N.C. A&T Bioengineering Researcher Aims to Develop Mini-brain in Fight against Alzheimer’s Disease

EAST GREENSBORO, N.C. (March 2, 2021) – Yeoheung Yun, Ph.D., a bioengineering professor at North Carolina Agricultural and Technical State University, was awarded $1.43 million from the National Institutes of Health (NIH) to develop a functional mini-brain model in the fight against Alzheimer’s disease (AD). According to the Alzheimer’s Association, AD affects more than 6 million Americans and is the most common cause of dementia.

Yun’s highly qualified team, comprised of two clinician experts in brain disease and immunology, and a scientist in iPSC-derived cell (Induced Pluripotent Stem Cells) technology, will create a mini-brain model by designing a “tissue construct platform” to replicate three key areas of entry for Alzheimer’s-combating drugs. The funding for this novel work comes from NIH’s National Institute of Neurological Disorders and Stroke.

Yun has an extensive background in mechanical engineering and mechatronics engineering from South Korea. With these degrees, he developed retinal imaging equipment for two years before moving to Cincinnati to pursue his Ph.D.

“Bioengineering itself has a short history; it is still emerging and evolves every day,” said Yun. “Learning new things is fun for me. Blending the engineering and medical disciplines creates fascinating and challenging problems.”

Yun became the first faculty member of A&T’s bioengineering program when it was established in 2010. Within five years, he was working on a Department of Defense grant screening nerve agents, such as sarin gas, to study their toxic effects on mini-brain platforms. It was this work that laid the foundation for the tissue construct platform Yun will use to answer questions critical to combatting Alzheimer’s.

Yun will collaborate with colleagues at multiple universities including Florida State University, Duke University, the University of North Carolina at Chapel Hill and Wake Forest University for this research. Stem cells derived from AD patients will be used to recreate the cortex of the brain tissue since this area plays a significant role in memory.

“A human brain, or something equivalent to it, must be used for this drug delivery research because animal models do not fully recapitulate the spectrum of human neuropathology,” said Yun. “Because the differences between the human and animal brain are significant, the only way to change the game on Alzheimer’s research is to ethically target treatment strategies focused on the human brain and human brain tissue equivalents.” 

Yun identifies three barriers for AD drugs to reach their targeted area. The proposed mini-brain tissue model will replicate these functions. Yun and his research collaborators must test if the drug treatments will be able to cross the blood-brain barrier that protects the brain, then determine if the immune system present within the brain perceives the presence of the medication as a foreign material. If the latter is the case, a cascade of reactions will begin whereby the brain will seek to protect itself from potentially helpful medication. Finally, if the drug passes these targets, Yun’s research team will evaluate if the drug treatment successfully reaches the target neurons required for the AD treatment to be effective.

Because of the number of uncertainties associated with the planned AD work, Yun and his team needed an effective test system alternative to the human brain for this research. Yun’s mini-brain tissue construct will be able to provide realistic and clinically relevant data and offer a viable platform for drug screening and personalized medicine.

Using the mini-brain platform, Yun and his research team seek to demonstrate if the drugs can effectively reach their targets and:

• Reduce and potentially crumble the build-up of beta amyloid plaques within the mini brain. Beta Amyloid is a protein derived from the amyloid precursor protein (APP) found within the cell membrane. As beta amyloid clumps together, plaques are formed, thus, inhibiting neurons from communicating with each other and causing inflammation; and
• Reduce the degree in which Tau neurofibrillary tangles form since the presence of these tangles prevent the neuron from receiving needed nutrients to be healthy. Thus, harming neuronal communication and eventually leading to neuronal death.

If the team’s AD treatment strategy is effective, their research will unlock more personalized medicine options for researchers and physicians seeking to treat Alzheimer’s disease and accelerate drug discovery and screening.

Yun is the principal investigator on this four-year NIH SCORE grant, which is equivalent in funding level to NIH’s R01 grant mechanism. He is also the graduate program director for A&T’s bioengineering program, director for the FIT BEST Laboratory (Fostering Innovation Through Biosystems for Enhanced Scientific Technologies) and previously served as a co-PI for the university’s the National Science Foundation Engineering Research Center for Revolutionizing Metallic Biomaterials.

Editor’s Note: Special thanks to the North Carolina A&T State University Center for Outreach in Alzheimer’s Aging and Community Health for providing feedback on the ways Alzheimer’s attacks the human brain.