Stem cells are unspecialized cells that have the remarkable potential to develop into many different cell types in the body (such as a muscle cell, a liver cell, or a brain cell) as well as divide to make more stem cells. They play a fundamental role in embryo development and later on in development of organs and tissues. Stem cells continue to function throughout a person’s life and they can theoretically divide without limit to replenish other cells in the body. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function.

There are many areas in medicine in which stem cell research could have a tremendous impact. There are a variety of diseases and injuries in which a patient’s cells or tissues are damaged and must be replaced by transplants. Stem cells have an ability to generate brand new tissue in these patients and may be able to cure diseases for which currently there is no adequate therapy. Some diseases that scientist believe stem cell therapy would help include Alzheimer’s and Parkinson’s disease, diabetes, spinal cord injury, heart disease, stroke, arthritis, skin burns and even cancer. New research suggests that causes of at least several cancers are mutated stem cells (cancer stem cells).

Because stem cells can be used to create limitless amounts of specialized tissue, they can be used in the testing and development of new drugs before trying the drugs on animals or human subjects.

Stem cells can also be used to gain a better understanding of how genetics work in the early stages of cell development and how certain abnormalities lead to birth defects and cancer. By understanding the genetic basis for cell development, scientists may learn how to prevent some types of diseases.

All stem cells are characterized by the ability to self-replicate (make themselves) and the ability to turn into other cell types. However, there are two main categories of stem cells, embryonic and adult.

Embryonic stem (ES) cells are undifferentiated, pluripotent, and derived from morula or blastocysts from fertilized eggs. These eggs are left over from the in vitro fertilization (IVF) process and otherwise scheduled for destruction. Embryonic stem cells can turn into almost any cell type in the body; this is known as pluripotency.

As ES cells grow and mature, they begin to differentiate into more specific cell types. At this point cells have a more limited potential, and therefore are referred to as multipotent. Adult stem cells are undifferentiated, multipotent, and found in tissue or organs with differentiated cells. These are not as versatile for research purposes.

Much research in recent years has focused on developing methods to convert multipotent cell types into a more pluripotent, embryonic stem cell-like state. Induced pluripotent stem cells (iPSCs) are adult stem cells which have been reprogrammed to share many of the key properties of pluripotent embryonic stem cells. iPSCs have already demonstrated success as tools for drug development and disease modelling, and hold the promise to become clinically relevant in the future.

California Stem Cell is currently investigating the use of human ES cells, human iPSCs, and cancer stem cells in developing treatments for SMA, ALS, and malignant cancers.

Embryonic stem cell lines (ES cell lines) are cultures of cells derived from donated fertilized eggs leftover from the in vitro fertilization process which were otherwise scheduled for destruction. The cells themselves are derived from the inner cell mass (ICM) of blastocysts or other early stage post-zygotic structures. ES cells have an ability to develop into more than 200 different cell types of the adult body when given proper stimulation.

Human embryonic stem cells (hESCs) were first derived in 1998 by James Thompson at the University of Wisconsin. Large numbers of embryonic stem cells can now be easily grown in culture, whereas adult stem cells are rare in mature tissues, and methods for isolating those cells and expanding their numbers in cell culture have not yet been perfected. This is significant, as large numbers of cells are needed for stem cell replacement therapies, making hESCs the ideal candidate for such a use. In the future, iPSCs derived from a patient’s own cells could potentially be expanded in culture to clinically relevant numbers, and reintroduced into the patient without being rejected, thus combining the benefits of hESC and adult stem cells in the clinical application.

Umbilical cord blood stem cells are present in umbilical cord blood at birth. These stem cells are multipotent and more versatile than adult stem cells, but do not have the same capacity to become any type of cell as do embryonic stem cells.

The advantage of using cord blood stem cells is that they are virtually effortless to collect and free from any risks to the baby or mother.

The disadvantage of cord blood stem cells is that there are relatively few numbers of them available in the cord blood and they do not grow as well in culture as hESCs. This makes working with cord blood stem cells harder. Umbilical cord blood stem cell transplants are currently being used to treat leukemia and other blood disorders.

California Stem Cell does not currently use cord blood cells in any of its therapeutic research.

Cell replacement therapies have been shown to have applications in many diseases and disorders characterized by the loss of cellular material and tissues which cannot be self-regenerated by the human body. These include diseases of the nervous system, cancer, cardiac disorders (myocardial infarction and heart failure), diabetes mellitus, diseases of bones and joints, genetic disorders, and wounds of the skin and soft tissues.

