Multiple Sclerosis

Coding Dimension ID: 
311
Coding Dimension path name: 
Neurological Disorders / Multiple Sclerosis
Disease Fact Sheet Page: 
/our-progress/disease-information/multiple-sclerosis-fact-sheet
Grant Type: 
Early Translational III
Grant Number: 
TR3-05603
Investigator: 
Type: 
PI
Type: 
Co-PI
Institution: 
Type: 
Partner-PI
ICOC Funds Committed: 
$4 799 814
Disease Focus: 
Multiple Sclerosis
Neurological Disorders
Collaborative Funder: 
Australia
Human Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
oldStatus: 
Active
Public Abstract: 

Multiple Sclerosis (MS) is a disease of the central nervous system (CNS) caused by inflammation and loss of cells that produce myelin, which normally insulates and protects nerve cells. MS is a leading cause of neurological disability among young adults in North America. Current treatments for MS include drugs such as interferons and corticosteroids that modulate the ability of immune system cells to invade the CNS. These therapies often have unsatisfactory outcomes, with continued progression of neurologic disability over time. This is most likely due to irreversible tissue injury resulting from permanent loss of myelin and nerve destruction. The limited ability of the body to repair damaged nerve tissue highlights a critically important and unmet need for MS patients. The long-term goal of our research is to develop a stem cell-based therapy that will not only halt ongoing loss of myelin but also lead to remyelination and repair of damaged nerve tissue. Our preliminary data in animal models of human MS are very promising and suggest that this goal is possible. Research efforts will concentrate on refining techniques for production and rigorous quality control of clinically-compatible transplantable cells generated from high-quality human pluripotent stem cell lines, and to verify the therapeutic activity of these cells. We will emphasize safety and development of the most therapeutically beneficial cell type for eventual use in patients with MS.

Statement of Benefit to California: 

One in seven Americans lives in California, and these people make up the single largest health care market in the United States. The diseases and injuries that affect Californians affect the rest of the US and the world. Many of these diseases involve degeneration of healthy cells and tissues, including neuronal tissue in diseases such as Multiple Sclerosis (MS). The best estimates indicate that there are 400,000 people diagnosed with MS in the USA and 2.2 million worldwide. In California, there are approximately 160,000 people with MS – roughly half of MS patients in the US live in California. MS is a life-long, chronic disease diagnosed primarily in young adults who have a virtually normal life expectancy but suffer from progressive loss of motor and cognitive function. Consequently, the economic, social and medical costs associated with the disease are significant. Estimates place the annual cost of MS in the United States in the billions of dollars. The development of a stem cell therapy for treatment of MS patients will not only alleviate ongoing suffering but also allow people afflicted with this disease to return to work and contribute to the economic stabilization of California. Moreover, a stem cell-based therapy that will provide sustained recovery will reduce recurrence and the ever-growing cost burden to the California medical community.

Grant Type: 
Early Translational III
Grant Number: 
TR3-05617
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$4 327 175
Disease Focus: 
Multiple Sclerosis
Neurological Disorders
Human Stem Cell Use: 
Adult Stem Cell
Cell Line Generation: 
Adult Stem Cell
oldStatus: 
Active
Public Abstract: 

Multiple sclerosis (MS) is an autoimmune disease in which the myelin sheath that insulates neurons is destroyed, resulting in loss of proper neuronal function. Existing treatments for MS are based on strategies that suppress the immune response. While these drugs do provide benefit by reducing relapses and delaying progression (but have significant side effects), the disease invariably progresses. We are pursuing an alternative therapy aimed at regeneration of the myelin sheath through drugs that act on an endogenous stem cell population in the central nervous system termed oligodendrocyte precursor cells (OPCs). Remission in MS is largely dependent upon OPCs migrating to sites of injury and subsequently differentiating into oligodendrocytes – the cells that synthesize myelin and are capable of neuronal repair. Previous studies indicate that in progressive MS, OPCs are abundantly present at sites of damage but fail to differentiate to oligodendrocytes. As such, drug-like molecules capable of inducing OPC differentiation should have significant potential, used alone or in combination with existing immunomodulatory agents, for the treatment of MS. The objective of this project is to identify a development candidate (DC) for the treatment of multiple sclerosis (MS) that functions by directly stimulating the differentiation of the adult stem cells required for remyelination.

Statement of Benefit to California: 

Multiple Sclerosis (MS) is a painful, neurodegenerative disease that leads to an impairment of physical and cognitive abilities. Patients with MS are often forced to stop working because their condition becomes so limiting. MS can interfere with a patient's ability to even perform simple routine daily activities, resulting in a decreased quality of life. Existing treatments for MS delay disease progression and minimize symptoms, however, the disease invariably progresses to a state of chronic demyelination. The goal of this project is to identify novel promyelinating drugs, based on differentiation of an endogenous stem cell population. Such drugs would be used in combination with existing immunosuppressive drugs to prevent disease progression and restore proper neuronal activity. More effective MS treatment strategies represent a major unmet medical need that could impact the roughly 50,000 Californians suffering from this disease. Clearly the development of a promyelinating therapeutic would have a significant impact on the well-being of Californians and reduce the negative economic impact on the state resulting from this degenerative disease.

