DIRECT CNS DRUG DELIVERY
BEYOND THE SPINAL CANAL
MIR IMRANCHAIRMAN, INCUBE LABS, LLC
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CNS disorders afflict over 60 million Americans And nearly 1.5B worldwide
Costs for treating CNS diseases exceed $600B/year far more than any other group of diseases
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3M Americans suffer from Epilepsy50M people worldwide have the disease today
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5.4M Americans suffer from Alzheimer'sBy 2050, 16M will suffer from it
More than 26M worldwide have the disease today1 in 85 people globally
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More than 1M suffer from Parkinson's in the US
More than 7M patients worldwide have the disease
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400,000 Americans suffer from Multiple Sclerosis
2.5M worldwide have the disease
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20M Americans live with Depression
121M people worldwide suffer from the disease
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Despite Staggering Numbers, Drug Treatments Remain Limited
Toxicity and Serious Adverse Events are the Major Causes of Drug Failure
Serious Peripheral Side Effects Limit the Use of Powerful CNS Drugs
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• Oral or injectable delivery of CNS drugs can result in serious adverse side effects
The Problem with Systemic Delivery of CNS Drugs
• Powerful large molecules and biologics cannot be delivered systemically
• Patient compliance is a huge issue with many CNS disorders
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• Reduces or eliminates peripheral side effects of potent CNS drugs
• Allows for transport of large drug molecules across the BBB
• Solves the issue of patient compliance
Intracranial or Intrathecal Delivery of Therapeutic Agents Using an Implantable
Drug Delivery System
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• BBB transport limitations with protein/antibody based therapies will likely require direct central delivery
• Acetylcholine esterase inhibitors: could deliver drugs such as revastigmine intracranially
• Addresses 2 key issues with this class of drugs:• Compliance – major issue with Alzheimer's patients• Peripheral effects – muscle weakness, cramps,
gastrointestinal effects, etc. associated with this class of drugs
Alzheimer’s
• GDNF: intracranial delivery overcomes inability to penetrate BBB
• Apomorphine: the most effective known dopamine agonist, yet currently can not be used due to systemic effects
• Intracranial drug delivery addresses key issues with this class of drugs
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Parkinson’s Disease
• Several therapeutic approaches, but efficacy is still limited:• Interferons (e.g., beta interferon (Avonex))
• Hormonal (e.g., adrenocorticotrophic hormone)
• Immunological (e.g., monoclonal antibodies such as natalizumab (Tysabri))
• Gene Therapy (viral vectors, nucleotide/nucleoside therapeutics)
• Central delivery allows us to optimize efficacy of existing drugs
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Multiple Sclerosis
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• Monoamine Oxidase Inhibitors (MAOIs): currently, black-box warnings due to side effects
• Intracranial delivery of MAOIs eliminates these issues
• Enhanced efficacy – ability to titrate therapeutic levels of drug without causing peripheral side effects (hypertensive episodes)
• Addresses compliance – a major issue with Depression patients
Depression
• Doxorubicin, etoposide: offer limited efficacy due to low brain penetration of major chemotherapeutic agents
• Intracranial delivery enables maintenance of high levels of chemotherapeutic agents, while minimizing systemic toxicity
• No serious peripheral adverse effects leading to increased therapeutic ratio
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Oncology – Gliomas