Facts & Milestones
With over $1 billion in total research spending, the University of Michigan is the #1 public university in research spending according to the National Science Foundation. And of that dollar amount, over $440 million is in medical research. Here are a few more statistics illustrating the robust nature of the UMMS research enterprise:

• #6 Medical Research School in the United States, U.S. News & World Report
• 118 invention reports and 36 license agreements in 2010
• Three hospitals and over 40 Health Centers
• 1.7 million patients served each year, with 350,000+ in active clinical studies
• 1.6+ million square feet of laboratory space
• 34 Institute of Medicine members
• 23 Howard Hughes Medical Institute Fellows

Pioneers in research and clinical treatment, our faculty and staff have been at the cutting edge of biomedical research since the U-M Medical School was founded in 1848.

Story credit: Ann Curtis, UMMS Business Development

One Path To Discovery and Commercialization
Researchers at the University of Michigan Comprehensive Cancer Center have developed a new drug called AT-406 with potential to treat multiple types of cancer.

A study, published in the Journal of Medicinal Chemistry, showed that AT-406 effectively targets proteins that block normal cell death from occurring. Blocking these proteins caused tumor cells to die, while not harming normal cells. The researchers believe the drug could potentially be used alone or in combination with other treatments.

The normal cell death process, called apoptosis, is what keeps normal cells in check. When apoptosis is disrupted, cells reproduce uncontrollably, which is a hallmark of human cancer.

“Removing key apoptosis blockades in tumor cells is a completely new cancer therapeutic approach and could have benefit for the treatment of many types of human tumors,” says study author Shaomeng Wang, Ph.D., Warner-Lambert/Parke-Davis Professor in Medicine and director of the Cancer Drug Discovery Program at the U-M Comprehensive Cancer Center.

Wang’s laboratory has been pursuing new cancer treatments aimed at this cell death pathway since 2003. His team designed and made AT-406 and tested it in the laboratory in 2006. The small-molecule drug hones in directly on the proteins-called inhibitor of apoptosis proteins or IAPs-that block cell death. The researchers found that AT-406 destroyed these proteins in cancer cells. Meanwhile, the drug had little to no effect on normal cells.

In animal models, the drug shrank tumors but caused few side effects. The drug is designed to be taken by mouth, which researchers say will make it easier than traditional intravenous chemotherapies to administer.

Patent applications covering the drug are exclusively licensed to Ascenta Therapeutics, a privately-held, clinical stage biopharmaceutical company co-founded by Wang. After extensive testing, Ascenta began the first clinical trial in 2010 testing AT-406 for cancer treatment. This trial, which is being tested in all solid tumors, is offered at the U-M Comprehensive Cancer Center, Duke University and the Mayo Clinic. Ascenta has also recently opened a second trial of AT-406 in high-risk acute myeloid leukemia at the U-M Comprehensive Cancer Center. Several more clinical trials are planned.

“Our research goal and our passion is to translate our science and discovery into new and effective medicines for patients,” Wang says. “I am delighted to see the drug we have designed, made and tested in our laboratory now being given to patients right here in the same building.”

Story credit: Nicole Fawcett, UMHS PRMC

Blocking Neurodegeneration In Adult Form of Fragile X
Expression of a toxic RNA that leads to Fragile X Tremor Ataxia Syndrome is modifiable by genetic or pharmacologic means, according to new research from U-M Medical School scientists.

In the study published in the journal Public Library Of Science Genetics, U-M's Peter K. Todd, M.D., Ph.D., led a team of researchers who examined the expression of a toxic messenger RNA (mRNA) seen in the brains of those afflicted with the syndrome.

Fragile X Tremor Ataxia Syndrome (FXTAS) is usually found in older adults, who often have grandchildren afflicted with Fragile X. Those affected with the adult form of the syndrome have slow gait, tremors, dementia and balance problems.  The symptoms are caused by overproduction of a toxic mRNA in the brain that causes neurodegeneration. 

"We found that the expression of this toxic mRNA is dynamic and modifiable," says Todd, who is an assistant professor in U-M's Department of Neurology. "There is a potential for modifying the increased production of the toxic RNA with drugs that inhibit histone acetylation."

FXTAS is an under-diagnosed syndrome that was only discovered about 10 years ago, when researchers discovered the grandfathers of children with Fragile X were displaying common symptoms. It is one of three known Fragile X disorders that result from changes in the Fragile X gene. The altered gene can be passed down through generations, affecting both genders at different stages in life.

About 1 in 3,000 men and about 1 in 5,200 women in the general population will develop symptoms of FXTAS, according to the National Fragile X Foundation. Current estimates suggest that about 30-40 percent of male Fragile X gene carriers over 50 years of age, within families already known to have someone with a Fragile X-associated disorder, will ultimately exhibit some features of FXTAS.

Fragile X is the most common cause of developmental delay in boys and is the most common known single gene cause of autism.

Using both fruit fly models and human cells, the U-M researchers found that drugs that inhibit histone acetyltransferases modify the brain changes associated with FXTAS and could provide the pathway to a therapeutic target.

"These drugs that we used are too toxic for use in patients but the important finding is that we have a better idea of what's driving this syndrome and proof of principle that those brain changes can be modified," says Todd.

"Our findings underscore the need for developing more specific modifiers of expression at the Fragile X gene, with the long-term goal of developing preventive therapy for FXTAS patients," says Todd.

Todd stressed the need for more research into neurodegenerative diseases like FXTAS, which can be devastating to families. "This should be a high priority. Neurodegeneration robs people of their humanity," Todd says. "To lead a happy and fruitful life, you have to protect the brain."

Story credit: Mary Masson, UMHS PRMC