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WSUPG neurologists secure discovery grant for imaging biomarker in Huntington’s Disease


01.07.2016

Wayne State University Physician Group neurologists Omar Khan, M.D., and Navid Seraji-Bozorgzad, M.D., will serve as joint co-principal investigators for a series of grants under an early phase discovery agreement between Wayne State University and Cambridge, Mass.-based Biogen Idec. to discover an imaging biomarker in Huntington’s disease.

The grant includes $344,000 for the first year of research and $344,000 for the second year.

Dr. Khan is a professor and chair of Neurology and director of the Sastry Foundation Advanced Imaging Laboratory at the WSU School of Medicine. Dr. Seraji-Bozorgzad is an assistant professor of Neurology and associate director of the Sastry lab.

Huntington’s disease, an inherited progressive and fatal neurodegenerative genetic disorder, has no cure; patients rely only on symptomatic treatment. Thus, there is an urgent need to identify biomarkers that are able to monitor disease progression and assess the development and efficacy of novel disease-modifying drugs, Dr. Khan said.

The disease manifests with chorea, cognitive and psychiatric symptoms. There are an estimated 30,000 symptomatic patients in the United States, with another 200,000 at risk of inheriting the disease.

Advancements in genetics allow for carrier identification, but much is still unknown about the mechanisms underlying the development of overt clinical symptoms and the transitional period between pre-manifestation and manifestation of the disease.

The WSU study will enroll patients beginning this month with either pre-manifestation Huntington’s disease or very early symptoms of the disease.

“This will allow us to develop a reliable imaging biomarker in Huntington’s disease and expedite therapeutic development,” Dr. Khan said. “To date, there is no cure or disease-modifying therapy available for Huntington’s disease. But several gene-based therapies using an ‘anti-sense’ approach are in rapid phase development and in active discussions with us. Thus, this appears to be promising at so many levels, but most importantly for patients and their families.”

Huntington’s disease prevalence varies by ethnic origin and different genetic profiles, with six cases per 100,000 in Caucasianpopulations of North America and Western Europe, versus 0.5 cases per 100,000 in those of Asian descent. The disease usually appears in the mid-40s, although juvenile onset and late onset are not uncommon. Subclinical changes and pathological processes are thought to precede the initiation of symptoms by several years.

While neuroimaging techniques such as magnetic resonance imaging and positron emission tomography have provided important advances in disease understanding, and high-resolution optical coherence tomography has created novel opportunities to investigate neurodegenerative disorders, no single technique to date has been validated as an optimal biomarker in Huntington’s disease.

“This is truly a novel in vivo imaging approach that incorporates (high field strength 3-tesla) brain MRI scanning using state-of-the-art imaging sequences and post-processing. Following brain MRI scans, patients will undergo Positron Emission Tomography scanning using the PK1115 ligand targeting microglial activation in the brain. In between the two imaging scans, all patients will undergo 3D optical coherence tomography of the retina, where our preliminary data show unique retinal signatures not seen in age-matched controls,” Dr. Khan said.

The three-pronged imaging approach has never been studied in Huntington’s disease. Imaging will be repeated after six months to examine changes.

“This unique approach will allow us to detect tissue injury at the molecular level as well as identify potential microglial activation as an inflammatory molecular biomarker in an otherwise classic neurodegenerative disease,” Dr. Seraji- Bozorgzad added.

The unique MRI brain scans will allow comprehensive tissue mapping and detection of the earliest tissue injury with unique patterns to Huntington’s disease, such as frontal lobe damage, not detected with conventional brain MRIs.

“This is the only study in the entire field that combines PET and MRI in Huntington’s disease, in addition to retinal imaging with OCT,” Dr. Khan said.

The PET-MRI co-registration software was developed by PET Center experts, led by co-investigator Csaba Juhasz, M.D., a WSU professor of Pediatrics and of Neurology.

“Without the help of the colleagues in the PET Center and their internationally recognized expertise, this kind of state-of-the-art work would be not be possible. This is also one of the main reasons we were successful in securing this multi-sequential grant,” Dr. Khan added.

The work was presented at a meeting of the American Neurological Association in 2015.

“Wayne State University is the only site in the world to embark upon a highly novel imaging and critically-needed study, which speaks volumes of the pioneering research being conducted here,” Dr. Khan said.

The Neurogenetics Clinic in the Department of Neurology, located within the University Health Center, was established by the late James Garbern, M.D., Ph.D., in 2004. “Without his tireless work and commitment, this work today would not be possible,” Dr. Khan said. “We have one of the largest Huntington’s disease clinics in the United States, which grew thanks to the dedication of Dr. Garbern.”

The researchers plan to work closely with the Michigan Chapter of the Huntington’s Disease Society of America during the study



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