Isthe drug Levodopa the best option to fight Parkinson's disease?

Table 1: Classification of disability

It’s important to treat Parkinson’s as soon as possible before the conditions become worse. However, in the early stages where the disease is mild, symptoms recorded can be similar to other diseases such as Parkinsonism. Doctors will find it hard to say that a patient has Parkinson’s Disease until the later stages where symptoms are more severe.

The problem

The main problem is that this disease is on the rise. In 2005 there was an estimated 4.1 million people having parkinson’s disease and this figure is expected to rise to more than double that figure by 2030. It increased by 4.6% from 2009 -2010 which was the greatest increase for the cause of deaths as stated by the CDC (US centre for disease control). In the US the death rate for Parkinson’s disease has more than tripled as shown below. This is because the more developed a country is the better it’s health service and therefore the older their average population is. Since this affects the older generation, as shown by the bar chart below, an ageing population means that more people are living longer and therefore there is a greater population vulnerable to this disease. This has a knock on effect to the economy with $27 billion lost in medical bills and salary.

Both rates are per 100,000

This disease however is idiopathic meaning that there are no known causes which makes it very hard to combat. With no current cure to this disease, scientists are trying to find new methods to provide relief for the symptoms caused by this, one of which is the use of levodopa.

The main solution

At the moment scientist use the drug levodopa (L-DOPA) to combat Parkinson’s disease and has been commonly used as treatment over the last 30 years. L-DOPA works by being converted to dopamine to replace those the lack of them through the death of the generating cells. It is able to do this because it is able to cross the blood-brain barrier where dopamine cannot and therefore can increase the dopamine levels. Once the L-DOPA enters the central nervous system it gets converted into dopamine by enzymes.

However, there are implications to using this method. One of which is that only 5-10% of the L-DOPA is converted in the central nervous system as the rest is converted in the peripheral nervous system which causes most of the visible symptoms including nausea. In order to pass these effects the procedure of administration includes to co administer other drugs such as a peripheral DOPA decarboxylase inhibitor (DDCI). Examples include carbidopa and benserazide which inhibit the breakdown of L-DOPA in the peripheral nervous system by inhibiting the decarboxylation, therefore there is more L-DOPA available to cross into the central nervous system. They prevent levodopa from being converted to dopamine in the bloodstream. Scientists have also noticed that this combination may also cure other syndromes such as the restless leg syndrome.

There are also other side effects caused by L-DOPA. The most common side effects include hallucinations and vivid dreams as well as anorexia and increased risk of impulse control disorders. The combination of L-DOPA and the DDCI drugs mentioned earlier have side effects that could threaten a person’s life and therefore should not be given to patients who are pregnant, have psychotic disorders or are hypersensitive. There are several precautions as to not make the side effects even worse. One of these precautions is to avoid abrupt withdrawal. Patients with cardiovascular or respiratory disease should also be treated with caution when administering the combination. If taken in low doses there is a general trend showing that it leaves people unaffected. You can then build up the aount of each dose. If you take too much side effects may occur. Over time levodopa loses its effectiveness as most people start taking levodopa develop problems with 40% of people treated with levodopa developing motor fluctuations within 6 years of treatment. However, the overall effect of this drug shows that it is reducing the number of Parkinson’s related deaths. Scientists have conducted several studies into dopamine responsiveness to levodopa and the results state that levodopa does in fact increase the level of dopamine. In a study 22 newly diagnosed patients were took part in the study. 77% of them responded positively with the rest having no effect. This showed that levodopa was successful for raising dopamine levels in the central nervous system.

An economic issue of this method of treating Parkinson’s disease is that the cost of this is very large and exceeds any health insurance and therefore is going to be very expensive for families to provide treatment. The treatment also continues for long periods of time which means that families are likely to not be able to afford all of the treatment. This is also a social issue as richer families will be able to pay whereas loners may die due to not being able to pay for treatment. Since Parkinson’s disease is a long term disease there is a high amount in lost salaries through patients being unable to work as well as lost productivity.

There are several benefits and risks of using this method. One benefit is that L-DOPA is that it is the most effective drug at relieving symptoms such as tremors and slowness for a longer period of time than other methods so it maintains a good quality of life for longer. This is shown below where L-DOPA is compared to drugs that can be used for the treatment of Parkinson’s disease. Since it has the best symptom control it is the most desired drug for this use. Another benefit of using this is that it has a long safe history record so you know that it is safe to use. As well as this L-DOPA is available in large quantities and therefore can provide treatment to lots of people.

