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CMCC 2008

Delivery of Therapeutic Compounds Across the Blood Brain Barrier

Inventors: Manjunath Narasimhaswamy, Priti Kumar, Premlata Shankar

Invention Types: Therapeutics

Research Areas: Neurology/Neuroscience, Oncology/Hematology

Keywords: CNS, Drug Delivery, Transfection

For More Information Contact:  Dietz, Ryan

 

Invention Description:

Delivery of therapeutic compounds to the Central Nervous System (CNS) is complicated by the presence of the blood brain barrier (BBB). Various brain endothelial cells form this highly specialized structure that tightly regulates the transport of molecules from the bloodstream into the brain.


Traditionally, the only technique available for bypassing this membrane involves disruption of the BBB. However, disruption has proven to be minimally effective and often results in appreciable levels of non-specific entry of neurotoxic molecules. The most common alternative, direct injection, is invasive, high risk, and results in limited dispersal of the therapeutic. To address this problem, Dr. Narasimhaswamy and colleagues have developed a novel delivery method allowing for noninvasive, intravenous, transvascular delivery of therapeutic compounds, including biologics, to the brain. The technology utilizes a peptide isolated from the rabies virus (RVG-9r) which has also been shown to increase the amount and efficacy of compounds already known to cross the BBB. Recent work using this technology has shown suppression of neuroinflammation by targeted delivery of siRNAs to macrophages in the CNS.

Applications:

• The technology provides a proprietary method to cross the blood-brain barrier and enable the delivery of therapeutic compounds.|
• Improved delivery and therapeutic efficacy of molecules already known to cross the BBB.

Competitive Advantages:

• Noninvasive, intravenous, transvascular delivery of large molecules across the BBB.

• Deeper, more uniform distribution of delivered therapeutics to the brain compared to traditional techniques.

• The technology may be used for the transport of all major therapeutic classes including small molecules, siRNA, shRNA, antibodies, proteins, DNA and other biologics.

Business Opportunity:

Nonexclusive or exclusive license

Key Publications: The technology provides a proprietary method to cross the blood-brain barrier and,
enabling delivery for small-molecule, peptides, antibodies, DNA for gene-therapy,
siRNA, shRNA and imaging agents. In addition, this technology includes a reagent
allowing for neuronal cell transfection.

Related Publications: Kumar P, Wu H, McBride JL, Jung K-E, Kim MH, Davidson BL, Lee S, Shankar P, Manjunath N, 2007. Transvascular Delivery of Small Interfering RNA to the Central Nervous System. Nature 448: 39-43.

Kim S-S, Ye C, Kumar P, Chiu I, Subramanya S, Wu H, Shankar P, Manjunath N, 2010.Targeted delivery of siRNA to macrophages for anti-inflammatory treatment. Mol. Ther.18(5): 993-1001.

Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011 Apr;29(4):341-5.

Conceiçäo M, Mendonça L, Nóbrega C, et al.Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Macado-Joseph disease neurological phenotype. Biomaterials. 2016 Mar;82:124-37.

IPStatus: Patented