Photograph by Frank Mueller

Dr. Nicola Brasch, assistant professor of chemistry, leads Kent State’s Bioinorganic and Medicinal Chemistry Research Group. She is working with colleagues from The Cleveland Clinic to explore a new, patented compound derived from vitamin B12.

A STORY OF SYNTHESIS AND STUDENT SUCCESS
Doctoral student Edward Suarez-Moreira is a co-inventor of the procedure to synthesize NAC-B12. Read about his work that has been gaining national attention.

PODCAST: ANATOMY OF TECHNOLOGY TRANSFER
Gregory Wilson, associate vice president for economic development, gives an in-depth report on the world of university research and the road from idea to reality.

Vitamin Power

New B-12 compound may defend against ailments of aging

Anyone who’s made fruit salad knows how the white flesh of an otherwise picture-perfect apple will turn brown once it’s removed from the protection of its glossy red skin.

Dr. Nicola Brasch, assistant professor of chemistry, likens the reaction — known as oxidative stress — to the human body’s aging process. Furthermore, the buildup of this molecular and cellular damage increases our vulnerabilities to illness as we grow older.

Oxidative stress is associated with the production of reactive, harmful, oxygen-containing radicals, which attack and damage important molecules in our bodies, including proteins, lipids and DNA, Brasch says. Oxidative stress also plays a role in a wide variety of diseases — most of them linked to aging — including heart disease, cancer, diabetes and various neurological disorders, such as Alzheimer’s disease and other dementias.

Brasch, who leads Kent State’s Bioinorganic and Medicinal Chemistry Research Group, is working with colleagues from The Cleveland Clinic Lerner Research Institute to explore the possibility that a new, patented compound derived from vitamin B₁₂ might curb this process and consequently reduce the incidence of many diseases that plague humanity.

Take your vitamins

Vitamin B₁₂ is very busy in our bodies. It plays a role in metabolizing homocysteine, an amino acid in the blood. A deficiency of B₁₂, according to recent research findings, can lead to increased risk of heart disease, stroke and cognitive impairment. Pernicious anemia and neurological disorders top the list of B₁₂ deficiency-related health consequences.

B₁₂ is synthesized by a variety of microorganisms found in soil, water and the stomachs and intestines of animals. Vegetarians and individuals who don’t eat much meat are more likely to suffer from B₁₂ deficiency; after all, humans obtain their dally requirement of vitamin B₁₂ almost exclusively from meat products.

Despite the abundance and variety of food in the Western world, vitamin deficiencies remain widespread. Approximately 20 percent or more of the U.S. population over the age of 65 are believed to be B₁₂ deficient; the deficiency happens during the course of a lifetime, usually without one’s knowledge, and the effects manifest later in life. The body’s natural aging process exacerbates the problem — as people age, levels of a protein that assists in absorption of B₁₂ decrease.

Compound potential

In the 1990s a Welsh physician, Dr. Andrew McCaddon, noted a correlation between patients from the same family who had low levels of vitamin B₁₂ and also developed Alzheimer’s disease. His research spawned interest in potential B₁₂-related interventions in the fight against diseases associated with aging.

McCaddon found patients with impaired cognitive function responded better to treatment with a vitamin B₁₂/thiol formulation (B₁₂/N-acetylcysteine, or NAC) than to treatment with vitamin B12 alone. He patented the use of thiol compounds of B₁₂.

Based on McCaddon’s discovery, Brasch postulated that a new compound might be formed as a result of a reaction between NAC and B₁₂, and that this compound, rather than the NAC and B₁₂ individually, might be responsible for the therapeutic effects McCaddon observed. A graduate student in her lab, Edward Suarez-Moreira, thus developed a method to synthesize a novel compound — N-acetylcysteinylcobalamin, or NAC-B₁₂.

NAC- B₁₂ currently is being tested for its ability to protect against oxidative stress in the laboratory of research collaborator Dr. John Williams, at the Centre for Stress Research, University College Chester, United Kingdom.

Early results of the testing show promise. First, cells are exposed to a solution containing the new compound; then they are “washed” and exposed to another chemical that causes oxidative stress. Experiments confirm that NAC- B₁₂ provides superior protection from oxidative stress compared to other forms of vitamin B₁₂. Next, researchers will investigate the mechanisms causing the increased cell protection.

License to heal

Pamlab, L.L.C., a Louisiana-based pharmaceutical company, has licensed from Kent State University, through the university’s Office of Technology Transfer, both the synthesis of NAC-B₁₂ and its therapeutic applications for the treatment of diseases associated with oxidative stress. “We are extremely pleased to see this promising compound and the work of Dr. Brasch progressing toward commercialization with Pamlab” notes Gregory Wilson, associate vice president for economic development and strategic partnerships.

“The first step will be to investigate the therapeutic potential of NAC-B₁₂ in a range of cell types, including brain cells,” Brasch says. “If any of these results look promising, the next step is to evaluate the pharmacological properties of NAC-B₁₂.”

While Brasch says the chances of a new compound making it onto pharmacy shelves anytime soon are very low, she points out that the majority of pharmaceuticals we use wouldn’t exist without the exchange of knowledge and technology between universities and private companies.

Investment in scientific research can be an expensive gamble. As we seek drugs to alleviate pain and cure diseases, the stakes are high — but so are the rewards. For more information, visit Dr. Nicola Brasch's Department of Chemistry Web page.