Novel Breakthroughs in Parkinson’s Disease Treatmentby Viatcheslav Wlassoff, PhD | July 29, 2015
Around 7 million people around the world are diagnosed with Parkinson’s disease every year. This is a progressively degenerative disease that has no cure. There have been, however, a number of very encouraging findings published in the last few weeks, some of which are briefly reviewed in this article.
Drugs to manage the symptoms of Parkinson’s disease are available, but they become ineffective after the patient has taken them for a few years. Deep brain stimulation (DBS) is a surgical procedure for patients in the advanced stages of the disease. It involves implanting electrodes in the movement regions of the brain. The electrodes are connected to a pulse generator that is placed under the collarbone and sends electrical signals to the brain. This method can manage symptoms of the disease which include slowness of movement, stiffness, and tremors. But it is expensive, not everyone is deemed fit to go through this 10-15 hour invasive surgical procedure, and the method is believed to trigger cognitive and mood disorders.
The quest was always on to find non-invasive ways to manage the symptoms of Parkinson’s disease. Now there seems to be light at the end of the tunnel. Scientists have discovered that certain drugs and a headband that delivers electrical signals can be used to manage the symptoms of Parkinson’s disease.
Non-invasive brain stimulation
Students at Johns Hopkins University have suggested using a non-invasive therapy called transcranial direct current stimulation (tDCS). In this method, a headband-type device with two electrodes — a cathode and an anode — is fitted over the head of the patient to deliver low-intensity current to specific motor areas of the brain. The current stimulates (under the anode) and inhibits (under the cathode) neurons that, in turn, may control the symptoms of the disease. The device has not yet been tested on humans, but the idea is promising because it is based on sound logic backed by science.
Cortical dysfunctionality has been implicated in Parkinson’s disease. Neuroimaging and neurophysiologic studies have shown that hyper- or hypo-stimulation of certain areas in the brain, like the motor cortices, may trigger symptoms of the disease.
Scientists had recognized the efficacy and safety of non-invasive neuromodulation procedures like tDCS as alternatives to the DBS method quite some time ago. The application of this procedure on subjects with Parkinson’s disease during clinical trials has led to symptomatic relief for short durations, just a few minutes. There were no adverse reactions because the electrodes were placed precisely over those cortical regions that are involved with movement. There were also no unintended outcomes across multiple cortices that are associated with other symptoms.
Scientists believe that stimulating the motor and prefrontal cortices may relieve some symptoms of the disease. Later studies also confirmed that tDCS can improve hand motor functionality in stroke patients. However, all the studies confirm that the primary challenge is to make the benefits of tDCS last longer. The scientists think that repetitive sessions of tDCS using higher-intensity currents can prolong cortical excitability. The stimulation parameters — the strength of the current, the number to be applied per session, the number of sessions and the interval between them, and the specific areas of the brain to be targeted — have to be nailed down precisely to replicate positive results and make predictions. Investigations are underway.
Anti-malarial drugs to fight Parkinson’s disease
The gold standard of current treatment for Parkinson’s disease is dopamine replacement therapy. But this treatment method has its drawbacks, the greatest being that it cannot stop the progress of the disease or reverse the symptoms. The only way around this flaw was to find a non-dopaminergic drug.
According to a study published few weeks ago, existing anti-malarial drugs can be made to improve the symptoms and stop the progress of the disease in laboratory rats. Nurr1 is a group of proteins that can preserve the brain’s capacity to produce dopamine, protect the existing ones from death by inflammation, and enhance their functionality. Scientists engaged in this study have discovered that anti-malarial drugs like Amodiaquine and Chloroquine can activate Nurr1 and promote its functions.
A critical deficiency of the current dopamine replacement therapy is that after a few years of administering it, patients report serious side effects like dyskinesia. In the Nurr1 study, it was found that the symptoms of the rats improved and the progression of the disease was halted without the animals exhibiting dyskinesia behaviors.
Other pharmacological approaches to treat and manage Parkinson’s disease
Another recent study suggests that a novel pharmacological approach can prevent neurodegeneration associated with Parkinson’s disease.
It has been found that degeneration of dopamine neurons in the substantia nigra region of the brain and an abnormal deposition of the alpha-synuclein protein in the other neurons from years before the manifestation of the disease are the classic features of Parkinson’s disease. Scientists also know that a specific mutation of the LRRK2 enzyme is present in about two percent of all Parkinson’s patients and that laboratory rats without this enzyme are protected from neurodegeneration even though they had an excess of alpha-synuclein.
