Are we edging towards a cure for Parkinson’s disease? A study in the medical journal Lancet suggests that while we may still be a bit away from a total cure from the disease, there is enough evidence to suggest that it may soon be possible to halt its progression, which is the next step towards managing or eliminating a disease that causes damage to the brain, tremors, difficulty with movements and eventually memory problems.
Parkinson’s disease is caused by the loss of cells which produce the chemical dopamine. The decline to the brain is slow but eventually the accumulated damage causes mental and physical problems. There is no cure for it but current therapies can help to contain the damage and manage the symptoms. They work by boosting dopamine levels, but only manage the symptoms without addressing the damage to the brain.
The Lancet reports that there is evidence now to suggest the progression of Parkinson’s can be delayed. The damage to the brain can be restricted so that no further damage is done. This means that Parkinson’s sufferers retain their mental capacities at the point of diagnosis. This is promising news and the answer lies with a drug normally used in type 2 diabetes.
The trial in the research published in the Lancet was only conducted on 62 patients, so while the evidence is promising and optimistic, further evaluation and studies need to be carried out in order to confirm the findings and the news should be received cautiously. The long-term benefits or side effects are also not completely certain yet. The drug will need more testing; it is easy to be carried away with initial findings but all medication has side effects, either on mental states or physical well-being that we should be mindful of.
The study was conducted by a team from University College London (UCL) team. “There’s absolutely no doubt the most important unmet need in Parkinson’s is a drug to slow down disease progression, it’s unarguable,” Prof Tom Foltynie, one of the researchers, told the BBC.
Currently, there is no drug which achieves that effect. The drugs that are currently prescribed only manage the symptoms, but do not address damage to the brain.
The study divided the 62 patients into two groups. One group received the drug exenatide, which is normally used in the treatment of type 2 diabetes. Another group was given a placebo. Patients were unaware of which treatment they were receiving. For precautionary reasons, all patients also continued to remain on their usual medication.
The 31 patients who received only their usual medication showed symptoms of decline usually associated with Parkinson’s disease. This decline manifested itself both in mental states such as forgetfulness and memory loss, or through the loss of locomotor movement. The results were apparent over a period of 48 weeks.
Patients for whom exenatide was prescribed displayed stability in their results. In other words, their decline due to Parkinson’s was halted. Not only was the further damage to the brain restricted, the loss of physical movement was contained. This suggested that exenatide could have some role in the damage limitation of Parkinson’s disease.
The initial study took place over a year and after that those on exenatide came off the treatment. Yet the benefits of taking the drug continued for up to three months.
Prof Foltynie said, “It gives us confidence exenatide is not just masking symptoms, it’s doing something to the underlying disease.”
Nevertheless, he urged, while we have reason to be encouraged by these positive findings, they still need to be replicated on a larger scale, and the drug also needs to be trialled for a much longer period before any suitable effect and link can be stated.
Another reason to be cautious is that the drug exenatide only made a difference over a maximum trial period of sixty weeks. But in real life Parkinson’s disease afflicts individuals over a prolonged period. The introduction of any new drug into the human body usually causes a noticeable effect at the onset anyway, as the body is flooded by chemicals, but the effect needs to be maintained for prolonged periods without losing consistency. In this particular, case, for a drug to be effective against Parkinson’s disease, it will need to hold back the damage to the brain for years in order that patients who are prescribed the drug would experience a significant improvement on the quality of life.
The effect of Parkinson’s disease is slo. Sufferers experience damage to the brain and slow decline on mind and body over years, sometimes extending up to a decade. The team from University College London said that their research in this 60-week trial produced statistical improvements in quality of life scores, but they will need to extend the benefit over a longer period.
Exenatide’s traditional role as part of a diabetes treatment is in controlling the blood sugar levels in the body. It does this through the action on a hormone sensor known as GLP-1. It is believed that Exenatide makes the hormone sensors work more efficiently or perhaps it improves their ability to survive.
But the GLP-1 sensors are not just found in the body. They are also in existence in brain cells. Those sensors are also present in brain cells too. The current thinking behind using Exenatide in some form as a Parkinson’s disease treatment is that if it can make hormone sensors in the body more efficient, so that they manage blood sugar levels better, then they may have a significant role if used to improve the sensors in brain cells.
