University of Michigan researcher Peter Todd, MD, PhD, charts new waters to selectively turn the fragile X gene back on in human cells

turning on the Fragile X gene - Dr. Haenfler and Dr. Todd

Fragile X gene researcher, Peter Todd, MD, PhD

Swimming Upstream

Fish like salmon are born in fresh water streams and rivers.

When the time comes for them to breed, they return to the stream of their birth to lay eggs in the same spot where they were born. To accomplish this, they must swim upstream against the current or flow of the stream.

Taking a page out of the salmon DNA playbook, University of Michigan scientists Peter Todd, MD, PhD, and postdoctoral fellow Jill Haenfler, Ph.D., are exploring unchartered waters to find a cure for Fragile X Syndrome. The researchers are adapting CRISPR research to reactivate the FMR1 gene, which provides instructions for making a protein called FMRP — needed for normal brain development. CRISPR, pronounced “crisper”, is a new and innovative technique to cut and paste DNA in human cells.

“Previous Fragile X research has focused on the consequences of a loss of FMRP” said Todd, an assistant professor in the Department of Neurology in the University of Michigan Medical School. “We are trying to intervene at the first event which leads to Fragile X Syndrome, which is the turning off of the fragile X gene. If we can selectively turn this gene back on and make more FMRP in Fragile X patients, then we would have a really promising new treatment strategy.”

For their efforts, FRAXA is awarding the researchers $90,000 in a post doctoral fellowship grant over two years to reactivate FMR1 in Fragile X Syndrome stem cells. New developments in patient derived stem cells at UM’s MStem Cell Laboratories are at the core of their research.

“If we can show this works in patient cells, then it will suggest our methodology is sound and that such a strategy could be viable in patients if we can get the delivery right” said Todd, the grant’s lead investigator. “If we get the gene to work the way it is supposed to work, it will bypass a whole set of problems that occur when you try to fix the downstream consequences of losing FMRP.”

Todd said their research goal is to create new knowledge and approaches. If all goes well, the research will transition into more complicated systems within the next two years.

”Our best possible solution is to make more FMRP in Fragile X patients by selectively figuring out how to turn the gene back on,” Todd said. “We will be going as far upstream as possible.”

Also like salmon, this new line of research is really a return by Dr. Todd to his scientific “birth place”. After earning his BS in 1994 from the University of California, San Diego, he moved to the University of Wisconsin where he pursued a combined doctoral and medical degree (which he received in 2004). His PhD research focused on the synaptic defects that develop in Fragile X Syndrome, and his first ever research grant (given to his mentors Ken Mack, MD, PhD, and Jim Malter, MD) was an award from FRAXA that helped support his thesis work. “That grant made a big impact on my career and really helped launch my interest in working on Fragile X-associated disorders. I don’t know if I would still be in the Fragile X field today without that early support.”

After completing neurology residency, Dr. Todd came to the University of Michigan, where he joined the U-M faculty in 2010 as an assistant professor in Neurology. His other research is focused on Fragile X–associated tremor/ataxia syndrome (FXTAS), an “adult onset” neurodegenerative disorder typically affecting males who have a shorter repeat in their fragile X gene. His studies on FXTAS led him back to Fragile X Syndrome and trying to think of new approaches to this currently untreatable disease. As a neurologist, he sees adult patients with both Fragile X Syndrome and FXTAS at the University of Michigan Fragile X Clinic, which he co-directs.

Dr. Todd describes his research work as “very challenging,” yet “fascinating.”

“I love what I do,” he said. “I picked a research area that is hard but important because it gives me the opportunity to do something that is transformative and make a real difference in the lives of others. It’s exhilarating.”

Just like swimming up stream.

University of Michigan Fragile X Clinic

University of Michigan MStem Cell Lab

Todd Lab website

FRAXA was able to fund this project thanks to a generous gift from Franziska Klebe and her husband Chuck Samuelson, and John and Barbara Samuelson, through the John and Barbara Samuelson Foundation.

 


About the Author
Ted Coutilish author of Yale Professor Paul Lombroso studies STEP inhibitors for Fragile X
Ted Coutilish and his son, Andrew

Theodore G. Coutilish is celebrating his 10th year as Associate Vice President of Marketing at Eastern Michigan University, Ypsilanti, Michigan. Coutilish has enjoyed more than two decades of higher education marketing communications leadership experience. Since 2011, he has successfully led the university’s TRUEMU marketing campaign, leading to record new student enrollment.

Over the years, his peers have recognized his work with numerous prestigious awards, including IABC Detroit’s 2012 Communicator of the Year, the chapter’s highest honor, recognizing lifelong professional communications excellence. In addition, he and his wife, Mary Beth Langan, were recognized with the 2012 Halstead-Bresnahan Family Award at the 13th Annual International Fragile X Conference, Miami, Florida, recognizing those who make a profound difference to families affected by fragile X syndrome. Coutilish was named “Distinguished Alumni in 2013” by Grosse Pointe North High School, the school’s highest honor, recognizing professional and community achievements. He lives in the City of Grosse Pointe, Michigan, with his wife, and their son, Andrew, who has Autism and Fragile X Syndrome. He earned a MA in liberal studies with a concentration in communications from University of Detroit Mercy in 1994 and a BA in print journalism in 1987 from Wayne State University.


FRAXA Fellowship awarded May 2016

Targeted transcriptional reactivation of FMR1 in Fragile X Syndrome stem cells

Peter Todd MD, PhD
Principal Investigator

Jill Haenfler PhD
Postdoctoral Fellow

University of Michigan Medical Center

$45,000 in 2016
renewed for $45,000 in 2017