Grant Type: 
Comprehensive Grant
Grant Number: 
RC1-00135
Investigator: 
ICOC Funds Committed: 
$2 566 701
Disease Focus: 
Immune Disease
Multiple Sclerosis
Neurological Disorders
Stroke
Human Stem Cell Use: 
Adult Stem Cell
Embryonic Stem Cell
oldStatus: 
Closed
Public Abstract: 

Strokes that affect the nerves cells, i.e., “gray matter”, consistently receive the most attention. However, the kind of strokes that affecting the “wiring” of the brain, i.e., “white matter”, cause nearly as much disability. The most severe disability is caused when the stroke is in the wiring (axons) that connect the brain and spinal cord; as many as 150,000 patients are disabled per year in the US from this type of stroke. Although oligodendrocytes (“oligos”) are the white matter cells that produce the lipid rich axonal insulator called myelin) are preferentially damaged during these events, stem cell-derived oligos have not been tested for their efficacy in preclinical (animal) trials. These same white matter tracts (located underneath the gray matter, called subcortical) are also the primary sites of injury in MS, where multifocal inflammatory attack is responsible for stripping the insulating myelin sheaths from axons resulting in axonal dysfunction and degeneration. Attempts to treat MS-like lesions in animals using undifferentiated stem cell transplants are promising, but most evidence suggests that these approaches work by changing the inflammation response (immunomodulation) rather than myelin regeneration. While immunomodulation is unlikely to be sufficient to treat the disease completely, MS may not be amenable to localized oligo transplantation since it is such a multifocal process. This has led to new emphasis on approaches designed to maximize the response of endogenous oligo precursors that may be able to regenerate myelin if stimulated. We hypothesize that by exploiting novel features of oligo differentiation in vitro (that we have discovered and that are described in our preliminary data) that we will be able to improve our ability to generate oligo lineage cells from human embryonic stem cells and neural stem cells for transplantation, and also to develop approaches to maximize oligo development from endogenous precursors at the site of injury in the brain. This proposal will build on our recent successes in driving oligo precursor production from multipotential mouse neural stem cells by expressing regulatory transcription factors, and apply this approach to human embryonic and neural stem cells to produce cells that will be tested for their ability to ameliorate brain damage in rodent models of human stroke. Furthermore, we hope to develop approaches that may facilitate endogenous recruitment of oligo precursors to produce mature oligos, which may prove a viable regenerative approach to treat a variety of white matter diseases including MS and stroke.

Statement of Benefit to California: 

Diseases associated with disruption of oligodendrocyte function and integrity (such as subcortical ischemic stroke and multiple sclerosis) are major causes of morbidity and mortality. Stroke is the third leading cause of death and the leading cause of permanent disability in the United States, costing over $50 billion dollars annually, as approximately 150,000 chronic stroke patients survive the acute event and are left with permanent, severe motor and/or sensory deficits. While much less common, multiple sclerosis (MS) is the primary non-traumatic cause of neurologic disability in young adults. Most patients are diagnosed in their 20s-40s and live for many decades after diagnosis with increasing needs for expensive services, medications and ultimately long-term care. Existing strategies for stem cell based therapies include both strategies to replace lost cells and to augment regeneration after injury, but most of these efforts have emphasized the role of undifferentiated stem cells in treatment despite the realization that the main nexus of injury in both diseases is frequently a differentiated cell type – the oligodendrocyte. This project will use new insights into the development of oligodendrocytes from the laboratories of the investigators to find ways to improve production of oligodendrocytes from human ES cells and human neural stem cells, test whether these cells can improve the clinical outcome in rodent models of stroke and MS after transplantation and search for new molecular treatments that would augment the regeneration of oligodendrocytes from resident brain stem cells after injury. This is the first step to translating the basic fundamental understanding of oligodendrocyte development into viable therapies for important human diseases that are major burdens on the citizens of California.

Grant Type: 
SEED Grant
Grant Number: 
RS1-00409
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$425 594
Disease Focus: 
Immune Disease
Multiple Sclerosis
Neurological Disorders
Human Stem Cell Use: 
Embryonic Stem Cell
oldStatus: 
Closed
Public Abstract: 

Multiple sclerosis (MS) is the most common neurologic disease affecting young adults under the age of 40 with the majority of MS patients diagnosed in the second or third decade of life. MS is characterized by the gradual loss of the myelin sheath that surrounds and insulates axons that allow for the conduction of nerve impulses – a process known as demyelination. For unknown reasons, the ability to remyelinate axons is impaired in MS patients making recovery of motor skills difficult. Therefore, developing novel and effective approaches to remyelinate axons in MS patients would dramatically improve the quality of life of many MS patients. The experiments described in this research proposal utilize a well-accepted model of MS to further characterize the potential clinical applicability of human embryonic stem cells (hESCs) to remyelinate axons. Such knowledge is crucial in order to increase our understanding of stem cells with regards to treatment of numerous human diseases including MS.

Statement of Benefit to California: 

California is the most populated state in the USA. As such, the costs of medical care for the treatment of patients with chronic diseases such as multiple sclerosis (MS) represents a significant and growing problem. MS is the most common neurologic disease affecting young adults under the age of 40 with the majority of MS patients diagnosed in the second or third decade of life. Given the population of California, there are many MS patients living in the state and the numbers will undoubtedly grow. It is unusual for MS patients to die from the disease and many will live normal life spans but will develop an increasing array of medical problems stemming from the progression of neurologic damage associated with MS. MS is characterized by the gradual loss of the myelin sheath that surrounds and insulates axons that allow for the conduction of nerve impulses – a process known as demyelination. For unknown reasons, the ability to remyelinate axons is impaired in MS patients making recovery of motor skills difficult. Therefore, developing novel and effective approaches to remyelinate axons in MS patients would dramatically alleviate some of the burden placed on the medical community by improving the quality of life of many MS patients. The experiments described in this research proposal utilize a well-accepted model of MS to further characterize the potential clinical applicability of human embryonic stem cells (hESCs) to remyelinate axons. Such knowledge is crucial in order to increase our understanding of stem cells with regards to treatment of human diseases with the ultimate goal of limiting patient suffering and reducing medical costs.