Dream duo could reverse stroke induced brain damage

Written by Adam Price-Evans

A team of researchers led by Berislav Zlokovic (University of California, CA, USA) has developed a novel therapeutic technique that holds promise for reversing stroke-induced long-term disability. The approach involves the utilization of a US FDA-approved protein to drive the formation of functional neurons.
Activated protein C (APC) is a blood protease involved with regulating anticoagulation and various cell signaling pathways. Formerly studied as a neuroprotectant in ischemic stroke patients, a recombinant variant of APC, termed 3K3A-APC, has been demonstrated to stimulate the production of neurons from human stem cells grafted into the stroke-damaged mouse brain.

The team transplanted human neural stem cells in mice one week post-ischemia, followed by the administration of 3K3A-APC or a placebo over a seven day period. It was demonstrated that 3K3A-APC treatment was associated with a 16-fold increase in human stem cell-derived neuron formation compared to the control group.

“Functional deficit after five weeks of stroke were minimized, and the mice were almost back to normal in terms of motor and sensorimotor functions,” stated Zlokovic. “Synapses formed between transplanted cells and host cells, so there is functional activation and cooperation of transplanted cells in the host circuitry.”

The motor and sensorimotor improvements observed were also lost upon the extermination of human stem cell-derived neurons, suggesting their importance for recovery from stroke-related disability.

Zlokovic’s team aim next to replicate the success of this animal study in a Phase II clinical trial with the hope that this combination therapy will also stimulate functional neuronal growth in humans. Based on the outcome of this trial, the team also plan to apply this neural stem cell graft and 3K3A-APC treatment to other neurological conditions.

Sources: Wang Y, Zhao Z, Rege SV et al. 3K3A–activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice. Nat Med. doi: 10.1038/nm.4154 (2016) (Epub ahead of print); http://news.usc.edu/104649/theres-hope-for-reversing-stroke-induced-long-term-disability/