It is specifically for this reason that the research of the drug is also being widened beyond its effect on Parkinson’s disease, but also in other neurodegenerative diseases such as Alzheimer’s disease.
David Dexter, the deputy director of research at Parkinson’s UK indicated that there was hope offered through the finding that drugs like exenatide, or perhaps similar ones, could slow the course of Parkinson’s that we currently take for granted. They offer some posibilities that other drugs do not.
“Because Parkinson’s can progress quite gradually, this study was probably too small and short to tell us whether exenatide can halt the progression of the condition, but it’s certainly encouraging and warrants further investigation.”
But amidst all the optimism generated by the possible positive effects on exenatide, Dr Brian Fiske, from the The Michael J Fox Foundation for Parkinson’s Research, cautioned that “the exenatide studies justify continued testing” but that clinicians and patients should not rush to “add exenatide to their regimens” until the impact and safety of exenatide had been proven.
How does Parkinson’s disease gradually lead to the decline of physical movements and memory loss? The disease affects the brain by a slow process of decline and brings on debilitating loss of movement. It has since been discovered that the damage to the brain is also synonymous with accumulation of high levels of the protein alpha-synuclein in the brain.
Scientists at Columbia University Medical Center and the La Jolla Institute for Allergy and Immunology found that T-cells, a part of your immune system, tries to destroy the alpha-synuclein in Parkinson’s disease sufferers, but it is through the killing of alpha-synuclein as an auto-immunity measure that the T-cells inadvertently kills brain cells where the alpha-synuclein accumulates. In other words, a malfunctioning immune system is destroying brain cells, which then have a knock-on impact on the brain’s health and physical functions.
In recent years scientists have made significant progress in their understanding of Parkinson’s disease. One emerging possibility that is gradually gaining ground in that Parkinson’s may have its origins in the gut.
“We imagine that T-cells may first identify alpha-synuclein out in periphery, particularly in the nervous system of gut which is not a problem until the T-cells enter the brain.”
Dr Alessandro Sette, from La Jolla, said: “Our findings raise the possibility that an immunotherapy approach could be used to increase the immune system’s tolerance for alpha-synuclein, which could help to ameliorate or prevent worsening symptoms in Parkinson’s disease patients.”
David Dexter also said that the research lent weight to the idea that “the condition may involve the immune system becoming confused and damaging our own cells.
He stressed however that more needed to be done in order for us to have some understanding about how, in the complicated chain of events that lead or contribute to Parkinson’s, the immune system – or a faulty immune one – played its part in the overall grand scheme of things.
Nevertheless, he added that the new research presented new avenues and opened up new insights into current Parkinson’s treatments. He was optimistic, perhaps cautiously so, that “this presents an exciting new avenue to explore to help develop new treatments that may be able to slow or stop the condition in its tracks.”
Is a medical cure for Parkinson’s disease on the horizon then? Perhaps in fifteen or twenty years’ time, we will look back upon these discoveries – that exenatide halts the decline of the brain by improving the proficiency of GLP-1 hormone sensors in the brain; that Parkinson’s disease originates in the gut; that managing the tolerance for alpha-synuclein by T-cells in the brain prevents them from destroying brain cells which lead to impaired mental and physical function – perhaps in the future we will look upon them as defining moments in the cure of Parkinson’s disease.
So could we expect medical prescriptions for Parkinson’s disease soon? At the earliest, a medical prescription for Parkinson’s will take at least ten to fifteen years to be made available. Pharmaceutical companies are normally granted a patent of twenty years to be the sole distributor of a medical product, in order to reward the impetus and the research undertaken into the product. At least half the amount of time is spent on research and further clinical trials. Most pharmaceutical companies apply for their patent from the time detailed research begins, so that the event that having done a significant part of their research, another company is awarded the patent, is avoided. So the moment a patent is awarded, in this case, for exenatide or a derivative product to tackle Parkinson’s disease – that is a sign we could expect a cure in about ten to fifteen years.