Are we nearing a medical cure for Parkinson’s disease?

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.

Wort on earth: St John’s wort and its use as an anti-depressant

St John’s wort, also known as Hypericum perforatum, has for years been used as a treatment for nerves. Its use dates back to over hundreds of years. In medieval times, its reputation as a remedy for wounds, as well as sores, burns, bruises and nerve pains, gave it its popularity. Evil spirits were also thought to be repelled by it, and the insane would often drink an infusion of St John’s wort in an attempt to ward off madness. In modern times, St John’s wort has been used to manage seasonal affective disorder (SAD), improve sleep quality and improve mood.

St John’s wort is a tall wild plant and the flowers are yellow. It is often found growing wild in many parts of the world including Europe, Asia and the US, and is named after St John the Baptist as the traditional collection day was on St John’s Day, June 24th.

It is sometimes used by people with mild to moderate depression as an alternative to anti-depressants. It is in this group that scientists believe the best effects of St John’s wort are best demonstrated. We have seen in earlier posts that less severe depression, where sufferers are not in immediate danger, may not require anti-depressants or other medication and if they are not necessary, it is best not to use them as they can lead to addiction or have other side effects.

St John’s wort has been one of the most well-researched herbal medications. While the results of its use are not necessarily consistent, studies have demonstrated that if it is taken in the right form and with the correct dosage, it can have effective results on sufferers with mild to moderate depression. Scientists believe that it works in a similar way to SSRI drugs. SSRI (“selective serotonin re-uptake inhibitor”) drugs lift the levels of certain brain chemicals, such as serotonin, dopamine and noradrenalin, and in doing so make the user feel more positive. Drugs such as Prozac have the same effect. For mild to moderate depression sufferers this sort of herbal treatment is usually enough.

While St John’s wort is available as a traditional medicine, it is classed under “herbal” alternatives which are not necessarily regulated by law. This means that different variants are available, all with different consistencies. If you are considering this as a non-medical alternative, and are slightly puzzled by the variants on offer, it is best to start off with one that has been certified as a Traditional Herbal Remedy, or THR. The symbol for this is a leaf in a black square on the label, and is a useful starting point in guaranteeing the safety and purity of the product.
Effective products will contain a concentration of the active ingredient, hypericin, of about 0.3%. And a good guideline is a product that has a dose of around 300 – 900 mg of hypericin. Start with the median dosage of around 600mg and then adjust it according to how you feel.

It must be emphasised that the usage of St John’s wort has to be considered with the same caution of any prescription SSRI anti-depressants that it is meant to substitute. This means you should use it carefully, and not think that just because it is a natural herbal remedy, taking it – either within the guidelines or above the recommended threshold – will not do you any harm. The use of St John’s wort can cause interference with other drugs and lead to complications. St John’s wort may interfere with statins, blood thinners and also things like oral contraceptives like the pill. Possible side effects could also include nausea, skin allergies and hypersensitivity to sunlight. St John’s wort should also not be taken with drugs prescribed for depression, as that would result in an overdose of hypericin. If you are considering using it as a herbal substitute to reduce mild or moderate depression, it would be a good idea to check with your GP, or consult any other medical practictioner so you have some idea of the associated risks.

St John’s wort, in Germany, is classed as a prescription drug but outside of Germany, it can be readily bought at pharmacists without the need for a prescription. Is it more advantageous to the average person that it is classed as a herbal remedy?

On the face of it, yes – being classed as a herbal remedy means that depression sufferers may try it first before going to their GP. If the remedy works for them, this means that they are more likely to avoid addiction to anti-depressants, and the side effects of the latter. They are also more likely to avoid requiring long-term medication due to the build-up of anti-depressant resistance. Furthermore, users of St John’s wort need not visit their GP to obtain a prescription, so there is a time saving for the GPs and more appointments can be made available.

However, one may argue that its listing as an alternative health herbal remedy only complicates matters. St John’s wort is found in the form of tablets, teas and tincture. Herbal remedies, like vitamins, cannot make the claim that they can cure a certain illness, but manufacturers can claim they are good for certain purposes. Therefore, St John’s wort can be said to “be good for mild depression”, but not cure it. But this is not the only disclaimer found in the text in St John’s wort products. In trying to absolve itself of litigious claims, it is not uncommon to see on the labelling that St John’s wort should not be taken if:

  • you are under 18 years of age
  • you are pregnant or breastfeeding
  • you are allergic to any of the ingredients
  • you are lactose intolerant
  • your skin is exceptionally sensitive to sunlight (photosensitive)
  • you are having light treatment (phototherapy) for any condition
  • you are suffering from depression

