First, what is Parkinson’s Disease?
Parkinson’s disease (PD) is a degenerative disorder of the central nervous system, characterized by the death of dopamine-generating cells in the substantia nigra, leading to neurologic symptoms including tremor, rigidity, slowness of movement and difficulty with walking. Traditionally a clinical diagnosis, uncertain cases can now be more readily confirmed using a DaTscan.
Early PD, showing L>R rest tremor, awkward movement of the L hand, rest tremor walking, and increased tone in the L arm:
More advanced PD, showing stooped posture, rest tremor, slow hesitant gait and difficulty turning, and poor postural reflexes (risk of falls).
How is it usually treated?
Modern treatments are effective at managing the early motor symptoms of the disease, by:
1. Taking extra dopamine, in the form of the precursor drug L-Dopa,
2. Taking MAO-B or COMT inhibitors, which inhibit the breakdown of dopamine, or
3. Taking synthetic dopamine agonist drugs, which bypass dopamine, and bind directly to the dopamine receptors.
Patient with moderately severe PD, fist untreated (left panel), then after taking L-Dopa medication (right panel).
Then what happens?
Unfortunately, as the disease progresses, patients develop motor complications characterized by involuntary movements called dyskinesias and fluctuations in the response to medication. As this occurs, PD patients a can change from phases with good response to medication and few symptoms (“on” state, center panel in video below), to phases with no response to medication and significant motor symptoms (“off” state, left panel in video below), then to dyskinesias (right panel in video below). It becomes harder and harder to keep the patient “on” (middle panel) with medical treatment.
What about surgery for PD?
Deep brain stimulation (DBS) surgery to implant a medical device called a brain pacemaker in to the subthalamanic nucleus or globus pallidus can still be an option for PD patients with significant motor fluctuations, as long as they do not have dementia.
So, we still need more treatment options! What about stem cells?
Current therapies do improve motor symptoms, but they become less effective with time, and do not address the non-motor features of the disease, including dementia, speech and swallowing difficulties, and the gait/balance problems.
In the hope of finding a better treatment, investigators have been trying to replace dopamine deficiency in the brains of PD patients by introducing embryonic stem cell transplants since the 1980s. Some patients improved, but results were very variable, with many patients showing no benefit, and others developing uncontrolled dyskinesias.
One of the problems is that these foreign transplanted cells are attacked by the PD patient’s immune system. There is also a concern that the implanted embryonic stem cells may undergo a transformation in the PD patient’s brain and grow into cancerous tumors.
However, there’s a brand new study about to start at the Scripps Research Institute in La Jolla California: 8 PD patients have undergone removal of small patches of their own skin, which have been turned into a new kind of stem cell that acts like embryonic stem cells, called induced pluripotent stem cells (IPS), and can then be injected back in to the brain. The main advantage of IPS cells over embryonic stem cells is that they are less prone to rejection by the patients’ immune systems, because the transplanted cells come from the individuals themselves.
Ultimately, the hope is that implanted the stem cells will replace the degenerated cells in the patients’ brains, and start producing dopamine in a more physiologic way, treating all of the effects of PD without the side effects of oral medications.
Only time will tell if this IPS treatment is effective, or if we need some other stem cell strategy to treat PD. We do know that a lot of PD patients and their families and friends are waiting with baited breath.
Find out more about the IPS for PD study here.
Find out more about stem cell therapy for PD from the Michael J. Fox Foundation.