Probing Acetylcholinesterase Activity In Autism Using Novel Multimodal MRI Contrast Agents
After finishing his bachelor’s degree from RKMRC Narendrapur, India, Sajal went to IIT Kanpur to receive his master’s degree in Chemistry. In 2015, he started his PhD under the supervision of Dr. Jonathan L. Sessler at the University of Texas at Austin, USA. Sajal’s doctoral research encompasses developing anticancer metal complexes and evaluating their function as immunotherapeutic drugs. In his postdoc, Sajal will work on synthesizing small molecule contrast agents for mechanistic MRI-based studies of brain function in health and disease.
Autism spectrum disorders (ASD) are a diverse family of neurodevelopmental conditions that lack any consistent biomarkers to date. The enzyme acetylcholinesterase, which degrades acetylcholine at cholinergic synapses, has been emerging as potential therapeutic target in ASDs, and could serve as synapse-specific biomarker for these disorders. However, probe technologies to correlate AChE activity and ASD remained elusive. Our current work therefore seeks to design and validate novel AChE-sensitive MRI contrast agents to probe cholinergic phenotypes in ASD models, facilitate therapy development, and ultimately establish a non-invasive diagnostic tool for clinical evaluation of autistic patients. Our approach will use a previously validated molecular mechanism developed in the Jasanoff lab to image brain enzyme activity in animal models. Furthermore, these new contrast agents will be designed to facilitate probing AChE activity via multimodal imaging in addition to MRI. This added feature will permit valuable integration of readouts obtained over a range of spatial scales, both in living subjects and postmortem tissue. In concert, this project promises to yield an innovative and important tool for autism research, with the potential for future extension to evaluation of cholinergic function in human subjects.
Keywords: Biomarker for ASD, Acetylcholinesterase, MRI contrast agents, multimodal imaging