The Potential of Neuronal Transplantation in Treating Parkinson’s Disease
Parkinson’s disease (PD) is a neurodegenerative disorder that primarily affects a person’s movement. While the symptoms appear gradually, they eventually get worse over time. People who are in the advanced stages of the disease have difficulty walking and talking, experience loss of balance, have slower reflexes, and exhibit mental and behavioral changes. They may also come to a point where they can no longer stand or walk without assistance.
Parkinson’s disease is an extremely debilitating condition affecting approximately one percent of the U.S. population over the age of 60 and more than 10 million people around the world. And although some cases appear to be hereditary or can be traced back to specific genetic mutations, the majority of cases seem to occur at random.
Until now, there is still no known test for diagnosing the disease and no known cure, either. The prognosis had been bleak until neuronal transplantation started showing some very promising results.
Neuronal Transplantation as an Alternative Treatment for Parkinson’s Disease
Parkinson’s disease occurs when the dopaminergic neurons in the area of the brain responsible for controlling movement die or become impaired. While scientists are not sure why these dopamine-producing cells die, several alternative neurosurgical therapies, including neuronal transplantation, have been developed and tested to treat or manage the disabling symptoms of the disease.
Unlike other neurosurgical procedures, cell transplantation does not leave destructive lesions within the basal ganglia nuclei. Instead, it rebuilds the normal nigrostriatal pathway by replacing lost or dysfunctional neurons in the hope of restoring its ability to produce dopamine (DA).
Cell replacement as a treatment for PD holds tremendous potential due to several reasons:
- The most significant neuronal degradation is not only site-specific but also type-specific (i.e., dopaminergic).
- The target area (the striatum) is well-defined.
- Postsynaptic receptors are intact.
- The neurons that stimulate the receptors are capable of performing a modulatory function.
Some of the earliest cell replacement therapy trials (which were conducted in the late 1980s) reportedly used neuronal grafts from the brains of aborted fetuses. Although the trials reportedly yielded long-term benefits for some PD patients (some were able to come off their anti-PD medications for years), some patients exhibited minimal to no clinical improvements, while other patients experienced graft-induced dyskinesia (GIDs) as a result of the experiment.
Some physicians also found the procedure to be highly unethical.
Taking these factors into account, alternative donor cell grafts (including stem cells, xenografts, genetically engineered cells, immortalized cell lines, and paraneural cells) were examined to address the logistical and ethical issues involved in using human fetal cells.
In 2009, cell biologist Kwang-Soo Kim published a paper on how induced pluripotent stem cells (iPS cells) can be generated from adult fibroblasts. The beauty of these cells lies in their ability to turn into any of the specialized cells (e.g., muscle, liver, heart, brain, etc.) in the human body under the right conditions.
Earlier, Shinya Yamanaka, a Japanese stem cell researcher, discovered that mature cells can be reprogrammed to be pluripotent (can develop into all cell types), earning him the 2012 Nobel Prize for Physiology or Medicine. In Yamanaka’s original iPS research, he and his team identified four transcriptional factors (Myc, Oct3/4, Sox2, and Klf4) that can efficiently convert fibroblasts into pluripotent stem cells.
While Yamanaka’s research has several limitations (i.e., low production rate of iPS cells and the oncogenic nature of the identified transcriptional factors), it proved that intact differentiated somatic cells can be effectively reprogrammed to become pluripotent.
To date, further improvements were made to the technology. These include the replacement of the retroviral factors in the delivery mechanism with non-integrating viruses, stabilized RNAs, or episomal plasmids and the identification of transcription factors necessary for inducing pluripotency in different cell types.
Yamanaka’s discovery also proved that lost or dysfunctional cells can be successfully replaced without the risk of being rejected by the host’s immune system, making cell replacement therapy a likely candidate in treating Parkinson’s disease and other degenerative diseases.
