Hyaluronidase for prevention, treatment, reduction and/or abolishment of cerebral edema and intracranial pressure

This technology proposes the use of hyaluronidase, an enzyme that targets hyaluronic acid, as a pharmacological treatment to reduce complications and improve prognosis after traumatic brain injury.

Unmet Need: Pharmacological treatment that addresses the underlying cause of brain edema

Traumatic brain injury (TBI) is one of the leading causes of death worldwide, and injury-induced brain edema can contribute to significant increases in intracranial pressure (ICP), which is a primary indicator of poor outcome following TBI. Fixed negative charge molecules are exposed in brain tissue following injury and attract positive ions into the tissue, leading to an increase in osmotic pressure. Current treatments to manage ICP following TBI include systemic administration of the hyperosmotic agents, mannitol and hypertonic saline, hyperventilation, barbiturate coma, and decompressive craniectomy. However, each of these interventions are associated with adverse effects, and their efficacy is still a major topic of debate, highlighting the need for treatments with better outcomes.

The Technology: Hyaluronidase administration for treatment of cerebral edema following TBI

This technology proposes the use of hyaluronidase, which forms an anchor for many highly charged glycosaminoglycans, as a pharmacological therapeutic to minimize brain swelling following TBI. Importantly, in the case of severe TBI where a mass lesion occurs due to swelling, this treatment may lessen the need for surgical evacuation of the lesion or may be used in combination to decrease the potential for additional swelling. Administration of hyaluronidase immediately following TBI decreases the fixed charge density in brain tissue and reduces swelling in both in vitro and in vivo models of brain edema. The treatment can be administered directly into the brain or in combination with existing methods to allow the enzyme to cross the blood brain barrier. This technology has potential to significantly improve outcomes following TBI with minimal complications and is compatible with current clinical strategies, such as systemic hypertonic saline or mannitol, to control brain swelling.

This technology reduced brain tissue swelling in vitro and in an in vivo mouse model of TBI. The treatment decreased the fixed charge density in brain tissue as measured by the DMMB assay. Additionally, administration of hyaluronidase in vivo reduced brain edema in a mouse model of TBI measured by the wet/dry weight method and by magnetic resonance imaging.

Applications:

• Pharmacological treatment for reducing brain swelling and relieving ICP after TBI
• Pharmacological treatment for brain tissue damaged by stroke or ischemic attack
• Pharmacological treatment for post-operative swelling
• Pharmacological treatment of ICP induced by brain tumor

Advantages:

• Compatible with current clinical strategies to control brain swelling
• Non-invasive treatment for brain injury
• Potentially more effective in lowering ICP in comparison to current treatments
• Can be administered via multiple routes
• Can be administered at different time points following TBI
• Potentially fewer side-effects compared to existing treatments

Lead Inventor:

Barclay Morrison III, Ph. D.

Patent Information:

Patent Status

Related Publications:

• Washington PM, Lee C, Dwyer MKR, Konofagou EE, Kernie SG, Morrison B 3rd. “Hyaluronidase reduced edema after experimental traumatic brain injury” J Cereb Blood Flow Metab. 2020 Oct; 40(10): 2026-2037.

Tech Ventures Reference:

• IR CU18154

• Licensing Contact: Kristin Neuman