Executive Summary - Dermal and Pulmonary RNAi / PSR
The Drug:
The small molecule localizes where applied, readily crosses cell membranes, and binds with high affinity to the peptidyl transferase site on ribosomes, restricting translation of RNA into proteins in a dose dependent manner (RNAi / PSR). The therapeutic effect of this full spectrum RNAi / PSR is anti-proliferative, antiviral, and anti-inflammatory activity, which may be maintained for 3 consecutive days without a reduction in cell viability, after which time apoptosis induction increases proportionately with the duration of the regimen. The compound is intracellularly inactivated in around half a day, requiring at least twice daily administration for continuous activity.
Therapeutic Effect:
Antiproliferative: The antiproliferative attributes of the drug were well characterized in human clinical trials against cancer. The drug is not well suited for intravenous administration because of its blood insolubility and rapid, non specific, cellular internalization, however it is exceptionally well suited for topical and inhalable administration for exactly the same reasons. The drug is a G1 and G2 phase cytostatic. Apoptosis can be induced, if desired, by prolonged administration (for several days or more).
Antiviral: The antiviral activity of the drug was demonstrated, ex vivo, in virally infected human cells. The data demonstrated full spectrum viral protein synthesis inhibition and inhibition of virus progeny DNA synthesis as a secondary effect of RNAi / PSR. Viruses require use of host ribosomes as they lack the genome to create their own ribosomes. Inhibiting host ribosomes inhibits replication of viruses that require use of host ribosomes.
Anti-Inflammatory: The anti-inflammatory activity of RNAi / PSR was demonstrated in vivo in mouse models. The dermis contains mast cells, macrophages, and lymphocytes. Animal model data suggests that inhibiting this part of the immune response with topical RNAi / PSR can reduce inflammation by 44%.
Localization: Human skin studies showed > 97 % dermal retention by topical application. Any drug entering the blood is readily metabolized by the liver.
Exceptional Safety: The therapeutic dermal and pulmonary doses are hundreds of times smaller than the systemic human No Observable Effect Level (NOEL) dose by intravenous infusion.
Markets Targeted / Market Advantages
We are targeting dermal and pulmonary indications where localization and/or dual action activity would be therapeutically desirable. Localization provides systemic safety by delivering the drug only where it is needed. Dual action provides a better treatment option.
Dermal and Pulmonary Intellectual Property - Issued US Patents
Psoriasis Treatment Method (Topical)
Epidermal Exfoliation Method (Topical)
Apoptotic Chemosurgery (Interstitial)
Pulmonary Anti-Inflammatory (Inhalable)
COPD Treatment Method (Inhalable)
Pending: Dual Action Dermal and Pulmonary Anti-Infective / Anti-Inflammatory.
DISCLAIMER AND IMPORTANT NOTICE: The Compositions and Methods presented on this website are all in preclinical stages. They are based only on our understanding of the proposed underlying mechanisms of action and on any available coincidental corroborative empirical evidence, any of which may in fact turn out not to be correct, or may be prevented from functioning as envisioned because of other factors or mechanisms of action not contemplated or considered, or may even cause harm because of factors or mechanisms of action not anticipated. The process of obtaining FDA approvals has not been started in any of the areas disclosed on this website. The disclosures here are purely for scientific information exchange purposes, representing one scientific point of view, and are not intended to suggest, or be used for, any proposed medical treatments.
© 2010 Mark Zamoyski & NexGen Biomedical, Inc.