Today, most treatments for damage to the brain or spinal cord aim to relieve symptoms and limit further damage. But recent research into the regeneration mechanisms of the central nervous system, including the discovery of stem cells in the adult brain that can give rise to new neurons and neural support cells, has raised hopes that researchers can find ways to actually repair central nervous system damage.
In the mid-1990s, neuroscientists learned that some parts of the adult human brain do, in fact, generate new neurons, at least under certain circumstances. Moreover, they found that the new neurons arise from “neural stem cells” in the fetal as well as the adult brain. These undifferentiated cells resemble cells in a developing fetus that give rise to the brain and spinal cord. The researchers also found that these neural stem cells could generate many, if not all, types of cells found in the brain. This includes neurons as well as crucial neural-support cells called oligodendrocytes and astrocytes. The discovery of a regenerative capacity in the adult central nervous system holds out the promise that it may eventually be possible to repair damage from terrible degenerative diseases such as Parkinson’s Disease and amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), Huntington’s Disease as well as from brain and spinal cord injuries resulting from stroke or trauma.
Diseases of the nervous system, including congenital disorders, cancers, and degenerative diseases, affect millions of people of all ages. Congenital disorders occur when the brain or spinal cord does not form correctly during development. Cancers of the nervous system result from the uncontrolled spread of aberrant cells. Degenerative diseases occur when the nervous system loses functioning of nerve cells. Most of the advances in stem cell research have been directed at treating degenerative diseases.
Researchers are pursuing two fundamental strategies to exploit this discovery. One is to grow differentiated cells in a laboratory dish that are suitable for implantation into a patient by starting with undifferentiated neural cells or to implant them directly and rely on signals inside the body to direct their maturation into the right kind of brain cell. The other repair strategy relies on finding growth hormones and other “trophic factors” growth factors, hormones, and other signaling molecules that help cells survive and grow that can fire up a patient’s own stem cells and endogenous repair mechanisms, to allow the body to cope with damage from disease or injury.
Using Stem Cells in Treating Parkinson’s Disease Research
Parkinson’s is a progressive movement disorder that usually strikes after age 50. Symptoms often begin with an uncontrollable hand tremor, followed by increasing rigidity, difficulty walking, and trouble initiating voluntary movement. The symptoms result from the death of a particular set of neurons deep in the brain. Most patients suffering from Parkinson’s Disease are treated with a drug called levodopa. It initially helps most patients, but unfortunately, side effects of the drug increase over time and its effectiveness wanes. Fully developed and differentiated dopamine neurons do not survive transplantation, so direct transplantation of fully developed brain tissue is not an option.
Transplanting developing dopamine neurons from fetal brain tissue studies showed encouraging, but inconsistent, benefit to patients. The logistical and technical problems involved in recovering enough developing dopamine neurons from fetal tissue are very great. Most researchers are also convinced they must find a different source of cells for transplant.
Neural stem cells isolated from animals and humans cannot be grown efficiently in the lab without changing them in some way, such as by engineering them to express a gene normally turned on only early in development. Cells with features of neural stem cells have been derived from ES-cells, fetal brain tissue, brain tissue from neurosurgery, and brain tissue that was obtained after a person’s death. If researchers want to be able to implant cells derived from undifferentiated embryonic stem cells, they must take care that no cells in the mix give rise to unwanted cell types, such as muscle or bone, within the nervous system. Recent studies, however, suggest that ES cells may differentiate into neurons in a more straightforward manner than may other cell types.
Possibilities for Sten Cells in the Treatment of Other Nervous Syatem Disorders
Many other diseases that affect the nervous system hold the potential for being treated with stem cells. Experimental therapies for chronic diseases of the nervous system, such as Alzheimer’s disease, Lou Gehrig’s disease, or Huntington’s disease, and for acute injuries, such as spinal cord and brain trauma or stoke, are being currently developed and tested. These diverse disorders must be investigated within the contexts of their unique disease processes and treated accordingly with highly adapted cell-based approaches.
Although severe spinal cord injury is an area of intense research, the therapeutic targets are not as clear-cut as in Parkinson’s disease. Spinal cord trauma destroys numerous cell types, including the neurons that carry messages between the brain and the rest of the body. In many spinal injuries, the cord is not actually severed, and at least some of the signal-carrying neuronal axons remain intact. However, the surviving axons no longer carry messages because oligodendrocytes, which make the axons’ insulating myelin sheath, are lost. Getting neurons to grow new axons through the injury site to reconnect with their targets is even more challenging.
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is characterized by a progressive destruction of motor neurons in the spinal cord. Patients with ALS develop increasing muscle weakness over time, which ultimately leads to paralysis and death. The cause of ALS is largely unknown, and there are no effective treatments. Researchers recently have used different sources of stem cells to test in rat models of ALS to test for possible nerve cell-restoring properties.
Stroke affects about 750,000 patients per year in the U.S. and is the most common cause of disability in adults. A stroke occurs when blood flow to the brain is disrupted. As a consequence, cells in affected brain regions die from insufficient amounts of oxygen. The treatment of stroke with anti-clotting drugs has dramatically improved the odds of patient recovery. However, in many patients the damage cannot be prevented, and the patient may permanently lose the functions of affected areas of the brain. For these patients, researchers are now considering stem cells as a way to repair the damaged brain regions. This problem is made more challenging because the damage in stroke may be widespread and may affect many cell types and connections.
Similar lines of research are being considered with other disorders such as Huntington’s Disease and certain congenital defects. While much attention has been called to the treatment of Alzheimer’s Disease, it is still not clear if stem cells hold the key to its treatment. But despite the fact that much basic work remains and many fundamental questions are yet to be answered, researchers are hopeful that repair for once-incurable nervous system disorders may be amenable to stem cell based therapies.
