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Nerve Damage Imaging and Single-Cell Tracking Gene Therapy are Highlights at World Molecular Imaging Society Annual Congress
Date:9/14/2019

Two studies presented at the annual Congress of the World Molecular imaging Society (WMIS) focused on non-invasive real-time tracking of gene therapy and advances to decrease nerve damage using Fluorescence image-guided surgery.

With mean survival rate of five years (and most cases fatal) lysomal storage diseases (LSD) are among the most dismal of prognosis in all of medicine. In the study Real-Time Tracking of Gene Therapy by Bioactivated MR Probes, Thomas Meade, Ph.D., Professor, Northwestern University, stated that LSDs represent a large number of monogenetic diseases and, while rare, the prevalence is to hemophilia. The transformative results documented in an adeno-associated virus (AAV) gene therapy clinical trial in infants, affected by spinal muscular atrophy, demonstrated unequivocally the potential of in vivo gene transfer to treat monogenic neurological disorders. To date there is a lack of non-invasive ways to determine biodistribution or activity levels of these AAV therapies in patients.

“We pioneered the development of bioresponsive (bio-activated) MR contrast agents and since then the library of this class of probes has expanded from enzyme activated agents to include pH sensitive and redox activated,” said Dr. Meade. “In our research, we want to determine if a new class of MR contrast agents could track the delivery of a gene by a noninvasive technique (MR imaging). The need for non-invasive, disease specific biomarkers that reflect treatment efficacy is paramount and not limited to gene therapy, but also applies to anything that augments the targeted enzyme activity.”

According to Dr. Meade, his team is developing a new class of bioresponsive MR probes to track enzymatic activity in any organ, peripheral nervous system (PNS), or central nervous system (CNS) over time. As a result, gene therapy can be noninvasively monitored at both where and when the gene of interest is activated.

“The number of academic and biotech led programs has risen exponentially in the last few years,” Dr. Meade concluded. “It is indeed an exciting and hopeful new era for the gene therapy field, but effective clinical trials with shortened paths to approval will require robust biomarkers to track therapeutic effect. It is our goal to support this important effort.”

In the Nerve-Sparing Agents for IGS (Image Guided Surgery) presentation, Connor Barth, Ph.D., Senior Research Associate, Oregon Health & Science University, speaks about the widespread issue of resulting nerve damage from surgery.

“Nerve damage plagues surgical outcomes, significantly affecting post-surgical quality of life,” said Dr. Barth. “Some 600,000 patients are affected by nerve damage during surgery annually in the United States. For some procedures, such as the radical prostatectomy, in which the prostate is removed as a prostate cancer cure, the rate of nerve damage can be as high as 60 percent.”

During surgery, intraoperative nerve detection is completed using anatomical knowledge and conventional white light visualization when possible. However, neuroanatomy is variable between patients, especially in injured and diseased states that would be present during surgery, and nerves are typically protected deep within the tissue so that white light visualization is largely impossible. Fluorescence image-guided surgery offers a potential means for enhanced intraoperative nerve identification and preservation. To date, a variety of nerve-specific fluorophores have been tested in preclinical models; however, a clinically approved nerve-specific contrast agent does not yet exist.

“We have developed nerve-specific fluorophores that provide direct and buried nerve visualization during surgery with near-infrared fluorescence,” Dr. Barth stated.

“The purpose of this study was to generate clinically relevant formulations and quantify the toxicity and pharmacology of our first-in-class, near-infrared nerve specific fluorophores. This work takes our technology one step closer to clinical translation for use during fluorescence-guided surgery.”

Dr. Barth believes this work will ultimately have a broad impact on surgical outcomes, significantly improving the rates of nerve damage during surgery and thus higher post-surgical quality of life for patients. This technology could also serve to make procedures available to surgeons where potential nerve damage has been prohibitive, broadening the clinical impact by enabling curative surgical treatments.

ABOUT WORLD MOLECULAR IMAGING SOCIETY

The WMIS is dedicated to developing and promoting translational research through multimodality molecular imaging. The education and abstract-driven WMIC is the annual meeting of the WMIS and provides a unique setting for scientists and clinicians with very diverse backgrounds to interact, present, and follow cutting-edge advances in the rapidly expanding field of molecular imaging that impacts nearly every biomedical discipline. Industry exhibits at the congress included corporations who have created the latest advances in preclinical and clinical imaging approaches and equipment, providing a complete molecular imaging educational technology showcase. For more information: http://www.wmis.org

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