Progress for patients with Parkinson’s disease

Health, Pharmaceuticals, Science 2017-04-11

On April 11th this year, World Parkinson’s Day will mark 262 years since James Parkinson was born and 200 years since he published his essay ‘On the Shaking Palsy’, which led to an official recognition of Parkinson’s Disease (PD). Today, it’s estimated that over 10 million people worldwide have PD. Despite widespread awareness of PD and its most common symptoms, scientists don’t know why PD develops, and there is no cure. As a result, treatment has been restricted mostly to drugs that ease the symptoms, and physiotherapy.

Researchers have been exploring PD extensively over the decades and are closer to understanding its underlying biology. These studies are leading to promising new drug treatments that are now entering clinical trials, as well as new possibilities for reversing PD by repairing patients’ brains. Here’s a quick summary of a few recent developments.


What is Parkinson’s?

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PD is a progressive neurodegenerative disease. It causes nerve cells in parts of the brain that control movement to stop working and die off. In healthy brains, these neurons rely on the brain chemical, dopamine, to communicate with one another. Replacing the lost dopamine in PD patients’ brains has therefore been the focus of many treatments over the decades.

Although PD is a degenerative disease that is more common in older people, we now know it is not specifically a disease of old age: around five to ten per cent of PD patients are aged under 50. Currently, there are no biochemical tests for PD; diagnosis depends on observation of the patient by a clinical and/or neurological specialist.

Every patient’s experience of PD can be different, but common symptoms include tremors – especially in hands or fingers when the limbs are at rest, slowness of movement and stiff, rigid muscles. These effects can be painful as well as debilitating, and become progressively worse.


Treating Parkinson’s

It’s a challenging disease to diagnose, predict and treat for several reasons. The speed at which the disease progresses and symptoms develop can vary from one patient to the next. Sometimes Parkinson’s is hereditary, but most of the time it’s not. More recently, scientists have discovered that Parkinson’s can also affect parts of the brain that don’t control movement, resulting in a variety of ‘non-motor’ effects that include mental illness such as depression.

Since the 1960s, PD patients have been prescribed drugs such as levodopa that increase dopamine in the brain. Such drugs help to improve patients’ mobility but are associated with unpleasant side effects that typically get worse over time and can contribute to the patient’s illness. It’s also common for patients on these drugs to experience sudden “off periods” when the treatments just stop working. In the long term, the side effects can seriously outweigh the benefits of the treatment and there is an urgent need for more effective drugs.


Finding new drug treatments

In recent years, scientists have learned more about the biology of Parkinson’s and how it causes nerve cells to malfunction. Researchers have been particularly interested in Lewy bodies, which are clumps of proteins that typically appear in the affected brain cells of PD patients. One of the main components of Lewy bodies is alpha-synuclein, and a number of experiments have shown that alpha-synuclein could play a role in the development of PD. As a result, drug companies are now investigating whether new therapies targeting alpha-synuclein could prevent PD development, or at least slow down the disease progression in patients. Clinical trials have recently started for some of these potential new drugs and the Parkinson’s community is eagerly awaiting the results.


Replacing damaged brain cells

An alternative approach to PD treatment is to transplant new cells into the brain, to replace the dead cells. Several different methods have been tried over the past few decades, including transplants of dopamine-producing foetal cells and, more recently, stem cell grafts. In the late 1980s, researchers at Lund University in Sweden successfully transplanted dopaminergic foetal cells into the brains of 18 patients with Parkinson’s. The majority of the patients showed long-term improvements in their symptoms and some of them were able to stop taking levodopa.

One of the patients from the study died recently, 24 years after the transplant, and post-mortem analysis provided a detailed picture of what happened to the transplant in the patient’s brain. During his life, the patient had initially responded very well to the transplant: he was able to come off levodopa completely for a few years, then continued for ten years on a reduced drug dose. The patient then started to decline and, by 18 years after the transplant, the patient’s disease symptoms were similar to those shown before the study. In line with these behavioural observations, post-mortem analysis of the patient’s brain showed that the transplanted cells had grown into the damaged brain areas and successfully formed new nerve connections (re-innervation). However, signs of Parkinson’s disease, such as Lewy bodies, were found in a small proportion of the transplanted cells.

Further transplant studies have been carried out since the pioneering Lund study, but with mixed success. However, it has been generally accepted that cell replacement could be beneficial for PD, and researchers are now investigating modified approaches using stem cells that can develop into dopamine-producing neurons when transplanted into the brain.

Stem cells have attracted a lot of interest for repairing human brains and other organs in recent years. These immature cells have not yet differentiated into their final cell type (such as skin, muscle or brain cells) and, therefore, have important advantages for brain repair. Importantly, stem cells are much more widely available than foetal tissue because stem cells can come from a variety of sources, including adult humans, and can also be grown in the lab. A special type of inducible stem cell (iPSC) can be manipulated to grow into almost any type of cell that’s specialised for the brain or body region of interest. Scientists are now researching iPSCs as well as other types of stem cell for transplanting into Parkinson’s brains, and it’s expected that these will soon be ready for testing in PD patients.


Tailoring treatments to patients

Another area of research that could be beneficial for PD in the future is personalised medicine. This approach relies on collecting individual patients’ biological information and using that to decide the best course of treatment for the patient. For example, the data might include details about a patient’s immune system, their genes, and levels of hormones and other proteins or biomarkers. This can provide important information about the patient’s stage of disease and response to treatment. In turn, this helps with their prognosis and finding more tailored treatment regimes. Although much work has yet to be done before new Parkinson’s treatments become widely available, the personalised medicine approach could be particularly beneficial for PD given the variation seen in patients’ symptoms, disease progression and response to existing treatments.

What are your thoughts on future treatments for PD? Let me know Kate@Notch


Sources

Lindvall O, Rehncrona S, Brundin P et al. (1989). Arch Neurol 46(6): 615-631.
Lindvall O, Brundin P, Widner H et al. (1990). Science 247(4942): 574-577.
Stoker TB & Barker RA (2016). Regenerative Medicine 11(8): 778-786.
Parkinson’s UK
Parkinson’s Disease Foundation
The Michael J Fox Foundation

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