Table 2: shows L-DOPA in comparison to other drugs that may be used.

However, there are several risks with using this drug. The risk of this drug is that being administered with it may cause long term effects. One effect is that there may be a developed motor problem 5-10 years into the future. These effects can be just serious as those that the drug tried to relieve. Compared to the other drugs which reduce motor complications L-DOPA doesn’t seem like the best drug. Another risk not mentioned on the table is the fact that using L-DOPA may result in an increased risk of patients developing a skin cancer.

Alternative solutions

Another method that scientists are looking at is cell replacement therapy.  Researchers have been able to transplant developing dopamine-generating cells into animals at first and then human trials. The result was a major improvement in most cases and those who didn’t experience major improvements had slight improvements.  This method worked by specialised cells being inserted into the area with damaged cells. These cells could either be Embryonic cells or Induced pluripotent cells. Since stem cells have been discovered they have opened new doors into the curing of diseases such as leukemia and Sickle cell disease. Scientists believe that stem cells can also answer the problems to curing Parkinson’s disease. Since they know that the disease targets and destroys dopamine-generating cells they believe that creating new stem cells to replace those lost is the way forward. The stem cells then replace the damaged areas and facilitate improved function of the Dopamine- generating cells. These new cells then increase the levels of dopamine generated and therefore provide enough neurotransmitters for quicker movement. If induced pluripotent cells are used an adults skin cells will be taken and used to make dopamine producing cells. However, this method isn’t fully tested and more research is needed to be done. They believe that using stem cells will work due to cell replacement therapy research in the late 20th century. In an study 75 patients underwent parkinsons treatment using stem cells with 36 of the patients reporting significant improvements in their condition and 27 reporting that their condition had slowed and wasn’t getting worse. The graph on the left shows this. However, using these methods causes some ethical concerns about the duty to respect all human life yet we have a duty to prevent suffering. By using embryonic stem cells we aren’t showing respect to the life of the embryo but by doing so we are trying to prevent suffering of others.

Another solution is to perform surgery on patients that have this disease. Performing surgery was very popular before L-DOPA was introduced. Now it is only used on patients that have had Parkinson’s disease for a long period of time.  There are 2 main types of surgery that can be performed. The first is deep brain stimulation which involves implanting leads into 3 points in the patients brain which is connected to a neurotransmitter based under the skin around the chest which can be rechargeable or non rechargeable. After this surgery patients are usually expected to make a full recovery and be able to do activities as before. The other surgery that can be used is lesioning techniques. This involves causing selective damage by inserting an electrode into the target before releasing a small current to damage the cells nearby that control movement. This will therefore reduce the effects of movement symptoms. This is very effective against Parkinson’s disease but it isn’t highly recommended because of the high risk that it will cause irreversible damage.  This method has a 95% success rate which is extremely high showing that this is a very good method to use.

Conclusion

In conclusion i believe that using L-DOPA is the best short term answer to provide relief from the symptoms and hopefully provide an answer to Parkinson’s disease. However, for cases who are lasting longer i think that stem cells would be the best way to deal with it. This is because it is a simple procedure and there is less risk compared to surgery which can cause negative irreversible damage to the cells that control movement.

Bibliography

1. “Parkinson’s disease: how could stem cells help?”  -accessed 1/2/15
2. “Stem cell research”           - accessed 1/2/15
3. “National vital statistics report”  - accessed 2/2/15
4. Clinical Medicine -Eighth edition by Kumar & Clark (Parveen Kumar & Michael Clark)
5. Oxford handbook of clinical medicine- Eighth edition by Murray Longmore, Ian Wilkinson, Edward Davidson, Alexander Foulkes, Ahmed Mafi
6. “Surgery”                                             - accessed 2/2/15

7. “Parkinson's disease: Diagnosis and management in primary and secondary care”  - accessed 5/2/15

8. “Parkinson’s Disease”  - accessed 7/2/15
9. “Parkinson’s Disease”                 - Accessed 7/12/15
10. “Parkinson’s Disease Medications”
11. “The levodopa test in Parkinson's disease”

Validity of the sources

Sources 4 and 5 are quite reliable on the background of parkinson's disease and how L-DOPA can be used to fight it. This is because the information on how L-DOPA raises dopamine levels in the oxford handbook of clinical medicine corresponds with that in the clinical medicine textbook.