Research Career Scientist for Naren Banik, PhD

Current research activities are focused on Spinal Cord Injury (SCI), Parkinson’s Disease (PD), and Multiple
Sclerosis (MS). SCI is a complex debilitating condition leading to life-long neurological deficits as well as bone
loss and muscle atrophy due to immobility. Our laboratory was among the first to show that estrogen (E2) drives
neuroprotection in experimental SCI in rats, suggesting E2 warrants clinical evaluation in neurotrauma. New
smart drug delivery techniques, including nanoparticles, may allow for increased drug safety and improved
efficacy. Thus, the goal is to examine the effects of a novel slow release E2-loaded nanoparticle (SNP-E2) gel
patch on neuronal dysfunction and skeletal muscle loss in a rat model of SCI. We hypothesize that focal delivery
of estrogen via slow release nanoparticles SNP-E2 will maintain low systemic E2 levels (plasma) and higher
tissue concentrations, thereby allowing for maximized therapeutic potential for recovery from neural and skeletal
muscle loss in SCI. To test the hypothesis, two specific aims are proposed: (Aim 1) Examine the delivery of a
novel slow release SNP-E2 and determine its kinetics, bio-distribution, toxicity, and effects in moderate and
severe SCI and (Aim 2) Determine the effects of SNP-E2 on alterations of skeletal muscle loss in moderate and
severe SCI. Overall, the proposed studies should provide a safe and novel strategy to improve health and
functional recovery for Veterans with SCI.
Parkinson’s disease (PD) is a progressive degenerative disorder affecting almost 80,000 Veterans. While
the mechanisms of this degenerative process remain elusive, chronic inflammation may be involved. Calpain
not only plays a pivotal role in brain (SN-DA neurons) and spinal cord (SC) degeneration, it may also drive
inflammation and disease progression. Inhibition of calpain attenuates a distinct subpopulation of T cells in
MPTP mice, suggesting calpain’s involvement in the inflammatory process. Our goal is to develop therapeutic
strategies to treat PD with agents that block the inflammatory process, protect neurons, control disease
progression, and improve function. We hypothesize that calpain activation, infiltration of inflammatory T cells
(Th1/Th17), and released cytokines and chemokines are involved in progressive degeneration of PD, and calpain
inhibitor treatment may reduce degeneration, slow disease progression, and improve function. Two specific aims
will test the hypothesis: (Aim 1) Investigate the role of calpain regulation and T cell infiltration in SC degeneration
and disease progression in MPTP mice, characterize infiltrating T cells, assess cytokine/chemokine levels in
sera, and determine cell death parameters and calpain activation in SC; (Aim 2) Examine whether treatment of
MPTP mice with calpain inhibitor will reduce degenerative inflammatory events and improve function.
Increased calpain activity has also been found in MS as well as in its animal model [experimental autoimmune
disease (EAE)], and calpain is implicated in the activation of T cells (Th1/Th17), degradation of axon/myelin, and
T cell chemotaxis. While calpain is activated in brain and spinal cord of MS patients, the precise involvement of
the two calpain isoforms, calpain-1 and calpain-2, remains undefined. We hypothesize that activation of distinct
calpain isoform may favor expansion of inflammatory mediators and Th1/Th17 cells in MS patients, which could
be attenuated by calpain inhibition. Studies include (Aim 1) testing MS patient samples to determine which of
the two major calpain isoforms is involved in dysregulation of immune cell types, influencing immune arms of the
disease; and (Aim 2) Investigating whether a distinct calpain isoform is linked with disease progression, influ-
encing the neurodegenerative process in MS. Data obtained will reveal the effect of calpain inhibitor on inhibition
of specific calpains and attenuation of both immune and neurodegenerative arms of the disease for developing
novel therapy for treating MS and other neurodegenerative diseases. The overall goal of these research projects
is to minimize degeneration and maximize function and improve the health of our Veterans.

Grant Number: 5IK6BX005964-04
NIH Institute/Center: VA
Principal Investigator: NAREN BANIK