PARKINSON’S DISEASE


“Deep brain stimulation (DBS) is an intensive


treatment in which


electrodes are implanted into


certain areas of the brain”


has been happening in medicine for decades. Drug repurposing - as it’s known - means that some drugs could be used for PD and/or in conjunction with PD medication.


One example that is already used in PD is apomorphine, a fast-acting dopamine agonist that is generally used in the later stages of the condition. In the 1870s, however, apomorphine was used in small doses for the treatment of alcoholism as it helped to reduce alcoholic cravings. It was not until 100 years later, in the 1970s, that it began to be used for Parkinson’s.


Diabetes drugs One of the most successful drug areas for repurposing so far has been diabetes; especially drugs that target a particular receptor called glucagon- like peptide 1 (GLP-1).


documented, but DBs has also shown promising effects on non-motor symptoms, such as anxiety and depression. Additionally, there is also evidence that DBs can improve sleep quality, musculoskeletal pain and urinary symptoms.


Focused ultrasound subthalamotomy Prior to the development of DBs, movement disorders were often treated with ablative neurosurgery, which involves the removal of a specific brain area. DBs is preferred over ablative neurosurgery due to its reversibility and documented efficacy for PD treatment.


Now, a new technique is available for ablating specific brain areas. Gamma- knife and MRI-guided focused ultrasound (MRgFus) allow for deep brain ablating without having to open the skull. A pilot study using focused ultrasound subthalatomy in patients with PD showed that it was effective, well tolerated and the adverse events seemed to be mostly mild and transient. This new technique provides hope for patients, who don’t want to have their brain opened.


Repurposed drugs using drugs designed to treat one condition for another unrelated one


GLP-1 is a hormone that is produced when someone eats or drinks. It triggers the release of insulin, which helps us absorb glucose from the blood, and so drugs that mimic the effects of GLP-1 are very important for helping people with type 2 diabetes to manage their blood-sugar levels.


Research has shown, however, that receptors which recognise and respond to GLP-1 are also present in the brain, and stimulating these receptors can have positive effects on a host of important functions that help to keep brain cells healthy and working well.


studies on laboratory animals have suggested that drugs that target GLP- 1 receptors could have neuroprotective effects in PD, meaning that they could have the power to slow the relentless damage to dopamine-producing brain cells, and could therefore delay the deterioration of symptoms.


Among the most promising diabetes drugs that have been repurposed are:


Exenatide exenatide has already been tested in two clinical trials, both carried out by researchers at university College London. Results have shown promise that the treatment may help to slow the progression of PD, but have not been sufficiently conclusive. Further, more powerful studies are now being planned that aim to provide a fuller


understanding of the effects of exenatide for people with Parkinson’s.


Lixisenatide and liraglutide Liraglutide and lixisenatide are newer diabetes drugs that also act on GLP-1 receptors, but are longer acting than exenatide. studies carried out in mice treated with a chemical that attacks dopamine-producing brain cells suggests that these newer drugs are better able to prevent damage than exenatide.


There is currently a phase 2 clinical trial of liraglutide for PD underway at Cedars-sinai Medical Center in the states and a phase 2 clinical trial of lixisenatide underway in France. The French trial latter is set to be the largest study of a diabetes drug for Parkinson’s to be conducted to date, involving 158 people.


Diabetes drugs aren’t the only ones to be repurposed for PD, however….


Statins statins are a type of drug commonly used to decrease ‘bad’ cholesterol levels in the blood. Often prescribed to people at risk of cardiovascular disease, statins improve the blood flow and restore the elasticity of the arteries. Lab studies in cells and animal models of PD have suggested that, in addition to their cholesterol- lowering properties, statins may also have a range of activities which could help protect brain cells in PD. These include: • reducing inflammation • reducing oxidative stress • reducing the formation of sticky bundles of alpha-synuclein


• increasing the production of neurotrophic factors


In addition, large scale studies in people have suggested that statins may help to reduce risk of developing PD.


As a result, there is now a clinical trial involving 235 people with moderate PD in 23 hospitals across the uK. The two-year trial features the statin simvastatin, which was selected because it is better able to enter the brain than most other statins.


A liver drug: UDCA ursodeoxycholic acid, which is also known as ursodiol or uDCA, is an old drug that’s used to treat liver disease and to reduce the formation of gall stones.


Researchers at the university of sheffield have discovered, however, that uDCA may have another potential function. When uDCA was tested on skin cells from people with PD, the researchers found that the drug had restorative effects on mitochondria - the tiny, energy- producing batteries that power all of the body’s cells; thereby helping to boost energy production.


The team is now preparing to begin a small clinical trial of uDCA in people with PD to assess safety and look for signs that the drug can have the same effects on mitochondria in people.


A cancer drug: nilotinib Nilotinib is a treatment for chronic myelogenous leukemia (CML). In CML, a mutation causes a protein called Abl to join with another protein called Bcr. The hybrid protein (Bcr- Abl) stimulates the excessive production of white blood cells, leading to many and varied problems. Nilotinib finds and binds to Bcr-Abl, switching it off and stopping white blood cell production.


Recent studies have suggested that a closely-related protein called c-Abl may play a role in the accumulation of toxic alpha-synuclein, and impair the cell’s ability to process and remove waste - both problems, which are thought to contribute to the loss of brain cells. Drugs that can find and bind c-Abl (like nilotinib) may therefore help to protect struggling brain cells and have the potential to slow Parkinson’s.


An iron-removal drug: deferiprone Iron is essential to the body, but too much can be toxic and can contribute to damaging processes like oxidative stress. Deferiprone is a drug that is already used by people with blood disorders to help them remove excess iron, and it is able to get into the brain.


Two small clinical trials in France and London showed such encouraging findings that a major european union-funded clinical trial featuring more than 3000 people across eight european countries was established. Researchers are hoping to show that treatment with deferiprone can slow the progression of PD in comparison with placebo treatment.


PHARMACY IN FOCus - 41


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