How far has humanity come in preventing -- or rewinding -- neurodegeneration? Designed Cells, a Korean stem cell therapy company, has the ambitious dream of achieving something no one has ever yet succeeded in doing: curing dementia.

Dementia, which can be but is not always a symptom of Alzheimer’s disease, is a cognitive dysfunction commonly found in aged seniors. However, it is not a normal part of aging -- the destructive effects of dementia go beyond the ordinary forgetfulness that might be expected as a person ages, according to the World Health Organization.

Normal age-associated memory impairment exists, but is not severe enough to disrupt a person’s daily life as dementia does. With age, people naturally experience difficulty remembering things, to some degree. But they can still learn and remember new things, and can carry on normally with life.

What causes dementia, per the scientific consensus to date, is an abnormal accumulation of unhealthy proteins in the brain -- phophorylated tau proteins and amyloid beta plaques. These proteins block the communication paths of neural cells, leading to their death and to diminished vivacity in cerebral activity.

While research is still underway to find various routes to tackle neurodegeneration, scientists and drugmakers for now are focusing on therapeutic agents that might possibly inhibit the aggregation (phosphorylation) of tau proteins and scatter the deposition of amyloid beta peptides. None have been successful so far.

Global companies Lilly, Boehringer-Ingelheim, Pfizer, Roche and Biogen have dabbled in the use of anti-amyloid beta antibodies to remove the causative proteins. Lilly-Astrazeneca and MSD have tried using beta-secretase inhibitors to block the additional production of amyloid beta peptides. All were very expensive, time-consuming projects that were eventually tossed in late-stage clinical developments after proving futile.

But what about stem cells?

Professor Kim Yun-bae, CEO of Designed Cells, is confident that his company will be the game changer in the fight against dementia.

Designed Cells differs from other stem cell companies in that it crafts optimal stem cells to delegate the task of reinvigorating and replenishing neural cells, according to the company.

Stem cells are pluripotent. Rival companies studying the use of mesenchymal stem cells to treat transgenic mice born with a mouse model of Alzheimer’s disease showed that they had meaningful effects on cognitive function, with results suggesting up to 50 percent amelioration of dementia. But when the treatment was given to humans, whose brains are hundreds of times bigger, the drugs showed less efficacy than what was hoped for.

To regrow neural cells, the best candidate for the job to overcome brain diseases is neural stem cells, Kim said.

Not only does Designed Cells use NSCs, the cells overexpress cognitive function genes to boost recovery of learning and memory, he explained.

"We found that acetylcholine (ACh) depletion was responsible for cognitive deficits, and we transfected ChAT gene, producing ACh responsible for memory acquisition, to NSCs," Kim said.

The result was an astounding full recovery in cognitive function, Kim said, adding, "The mice that were given our treatment became super mice -- they performed better in memory tests than their control group."



Designed Cells explains that its investigative treatment showed effectiveness in improving cognitive function in transgenic mice as well as in animals with all kinds of memory impairment due to hippocampal injury, cholinergic neuron degeneration, amygdala injury, stroke and even super-aging -- by increasing brain ACh levels.

Kim said Designed Cells’ medication can be applied to any disease if the stem cells are encoded with corresponding (target) functional genes.

For mild cases of degeneration, Designed Cells has another technology using “exosomes” to slow the progress of the disease and protect the brain.

Exosomes are nanoparticles containing functional molecules that contain hundreds to thousands of proteins including growth factors, micro-RNAs and lipids.

"We have the technology to collect a large amount of exosomes by cultivating stem cells under a hypoxic condition following cytokine-stimulation," Kim said.

"The exosomes enter the brain by readily penetrating blood-brain barrier after intravenous injection or nasal mucosa following intranasal dropping, and regenerate neurons in animals with brain diseases such as Alzheimer’s disease," he said.

These exosomes can be applied to restore cells and tissues in glaucoma, osteoarthritis, skin aging, and diverse defective and inflammatory injuries, according to Designed Cells.

These are all ailments associated with old age. In a world where the scales of the human population are tilting more toward aged rather than youthful, these are all pressing health care issues.

According to WHO, there are roughly 50 million people suffering from dementia, whose care and management costs some 971 trillion won ($832.5 billion) annually. By 2050, the number of dementia patients is forecast to triple to 150 million.

Founded in 2016, Designed Cells is getting ready to enter phase 1 human clinical trials of its ChAT gene-encoding NSC treatment for dementia by early 2022. The company has 30 patents for the functional gene-encoding stem cells, including dementia-therapeutic stem cells, registered in six advanced countries.

By Lim Jeong-yeo (kaylalim@heraldcorp.com)