The printed label may also advise you that it may also interfere with medicines such as:

  • fentanyl, propofol, sevoflurane, and midazolam (anaesthetics/pre-operative medicines)
  • tramadol (an analgesic)
  • erythromycin, clarithromycin and telithromycin (antibiotics)
  • itraconazole and voriconazole (antifungals)
  • artemether and lumefantrine (antimalarials)
  • rasagiline (an anti-Parkinson’s medicine)
  • aripiprazole (an antipsychotic medicine)
  • buspirone (an anxiolytic)
  • aprepitant (used to treat post-operative vomiting)
  • butobarbital and phenobarbital (barbiturates)
  • methyl phenidate (a central nervous system or CNS stimulant)
  • exemestane (a hormone antagonist)
  • eplerenone (a diuretic)
  • lansoprazole and omeprazole (proton pump inhibitors)
  • theophylline (a bronchodilator)
  • gliclazide (an antidiabetic medicine)

A longer, more detailed list may advise that St John’s wort should not be used for:

  • All medicines for depression/anxiety – Amitriptyline, clomipramine, moclobemide, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine
  • All hormonal replacement therapy treatments – HRT tablets, patches and gels
  • All medicines for thinning the blood (anticoagulants) – Warfarin, acenocoumarol
  • All medicines for epilepsy – Carbamazepine, phenobarbitone, phenytoin, primidone, sodium valproate
  • All immunosuppressant medicines – Ciclosporin, tacrolimus
  • All medicines for HIV infections – Amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir, efavirenz, nevirapine, delavirdine
  • Cholesterol medicines such as Simvastatin, atorvastatin
  • Cancer medicines such as Irinotecan, dasatinib, erlotinib, imatinib, sorafenib, sunitinib, etoposide, mitotane
  • Heart disease medicines- Digoxin, ivabradine, amiodarone
  • Migraine treatments – Almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan
  • High blood pressure treatments – Amlodipine, nifedipine, felodipine, verapamil
  • A medicine for regulating mood – Lithium
  • A thyroid hormone – Thyroxine

The list of precautions and possible medication conflict is so long, that one may find sufferers who are actually already on medication may decide against switching or downgrading to St John’s wort.

The dosing and safety of St John’s Wort has – in addition – not been studied in children/ adolescents below 18 years and hence the safety of use is not established.

Where Will factors in mental health treatment

If medication is a physical stabiliser, is therapy a mental stabiliser?

If you’ve read the last few posts you might have come to the conclusion that as far as mental health is concerned, the line of thinking contained in this blog is that an approach that is suitable for long-term and lasting treatment is part medication and part therapy. Medication initially works best for more serious cases, and milder forms of mental health illnesses may be possible without the use of prescription medication, but for the long term, it is better to wean patients off the medication. Not simply because the use of medication over longer periods breeds addiction, dependency and causes changes to the body which may be harmful, but for the health service, it is an unsustainable form of treatment that simply continues to deplete the environment of its resouces while contributing to climate change and extreme weather. It seem strange to have to mention climate change in a medical blog, but essentially this is what we can trace it back to.

Medicine, especially for serious cases of mental health, is an effect-suppressant that minimises immediate symptoms while buying time for alternative therapies that promote long-term solutions to kick in. But there are those who consider if medication if even neccesary at all. After all, the body does a pretty good job of healing itself when we get cuts. Those who ascribe to this view hold that given time, the body does what it needs to prepare itself for survival and growth.

The only problem that time is not always an available resource. Sometimes we need results in a short space of time, and do not have the luxury of seeing the effects of mental illness dwindle away over years. Medication provides a higher level of immediacy to treatment. To some, it seems that medication is flooding the body with chemicals it could obtain or manufacture from within, but within a shorter span of time and with a higher concentration. It is giving the body what it needs in an intensive period rather than over a longer span of time that the non-medical proponents advocate.

Some go further to suggest this no-medication approach can be extended to the therapy aspect of mental health treatment. They argue that therapy, counselling or any other cognitive methods of treatment only serve to increase stresses rather than decrease them. While no one would ever advocate a completely non-medicated and non-therapy treament for mental health illnesses, and the current thinking is a part-medical and part-therapy approach to mental health illnesses, there are those who might consider a non-medicated but supported therapy approach. Another variant of this is the medicated but no therapy group. It is this last group which we will consider further.

On the face of it, it seems preposterous to even suggest it. If we have believed that mental health illnesses can only be treated in the long term with therapies such as counselling, then how is it even possible to consider a zero-therapy treatment group?

