Successful Delivery of Apomorphine to the Brain Following Intranasal Administration Demonstrated in Clinical Study
New Approach to Treatment of Central Nervous System Diseases Bypasses the Blood - Brain - Barrier
HAUPPAUGE, N.Y., July 18 /PRNewswire/ -- Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK - news) announced today that it has demonstrated the preferential uptake of intranasally administered Apomorphine directly into the cerebral spinal fluid (CSF), a fluid that surrounds and supports the brain and spinal cord. The nasal delivery of pharmaceutically active compounds that are not able to cross the blood-brain-barrier when given by other routes of administration may provide a new, non-invasive way of treating Alzheimer's disease, Parkinson's disease, stroke and other important brain diseases and conditions.
The study, which was initiated in May, was conducted as a Phase I, single dose, open label clinical trial in 12 healthy male subjects at SUNY Stony Brook Medical Center in Stony Brook, New York. Apomorphine was administered intranasally to each subject, and thereafter blood was drawn, and CSF samples were obtained by spinal tap. Apomorphine levels were determined by HPLC-MS- MS, a state-of-the-art analytical tool. The results were expressed as a ratio of CSF level to blood level at various times indicated. The data indicate that Nastech's intranasal Apomorphine HCl formulation produced a CSF to plasma ratio of 0.27 to 0.44 at 20 minutes. This can be compared to a ratio of less than 0.05 resulting from the subcutaneous administration of Apomorphine under the same experimental conditions as noted in published clinical studies. No significant adverse events were observed during the study.
The results of the clinical study are promising because distribution of drugs to the brain tissue is highly restricted even though the brain receives approximately 20% of cardiac output. Drugs normally reach the central nervous system (CNS) via two mechanisms: the brain capillaries and the CSF. The endothelial cells of the brain's capillaries, which appear to be more tightly joined to one another than are those of other capillaries, contribute to the fact that many drugs enter the brain slowly or not at all. In addition to the restrictive capillary walls, there are also connective tissue cells that form an astrocyte sheath close to the basement membrane of the capillary endothelium. Together the capillary walls and the astrocytic sheath form what is commonly referred to as the blood-brain-barrier. The results of the clinical study indicate that certain drugs via nasal administration may be deposited directly into the CSF, bypassing the blood-brain-barrier.
``We are pleased by the results of this clinical study, which confirms that nasal drug delivery, unlike other drug delivery modalities, provides a unique pathway for drug molecules to reach the brain,'' stated Steven C. Quay, M.D., Ph.D., Chairman, President and Chief Executive Officer of Nastech. ``We intend to expand our internal research programs and the breadth of our therapeutic focus to include intranasal delivery of drugs to potentially treat major diseases of the central nervous system, such as Parkinson's, Alzheimer's and Multiple Sclerosis. We also believe this provides unique intellectual property opportunities that should enhance Nastech's valuable patent estate.''
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I don't know if the properties of apomorphine assist the results, but if not this is impressive I think?
Wilder |
