Preclinical Pipeline

MSC-NTF cells have been studied in a variety of animal models of neurodegenerative diseases; some of these key findings are summarized below.

Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disorder that affects the brain and spinal cord. Neurons are normally insulated with a protective layer called myelin, which allows nerve signals to travel properly. In MS, the myelin is destroyed, and demyelinated neurons cannot function properly. While generally thought to be an autoimmune disease, the exact cause of MS is unknown.

Distinctions

There are two distinct presentations of MS, most patients are initially diagnosed with relapsing-remitting disease, which goes through cycles of activity followed by quiet periods, while others present with progressive disease.  For many patients with relapsing-remitting MS, the disease will eventually become progressive.  There are many approved therapies for relapsing-remitting MS, but patients with progressive disease have few treatment options.  Over 2.5 million people around the world live with MS.

Relapsing-remitting multiple sclerosis is commonly studied in the mouse autoimmune encephalitis (EAE) model, in which the mouse immune system attacks myelin proteins.  We transplanted MSC-NTF and MSCs cells into EAE mice, via intracerebroventricular administration, which delayed symptom onset and improved survival. Transplantation of MSCs also exerted a positive effect but to a lesser extent.  These results indicated that MSC-NTF cells are active in the mouse EAE model, potentially acting through neuroprotective and immunomodulatory mechanisms (Barhum et al, J Mol Neuroscience 2009).

Parkinson’s Disease

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder that affects neurons in the brain that produce dopamine, a chemical messenger (neurotransmitter) that directs and controls movement. In PD, these dopamine-producing nerve cells break down, causing dopamine levels to drop and brain signals that direct movement to become abnormal. The cause of the disease is unknown.  There are approximately 7-10 million PD patients worldwide.  Current drug treatment options for PD patients focus on treating the disease’s symptoms and are based on dopamine replacement or prevention of dopamine breakdown. With prolonged use, these drugs have serious negative side effects.

The neuroprotective effects of MSC-NTF cells were tested in the 6-OHDA mouse model of PD that uses the neurotoxin 6hydroxydopamine to destroy dopaminergic neurons. MSC-NTF cells were transplanted into the striatum, a brain structure affected in these mice, and they improved performance of the mice on rotarod testing and inhibited dopamine depletion in the striatum. MSC-NTF cells were found to migrate to the site of damaged neurons in the striatum and induced regeneration of neurons (Sadan O et al. 2009).

Huntington`s Disease

Huntington’s disease (HD) is a hereditary, progressive disabling and ultimately fatal neurodegenerative disorder.  Although some treatments are available for controlling symptoms, there are no approved therapies that alter the disease course.  The prevalence of HD worldwide is approximately 5-10 per 100,000, and is found more commonly in people with a Western European genetic background. We studied MSC-NTF cells in both the quinolinic acid rat model and the R6/2 transgenic mouse model of HD.  After administration of QA into the striatum, we transplanted cells into the same area (Sadan O et al. 2012a, 2012b). MSC-NTF cells were found six weeks after administration and continued to secrete BDNF and GDNF.  The cells preserved the striatum and caused behavioral improvements in the treated animals.

Autism Spectrum Disorder

Autism spectrum disorder is a complicated and poorly understood disorder of brain development characterized by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. Approximately 1% of the world population falls under the spectrum and while behavioral therapy can produce meaningful benefits in autism patients, there are no drugs approved to treat the disorder.  We have studied MSC-NTF cells in the BTBR mouse strain, which exhibits several behaviors that resemble behaviors seen in autism spectrum disorders, including repetitive behaviors, altered social interactions, cognitive rigidity and impaired adaption to environment. Across a variety of measures, including assessments of repeated self-grooming, social interaction and cognitive rigidity, MSC-NTF cells caused behavioral and cognitive benefits in BTBR mice after a single treatment compared to control mice.  See our January 26, 2015 press release for details.

Peripheral Nerve Injury

We studied MSC-NTF cells in the unilateral Sprague-Dawley rat Sciatic Nerve Injury model.  Sciatic nerves are the longest and largest single nerves in the body. They begin in the lower spinal cord and run through the pelvis and down the lower limb and innervate the back of the thigh, leg and foot muscles. Four days after the cells were transplanted into rats with damaged sciatic nerves, motor function and nerve conduction measured by rotarod was found to be markedly preserved in the rats injected with the MSC-NTF cells (Dadon-Nachum M et al 2011).   MSC-NTF cells were also able to protect retinal ganglion cells from degeneration and death following optic nerve transection (Levkovitch-Verbin H et al. 2010).