs may prevent Alzheimer's disease (AD) but have failed as a treatment, possibly because only 1-2% of an oral NSAID dose reaches the brain. This minuscule dose is enough to have a preventative effect on Alzheimer's disease but not to treat it. We propose a new route of administration for drugs to treat AD: transspinal delivery by transdermal patch over the back-of-neck/cervical spine. The drug would diffuse from the patch through the intervertebral spaces, penetrate the dura, enter the CSF, and reach the brain. For example, diclofenac from a transdermal patch over the back of neck should readily penetrate the dura mater to reach the CSF and brain; since the analgesic ziconotide, and antisense molecules for treating spinal muscular atrophy in children and Huntington's disease, are delivered intrathecally and readily enter the brain. In addition to NSAIDs, an anticancer drug, paclitaxel, has considerable potential as an AD treatment. Paclitaxel is administered IV. But the blood-brain penetration of paclitaxel is poor and paclitaxel has systemic side effects such as anemia, leukopenia, peripheral neuropathy, etc. A high dose of paclitaxel might be administered to the brain by transdermal patch over the back of the neck/cervical spine while avoiding the systemic side effects. A transdermal patch over the cervical spine could revolutionize the drug therapy of AD, and probably other neurodegenerative/neuropsychiatric diseases as well.

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