Cell replacement therapy effectively works to reconstitute and repair lost or damaged tissue through the transplantation of functional cell material, restoring a degree of function to the damaged areas.^{[1]Zietlow R, Lane EL, Dunnett SB, Rosser AE. Human stem cells for CNS repair. Cell Tissue Res. 2008. Jan;331(1):301-22.[2]Rosser AE, Zietlow R, Dunnett SB. Stem cell transplantation for neurodegenerative diseases. Curr Opin Neurol. 2007 Dec;20(6):688-92.[3]Lindvall O. Why is it taking so long to develop clinically competitive stem cell therapies for CNS disorders? Cell Stem Cell. 2012 Jun 14;10(6):660-2. doi: 10.1016/j.stem.2012.04.004.[4]Weissman IL. Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science. 2000 Feb 25;287(5457):1442-6.}

Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a progressive neurodegenerative disease for which there is no cure. It affects motor neurons in the brain and spinal cord that control voluntary muscle movement. Progressive degeneration of motor neurons in ALS results in death of motor neurons and loss of voluntary muscle control.

Onset of ALS is usually in adulthood and the disease progresses rapidly, starting with generalized muscle weakness and wasting, but ultimately resulting in total paralysis. Average survival after diagnosis is 3 to 5 years, with death usually a result of respiratory complications.

The exact causes of ALS are unknown. Most cases are sporadic, but 5-10% of cases are familial. Approximately 30,000 people throughout the U.S. currently have ALS, and 5,000 new cases are diagnosed each year. ALS occurs in individuals of all ages, sexes and races.^{[5] Naganska E, Matyja E. Amyotrophic lateral sclerosis – looking for pathogenesis and effective therapy. Folia Neuropathol. 2011;49(1):1-13.[6]Alsa.org. “Who Gets ALS? – The ALS Association.” N.p., 2011. Web. 26 Oct 2012. [http://www.alsa.org/about-als/who-gets-als.html].}

California Stem Cell (CSC) is in pre-clinical development of a potential stem cell-derived therapy for ALS.

If you are seeking more information or support options for ALS, please visit:

MDA-ALS
Muscular Dystrophy Association’s ALS Division is the world leader among voluntary agencies fighting ALS, offering the most comprehensive range of services. People with ALS receive care at 225 MDA-supported ALS clinical centers across the country. MDA also leads the search for a treatment or cure for ALS through its aggressive, worldwide research program.

ALSA
ALS Association is the only national not-for-profit health organization dedicated solely to the fight against ALS. The Association leads the way in research, patient and community services, public education, and advocacy – giving help and hope to those facing the disease. The Association’s nationwide network of chapters provides comprehensive patient services and support to the ALS community.

Spinal Muscular Atrophy (SMA) is a genetic neuromuscular disorder for which there is no cure. It is a result of a missing or mutated gene and affects the voluntary muscles throughout the body. This disease affects 1 in 6000 babies born and about 1 in 40 people are genetic carriers. It is one of the most prevalent genetic disorders and can affect individuals of any age, race or gender.^{[7]D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis. 2011 Nov 2;6:71.[8]FSMA.org. “What Causes SMA? – Families of SMA.” N.p. 2012. Web. 26 Oct 2012. [http://www.fsma.org/FSMACommunity/understandingsma/WhatCausesSMA/]}

Individuals with SMA have difficulty with activities such as crawling, walking, controlling the head and neck, and swallowing. They have weakness in limbs, with legs generally more affected than arms, and difficulty feeding and swallowing. Patients also have an increased risk of developing pneumonia and other lung problems due to involvement of respiratory muscles. Sensation is not affected and intellectual activity is normal.

SMA is an autosomal recessive genetic disease. This means that in order for a child to be affected, both parents must be carriers of the abnormal gene and both must pass this gene onto their child. If both parents are carriers, there is a 25% chance of the child inheriting the disease.

The missing or mutated gene is SMA is called survival motor neuron 1 (SMN1), which produces a protein called Survival Motor Neuron (SMN) protein. This protein is critical to the survival and health of motor neurons, which are nerve cells in the spinal cord that send out nerve fibers to muscles throughout the body. Without SMN, nerve cells atrophy and eventually die, resulting in muscle weakness.

There are four types of SMA and patients are classified into each type based on the physical milestones achieved at the onset of the disease. Type I and II are the most prevalent.

• SMA Type I
  Type I, or Werdnig-Hoffmann Disease, is the most severe form of SMA. It strikes infants between birth and six months old. Children affected with Type I cannot sit without support. SMA Type I can progress very rapidly, leading to early childhood death.
• SMA Type II
  Type II affects infants between seven and 18 months old. Patients may be able to sit unaided or even stand with support. They are at increased risk for complications from respiratory infections. SMA Type II usually progresses slowly and survival into adulthood is common.
• SMA Type III
  Type III, also known as Kugelberg-Welander Disease, is the least deadly form of childhood-onset SMA. It strikes children as early as the age of 18 months, but can surface as late as adolescence. Type III patients are able to walk, but weakness is prevalent. Most patients eventually need to use a wheelchair. SMA Type III progresses slowly and life span is usually not affected.
• SMA Type IV
  Type IV is the adult form of the disease. Symptoms tend to begin after age 35 and muscles used for swallowing and respiratory function are rarely affected. SMA Type IV has very slow progression and life span is usually not affected.

