Non-surgical transplantation of motor neuron-differentiated stem cells: A novel approach to the treatment of ALS

2015  -  Toronto, ON, CA


Toronto Western Hospital

Project description

There is significant interest in the development of cellular replacement therapy for the treatment of Amyotrophic Lateral Sclerosis (Lou Geherig’s disease or ‘ALS’), a terminal illness that is associated with a progressive decline in motor function leading to death-often within three years of diagnosis.  In this project we will build upon our pilot studies and obtain stem cells from articular cartilage, pre-differentiate them into neural cells and then using MRI guided focused ultrasound technology, transplant these cells into the spinal cord of a mouse that develops an ALS-like disease.  Our pilot studies have shown that these transplanted cartilage-derived stem cells (CDSCs) assume neuronal, astrocyte and oligodendrocyte fate-cells that are vital for spinal cord function and that these cells develop connections with muscle fibres in laboratory culture suggesting that they are functionally active.

We will test the function of the ALS-afflicted mice (SOD1 mutant mice) after transplant and determine the ability of the transplanted cells to influence the course of the illness.  We will characterize the effects of the transplanted cells in terms of cellular differentiation, influence upon spinal cord health and if successful, lead to an application for a clinical trial in humans.

Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging

Our approach will for the first time, effect the non-surgical transplant of neural-differentiated stem cells creating the possibility for multiple transplant procedures where only a single, highly invasive surgical procedure was available.  If this approach successfully ameliorates disease progression in the mutant mice, it will pave the way for early clinical trials in humans.  Our method of non-surgical transplantation will avoid the significant morbidity and risks of mortality associated with the extensive surgical procedures otherwise required to transplant cells into the spinal cord of patients living with ALS and might enable multiple transplants-a hitherto impossibility due to the limitation imposed by historical methods of transplantation.

Anticipated outcome

We will demonstrate the effects of cellular replacement within the spinal cord of an animal (G93A SOD1 mouse) that displays the characteristics of approximately 20% of familial ALS patients. Specifically, we will determine the influence of a single MRIgfUS transplant procedure upon disease progression, survival and the cellular and morphological characteristics of the diseased spinal cord.  We hypothesize that the transplant of health cells will confer increased survival on the part of the transplant recipients leading to a clinical trial in humans.  This stem cell source and technology could be harnessed in the treatment of other neural repair strategies.