The above-mentioned experiment was conducted on laboratory rats that had the exact mutation of the LRRK2 enzyme that is known to trigger Parkinson’s disease and an excess of ?-synuclein. Scientists discovered a class of LRRK2 inhibitors that when fed to the rats halted neurodegeneration.
Other researchers are experimenting with ways to combine pharmacological approaches to increase the effectiveness and sustainability of dopamine replacement therapy.
Several years ago it was shown that movements in Parkinson’s patients can be improved by stimulating dopaminergic receptors and inhibiting adenosine A2A receptors together. Researchers believe that adenosine A2A inhibitors should be used together with dopamine-stimulating treatments. In laboratory tests, the administration of adenosine A2A inhibitors not only improved mobility in the patients but also did not trigger the side effects that are usually associated with the L-DOPA therapy, the standard medicine used to raise dopamine levels in patients. What is more, researchers think that using adenosine A2A inhibitors will also let doctors reduce L–DOPA dosage and thus prevent the onset of side effects like severe fluctuation in dyskinase behavior that are typically associated with the drug.
A later study identified three adenosine A2A inhibitors—BIIB014, preladenant, and ST-1535—that can be used in conjunction with L-DOPA to improve the latter’s efficacy in late stages of the disease. This study also found that BIIB014 is effective on its own during the preliminary stages of the disease.
The above-mentioned breakthroughs in the treatment of Parkinson’s disease gives hope to millions. Patients suffering from other movement disorders like dystonia can also hope for a cure that will let them lead productive and meaningful lives.
Benninger, D., Lomarev, M., Lopez, G., Wassermann, E., Li, X., Considine, E., & Hallett, M. (2010). Transcranial direct current stimulation for the treatment of Parkinson’s disease Journal of Neurology, Neurosurgery & Psychiatry, 81 (10), 1105-1111 DOI: 10.1136/jnnp.2009.202556
Cie?lak, M., Komoszy?ski, M., & Wojtczak, A. (2008). Adenosine A2A receptors in Parkinson’s disease treatment Purinergic Signalling, 4 (4), 305-312 DOI: 10.1007/s11302-008-9100-8
Daher, J., Abdelmotilib, H., Hu, X., Volpicelli-Daley, L., Moehle, M., Fraser, K., Needle, E., Chen, Y., Steyn, S., Galatsis, P., Hirst, W., & West, A. (2015). LRRK2 Pharmacological Inhibition Abates ?-Synuclein Induced Neurodegeneration Journal of Biological Chemistry DOI: 10.1074/jbc.M115.660001
Grefkes, C., & Fink, G. (2012). Disruption of motor network connectivity post-stroke and its noninvasive neuromodulation Current Opinion in Neurology, 25 (6), 670-675 DOI: 10.1097/WCO.0b013e3283598473
Kim, C., Han, B., Moon, J., Kim, D., Shin, J., Rajan, S., Nguyen, Q., Sohn, M., Kim, W., Han, M., Jeong, I., Kim, K., Lee, E., Tu, Y., Naffin-Olivos, J., Park, C., Ringe, D., Yoon, H., Petsko, G., & Kim, K. (2015). Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease Proceedings of the National Academy of Sciences, 112 (28), 8756-8761 DOI: 10.1073/pnas.1509742112
Lefaucheur JP (2006). Repetitive transcranial magnetic stimulation (rTMS): insights into the treatment of Parkinson’s disease by cortical stimulation. Neurophysiologie clinique = Clinical neurophysiology, 36 (3), 125-33 PMID: 17046607
Pinna, A. (2009). Novel investigational adenosine A receptor antagonists for Parkinson’s diseaseExpert Opinion on Investigational Drugs, 18 (11), 1619-1631 DOI: 10.1517/13543780903241615
Wu, A., Fregni, F., Simon, D., Deblieck, C., & Pascual-Leone, A. (2008). Noninvasive brain stimulation for Parkinson’s disease and dystonia Neurotherapeutics, 5 (2), 345-361 DOI: 10.1016/j.nurt.2008.02.002
No future articles scheduled.
This Sunday February 14th (9 p.m. ET), the Emmy-nominated Brain Games tv-show is back! Wonder junkie Jason Silva returns to our screens, teaming up with... READ MORE →
Like what you read? Give to Brain Blogger sponsored by GNIF with a tax-deductible donation.Make A Donation