Typically, patients with SMA have continued loss of motor function over time. SMA does not affect sensation and intellectual activity in patients.

Since filing its Investigational New Drug (IND) application with the US FDA in late 2010, CSC has been working closely with the FDA to begin the first-ever Phase I clinical study of stem cell therapies in SMA Type I patients.

If you are seeking more information or support options for SMA, please visit:

Families of SMA
Families of Spinal Muscular Atrophy is dedicated to advancing research and supporting all those affected by SMA. Families of SMA is a great source of information and support to families dealing with this devastating disease. We will conduct any SMA trials in collaboration with the Families of SMA and encourage anyone interested to use the International SMA Patient Registry.

MDA
The Muscular Dystrophy Association is a voluntary health agency — a dedicated partnership between scientists and concerned citizens aimed at conquering neuromuscular diseases that affect more than a million Americans.

Fight SMA
Fight SMA is an international nonprofit organization dedicated to finding a treatment or cure for spinal muscular atrophy. Fight SMA works to bring higher levels of awareness and understanding to SMA.

Spinal cord injury (SCI) is a disorder for which there is no cure. Major functional deficit results from motor neuron loss and affects 450,000 individuals in the U.S, with 11,000 new injuries per year. Most cases result in permanent disability or paralysis below the location of injury. There is currently no way to reverse the damage to the spinal cord.^{[9] National Spinal Cord Statistical Center. “Spinal Cord Injury Facts and Figures at a Glance – NSCISC” N.p. 2012. Web 26 Oct 2012.
[https://www.nscisc.uab.edu/.../Facts%202012%20Feb%20Final.pdf].}

This disorder affects men disproportionately to women, and 60% of cases are seen in individuals under the age of 30. The most common causes of spinal cord injury are motor vehicle accidents, sports injuries, falls, acts of violence, and disease.^{[9] National Spinal Cord Statistical Center. “Spinal Cord Injury Facts and Figures at a Glance – NSCISC” N.p. 2012. Web 26 Oct 2012.
[https://www.nscisc.uab.edu/.../Facts%202012%20Feb%20Final.pdf].}

Individuals with spinal cord injury often have medical complications such as pressure sores, chronic pain, bladder and bowel dysfunction, along with an increased susceptibility to respiratory and heart problems.

If you are seeking more information or support options for SCI, please visit:

National Spinal Cord Injury Association
National Spinal Cord Injury Association (NSCIA) is the nation’s oldest and largest civilian organization dedicated to improving the quality of life for hundreds of thousands of Americans living with the results of spinal cord injury and disease and their families. NSCIA educates and empowers survivors of spinal cord injury and disease to achieve and maintain the highest levels of independence, health and personal fulfillment.

For a treatment or drug to be made available on the U.S. market it must first obtain approval by the FDA (Food and Drug Administration). Before a treatment or drug can be approved, it must first go through several phases of clinical trials in order to ensure safety and efficacy.

Pre-clinical Studies

Initial studies are done to collect data from laboratory and animal tests in order to determine preliminary safety and efficacy information on a drug or treatment. This step allows a company to determine if it is worthwhile moving forward with the proposed treatment.

Investigational New Drug Application

If a company decides to move forward with a proposed treatment following promising pre-clinical study results, it must file an Investigational New Drug Application (IND) with the FDA. Included in this application are animal pharmacology and toxicology studies, chemical and manufacturing information, proposed clinical protocols, and information on clinical investigators that will be conducting the trials.

Phase I Trials

Phase I trials are the first studies in humans and typically enroll only a small number of subjects. Trials are conducted in order to determine safety in humans, safe dosage range, and any possible side effects. If the treatment is safe and tolerated well by the subjects, it can move onto Phase II trials.

Phase II Trials

Phase II trials include many more volunteers and are conducted to determine if treatment is effective and to further evaluate its safety. If treatment is safe and effective it moves onto Phase III trials.

Phase III Trials

Phase III trials are done to determine how effective the new treatment is compared to the existing standard treatment and also to monitor side effects. These trials involve large groups of patients and typically have a long duration.

Phase IV Trials

This phase, also called Post Marketing Surveillance, takes place after FDA approval and the treatment is available on the market for use. This phase provides for continuing evaluation of the treatment’s side effect on larger populations and after long-term use.

New Drug Application

Once efficacy of a drug or treatment has been demonstrated through clinical trials, the company files a New Drug Application (NDA) with the FDA for permission to market and sell the treatment in the U.S. All the data collected from animal studies and human clinical trials becomes part of the NDA.

California Stem Cell Progress

Since filing its Investigational New Drug (IND) application with the US FDA in late 2010, CSC has been working closely with the FDA to begin the first-ever Phase I clinical study of stem cell therapies in SMA Type I patients. Applications for ALS are currently in pre-clinical development. Patient accrual for California Stem Cell’s Phase II patient-specific cancer immunotherapy has concluded; preparation and design of a multi-institutional phase III clinical trial is now under way.