Neuromuscular Diseases and ALS

The neuromuscular research program is focused on the very common problem of diabetic neuropathy and the rare but uniformly fatal disease, amyotrophic lateral sclerosis (ALS). In the laboratory, we harness the advantages of cellular disease models, animal disease models, stem cell biology and computer-based analyses to gain comprehensive insight into disease processes.  In the clinic, we translate our findings into clinical studies and therapeutic trials and augment these approaches with advanced neuroimaging.

For diabetic neuropathy UM investigators have NIH funding for a collaborative project identifying genetic transcripts, proteins, and metabolites that are altered in both diabetic patients and rodent models to identify common mechanisms and molecular responses in complication-prone tissues. As part of an additional multi-investigator NIH-funded project we are examining energetic pathways involved in the onset of complications in nerve, kidney, and eye to define the specific changes in cellular substrate metabolism that drive the development of diabetic complications. Finally, we are utilizing novel neuroimaging techniques to uncover alterations in excitation-inhibition balance in the brains of individuals with diabetic neuropathy.

In ALS, we have established the University of Michigan ALS Patient Repository (UMAPR) for blood, skin, fibroblasts, lymphocytes, genomic DNA, clinical data, lifestyle exposure information, and postmortem tissue for ALS patients and control individuals, that are being utilized in a CDC/ATSDR-funded study to identify potential ALS risk factors associated with environmental exposures and to characterize how epigenetic modifications impact gene expression and contribute to the development of ALS. We also examining the therapeutic potential of newly developed stem cell lines in the treatment of ALS and examining the efficacy of intracranial cellular transplantation in an animal model of Alzheimer’s disease, as a demonstration of the translational potential of our ALS cellular therapy strategies to other neurological disorders. Finally, we are developing advanced neuroimaging approaches as a potential diagnostic and prognostic tool to understand and assess ALS in human subjects.

Clinical translational trials include observational studies involving patients from the UM metabolic disease clinics and bariatric surgery programs, collaborative studies with groups from India and China to determine if the metabolic drivers of diabetic neuropathy are different in these diverse populations, health services research studies to evaluate the current clinical practice related to the diagnostic evaluation of diabetic neuropathy, and an investigator-initiated phase 2 clinical trial of stem cell therapy to treat ALS.