Irvine, CA (Feb 7, 2022) - Rubicon Biotechnology LLC is pleased to announce a grant award from the US Army Medical Research & Development Command (USAMRDC) to study Rubicon’s Rapid Recovery technology in cochlear cytoprotection. The project, titled “Rapid Delivery of Heat Shock Protein 72 for Auditory Cytoprotection After a Blast Exposure” is supported by the Assistant Secretary of Defense for Health Affairs and endorsed by the Department of Defense through the Hearing Restoration Research Program under Award No. W81XWH-21-2-0017. Rubicon is collaborating with several leading research institutions in the US on this program.
Auditory dysfunction, manifesting as hearing deficits, is the most prevalent neurosensory disability resulting from blast exposure. Studies at Walter Reed Army Institute Of Research (WRAIR) highlight the links between blast and auditory impairment. Based on published evidence that Hsp72 expression in the peripheral auditory system increases after a stress event, and plays a significant role in the cytoprotection of hair cells in the cochlea to attenuate axonal degeneration and cell death, we will be testing the Rapid Recovery drug technology at WRAIR in an animal model of cochlear blast injury.
Rubicon’s Rapid Recovery drug technology is a fusion protein called Fv-Hsp72 consisting of a cell penetrating antibody fragment attached to a human Hsp72 that has been structurally re-engineered to robustly withstand the protein damaging microenvironment surrounding injured tissues. Fv-Hsp72 has no competitors and will be a first-in-man drug. Our approach delivers Hsp72 directly into stressed and dying cells with greater speed than any conventional method, including gene induction. The superiority of our approach avoids the significant lag times (up to 72 hours) that occur when using a small molecule to induce Hsp72 production post-TBI. Placing therapeutic doses of exogenous human Hsp72 into the area of greatest injury within minutes also avoids the natural decrease in gene expression that occurs in older patients.
The studies in this grant include determining the duration of our drug in the auditory centers of the chinchilla brain using mass spectrometry. The chinchilla is a well-accepted model for studying auditory pathologies due to a hearing sensitivity and a frequency range that overlaps with humans. Fv-Hsp72 will be administered to animals starting 15 minutes after a moderately severe blast injury and thereafter in a repeat dosage scheme based on drug duration. Hearing loss will be monitored at 1, 7, 14 and 28 days post-blast, first by auditory brainstem response (ABR) to measure neural signals from the inner ear to the brain, then by distortion-product otoacoustic emission (DPOAE) to measure outer hair cell functioning. Upon completion of the 28 day study, animals will be sacrificed, cochlea extracted, decalcified and mounted for histological analysis. Inner and outer hair cell loss, along with the loss of synaptic connections to the cochlear nerve, will be quantified to determine if Fv-Hsp72 treatment results in significant reductions of anatomical auditory deficits after a blast injury.
“These proof-of-principle studies that show Fv-Hsp72 efficacy in treating hearing damage will complement our on-going studies and broaden the applicability of Fv-Hsp72 in the treatment of TBI-related injuries. Our long-term goal is the adoption of Fv-Hsp72 to treat a wide variety of traumatic tissue injuries both in military and civilian life.”, commented Dr. Missag H. Parseghian, Rubicon’s Founding Partner and CSO.
About Rubicon Biotechnology
Rubicon Biotechnology is a privately held biotechnology company that develops targeted, life-saving technologies in the areas of cardiology, neurology, ophthalmology and oncology. Rubicon has in-licensed two platform technologies for drug development. The first is Fv-Hsp72 from the Department of Veterans Affairs, which delivers heat shock protein 72, a key protein which saves injured cells suffering hypoxic and oxidative stresses that occur following common tissue injuries, such as heart attack, stroke and traumatic brain injury. The second technology, Modified Annexin A5, licensed from MosaMedix B.V., delivers tumor-targeted immunostimulants to enhance the immune system’s ability to fight cancer. Rubicon is developing these platform therapies with the goal of improving health outcomes and saving lives.
This work is supported by the Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, through the Hearing Restoration Research Program Focused Research Award Program Announcement under Award No. W81XWH2120017. Opinions, interpretations, conclusions and recommendations are those of Rubicon Biotechnology and are not necessarily endorsed by the Department of Defense. The award is administered by the US Army Medical Research Acquisition Activity, 839 Chandler Street, Fort Detrick MD 21702-5014.