Proponents of the above idea hold that the therapy causes stress rather than deals with it on a long term basis. What patients really need, it is argued, is mental space to dwell on their lives, reflect on how they are living, then in order to make long-term changes, they have to find solutions within themselves and the will to apply them. Methods such as counselling and cognitive therapy already exist, but as the solutions are arrived at through the meetings within the counsellor and patient, it is felt that certain patients may only view the changes they have to make as being dispensed by the counsellor, and see them as extrinsic factors. Hence the guidance may be less effective. However, if they are given time and space to reflect on what they need to do, having examined their situation in detail for themselves, it is one that they will be more effective in finding the will to put actions into practice.

Take for example, the caterpillar. Cocooned in security, it makes minute adjustments day by day to prepare itself for the life ahead. To the outsider it looks as if nothing is going on, but this could not be further from the truth. As it is about to break out and emerge as a butterfly, it has to struggles and somehow bridge the gap from where it is, to where it must be. The final trials, as it tries to break out from the cocoon actually help to strengthen and develop its wings permanently. Maturity is arrived at without any extrinsic factors. The caterpillar made it on its own. If someone had helped it, perhaps by thinking to widen the gap through which it must emerge, the lack of pressure and resistance would actually cause the emerging butterfly to have weaker wings and have a poorer chance for long-term survival.

Those that point to a no-therapy solution claim that the guidance of the counsellor, psychotherapist or assisting care individual actually puts a timeframe on what could actually be a non-hurried adaptive process of the mental health patient. A counsellor is paid, either through the mental health patient directly or from a health service. The presence of a counsellor may only impose a time-limit by which progress must be made because health care funds will run out, or perhaps accountability demands that the patient make progress at a speed that may not be concordant with the natural run of things. The pressure to be at a certain mental stage in time may only impose an additional counter-productive burden in the first place.

A common factor in depression is the dwelling on the gulf that exists between where one is and where one wants to be. The prolonged over-emphasis on the disconnect between both disparate worlds is one of the reasons why individuals develop unhappiness and long-term depression. Yet the argument could be made that counselling and cognitive therapy, while aiming to bridge that gap, may not be effective in helping patients develop the skills and will to bridge the gulf in order to take their development forward. Often the development has to follow the patient’s natural timing and pace, and if this important counselling cornerstone is disturbed, then the advice and guidance received from the counsellor will merely be more pieces of information dropping into the gulf and  widening it further.

Some point to a period of reflective solitude as the necessary key to a long term solution. The individual goes at a pace he is suited to, slowly adapting to the needs of his situation and developing the skills for long term recovery. A self-monitoring form of silence and meditation is imposed. The theory behind this thinking could not be any more different from traditional approaches. Where traditionally some form of intervention might be applied to, say, an individual lying in bed and unable to face the day ahead, either through the dispensing of advice such as “Man up! Toughen up!” or visits to therapists, proponents of the reflective solitude theory view the process as the individual resting himself in preparation for the changes ahead, akin to the caterpillar. The belief is that the mere thought of an activity triggers physical processes in the motor nerves, so by resting, the individual is clearing his mind and soul and preparing his body before he can fill it with more useful purpose. It is not a major problem that the resting may  take place over a period of weeks. But the belief is that ultimately the individually will feel compelled to make some changes to better his situation, and the will to do so will have been found.

To take the argument further, and possibly to an extreme, does therapy perform only the role of a distractor or mental substitute? While medication performs the function of a physical stabiliser, does therapy perform the role of a mental stabiliser, stabilising the mood swings and thoughts of the affected individual, before Will, binding these altogether, prompts the individual to leap across the gulf between “where I am” and “where I want to be”?

If you believe that real, long-lasting change can only come about when the mind and body are relatively stable, and given time, an individual posseses the inherent power to heal themselves of mental illness and free themselves from the shackles of the likes of depression, then you might make the case that therapy isn’t as important as it is cut out to be. Is therapy really necessary in this case, and can it be replaced by recreational interests, for example, where parts of the brain that are latent come to the fore, and override the parts of the brain that trigger mental illness?

It would be simplistic to find a direct link between mental health and recreational interests or hobbies. Hobbies do not directly cure mental illnesses. But what they can possibly give is a sense of achievement and empowerment to an individual, subtly developing the mindset and will that change can be attained. The subtle aspect of development is an important one, it is an indirect way of going about developing achievement and staying hidden until the affected individual one day surmises his development and can see measurable progress that could spur him on to make great strides in matters of more concern. If, for example, a mental health sufferer takes up a hobby, such as learning a musical instrument like the piano, the time and energy invested into this may draw excess energy and time away from that invested into unnecessary mental worry, resulting in a greater sense of overall well-being.