NU 2010-125

Inventor

Shu Q. Liu

Short Description

A biologic for neuroprotection during the acute phase of a stroke

Background

Stroke is the leading cause of serious, long-term disability in the United States. As adult neurons possess a limited capacity for protection and regeneration, infarcted brain tissue is often replaced with fibrotic tissues, resulting in permanent impairment of nervous functions. One desired therapeutic approach is to protect the brain from ischemic injury during the acute phase of a stroke, minimizing the loss of neurons. However, few effective therapies have been established for such a purpose in prior research.

Abstract

A Northwestern scientist has discovered a surprising connection between neuroprotection and liver cells. The researcher found that in response to an experimental stroke in mice, hepatocytes upregulate specific genes encoding secreted proteins, including FGF21, RELM and TFF3.. When mice with acute cerebral ischemia were administered with recombinant FGF21, RELM and TFF3, a significant reduction (p<0.01, p<0.01 and p<0.02, respectively) in cerebral infarction was observed.  Further, these mice showed significant improvement in the gripping strength of the impaired forelimb. These initial in vivo results suggest that these particular secretory factors could be potential biologic therapeutics to help alleviate brain injury in stroke patients. These preliminary results support further investigations in clinical trials.

Applications

• Neuroprotective therapeutic drug treatment for human stroke patients

Advantages

• Ease of intravenous administration
• Capability of crossing the blood-brain barrier
• Initial promising in vivo results

Publications

Liu SQ, Roberts D, Zhang B, Ren Y, Zhang LQ, et al. (2013) Trefoil Factor 3 as an Endocrine Neuroprotective Factor from the Liver in Experimental Cerebral Ischemia/Reperfusion Injury. PLOS ONE 8(10): e77732.

IP Status

Issued US patent Nos. 8,754,044 and 9,114,116

Graph showing the neuroprotective effect of secreted factors FGF21, RELM-gamma and TFF3.