cns injury

The role of the HGF/c-Met pathway has been extensively studied in central nervous system (CNS) injuries such as acute spinal cord injury and cerebral ischemia, or stroke. A similar HGF/c-Met timing mismatch to the one observed in acute kidney injury is also present in CNS injuries, and both we and independent researchers have demonstrated via in vivo studies that administration of ANG-3777 or exogenous HGF can reduce the severity of and enhance the recovery from acute injuries to the brain and spinal cord.1

CNS Injury Related to Stroke

Cerebral ischemia, or stroke, is a form of acute brain injury related to loss of blood flow to the brain from blocked blood vessels and causing irreversible degenerative damage to brain neurons. HGF is a potent pro-angiogenic (regeneration of blood vessels) drug and it also protects endothelial cells against cell death, which we believe may be particularly important since mature neurons cannot duplicate themselves. Additionally, the lack of oxygen caused by the stroke activates a fibrotic process resulting in scarring of neurons and brain tissue. HGF is reported to be capable of inhibiting or decreasing scar formation, which is critical for nerve regeneration and functional reconstruction.2 Acute delivery of HGF has also been shown to induce long-term neuroprotection with enhanced motor coordination recovery with the promotion of neuron survival continuing even after treatment discontinuation.3

While several drugs are approved to prevent strokes or subsequent strokes in certain populations, there is no FDA approved therapy for treating the damage caused by strokes.

Spinal Cord Injury

When studying animal models of acute spinal cord injury, researchers determined c-Met, the specific receptor for HGF, spikes sharply while the release of endogenous HGF is relatively modest. This mirrors the HGF/c-Met timing mismatch described in other acute organ injuries. Introducing HGF to the model via the use of an HGF-expressing viral vector significantly increased neuron and oligodendrocyte survival, angiogenesis and axonal regeneration, reduced total damage and promoted functional recovery in rats after spinal cord injury.4

REFERENCES

  1. Kitamura, et al. 2019, International Journal of Molecular Sciences
  2. Zeng, et al 2015, Experimental and Therapeutic Medicine
  3. Doeppner, et al 2011, Journal of Cerebral Blood Flow & Metabolism
  4. Kitimura, et al 2019