Dr. Ikezu’s quest for better memory

(EDITOR’S NOTE: The following story originally appeared in the Fall 2009 edition of UNMC Discover.

By the time he was 18, Tsuneya Ikezu, M.D., Ph.D., had studied Albert Einstein’s theories of relativity for six years.

“I asked many adults, but at age 12, I didn’t have the math skills to figure it out.”

Undeterred, he asked his parents for a book on the subject and began to study.

Now a scientist at UNMC, Dr. Ikezu applies the same persistence to another complex problem: inhibiting the progression of neurodegenerative disorders.

Earlier this year, Dr. Ikezu — professor of pharmacology and experimental neuroscience and director of the UNMC Center of Neurodegenerative Disorders — discovered a naturally-occurring, overactive enzyme that plays a role in the onset of dementia. The discovery led to $2 million in funding from a venture capital firm in Australia.

The money supports Dr. Ikezu’s work to find a compound to block the enzyme and prevent damage. His lab has developed a transgenic mouse model that demonstrates how the enzyme — known as tau-tubulin kinase1 (TTBK1) — induces memory impairment.

TTBK1 regulates the efficiency of neuronal communication. The mouse model study, published last year in the Journal of Neuroscience, revealed that TTBK1 is a potential therapeutic target for such neurodegenerative disorders as Alzheimer’s and Parkinson’s diseases.

“TTBK1 is a naturally-occurring enzyme in mice but in very low amounts,” he said. “When elevated it has the same effect on mice as it does in humans — memory impairment.”

Tsuneya Ikezu, M.D., Ph.D.

To test his theory, mice were placed in a circular water maze tank with six water paths and one submerged platform. The mice used spatial cues to locate the platform after several trials.

Once the mice learned where the submerged platform was, it was moved so the mice would have to relearn its location. At first, the mice were always able to find the platform again, but as their memory worsened with age, they forgot where the platform was.

With hypothesis confirmed, Dr. Ikezu now searches for a drug to inhibit the overactivity of TTBK1. He hopes to find options among the 7,000 proprietary drug compounds he purchased with grant money from the Australian firm.

“Once we find the compound that regulates TTBK1, we’ll test it on human brain specimens,” he said. “Then, we will begin to develop a pharmaceutical quality drug to use in clinical trials.”