Diabetes Shot Boosts Motor Function for Patients with Parkinson's

The investigators, led by University College London (UCL) in the United Kingdom, say that the drug was well tolerated and that the encouraging results pave the way for a larger trial to formally test whether or not the drug actually stops nerve cells from dying.

He explains that current treatments for Parkinson’s disease can relieve many of the symptoms, sometimes for years, but they do not stop the disease from getting worse.

Parkinson’s disease is a brain-wasting disorder that primarily attacks a part of the brain known as the substantia nigra. As it progresses, it destroys the neurons, or nerve cells, that make dopamine, which is a chemical messenger important for controlling movement.

Worldwide, there are more than 10 million people living with Parkinson’s disease, including around 1 million in the United States.

Symptoms of Parkinson’s disease include: tremors in the face, jaw, limbs, and hands; impaired balance, gait, and posture; muscle rigidity; problems with speech; fatigue; and sleep disturbance.

In most cases, Parkinson’s symptoms only become apparent after a large proportion of dopamine cells have already been affected.

Despite much research, we do not yet know what causes Parkinson’s disease. Many experts believe that the trigger is a combination of genetic and environmental factors.

Drug stimulates GLP-1 receptors

The drug exenatide is already licensed for the treatment of type 2 diabetes. It is a synthetic version of a substance that was originally discovered in the saliva of the Gila monster lizard.

In the treatment of diabetes, exenatide stimulates GLP-1 hormone receptors in cells of the pancreas, causing them to produce insulin.

Previous studies have discovered GLP-1 receptors in the brain, and laboratory tests have also shown that activating them produces a number of changes that might be useful for treating Parkinson’s disease. These effects include an increase in dopamine connections, improvement in energy production, reduced inflammation, and switching on of survival signals in nerve cells.

In their study paper, Prof. Foltynie and colleagues also refer to studies of animal models of Parkinson’s disease that have shown that exenatide can cross the blood-brain barrier.

These studies also found that the drug may protect and restore cells through its effect on GLP-1 receptors “at doses similar to those used in type 2 diabetes, resulting in improvements in motor performance, behavior, learning, and memory.”

The team followed this with a small, open-label trial that found that exenatide led to improvements in movement and mental assessments in patients with Parkinson’s disease.

Placebo-controlled trial

The new study builds on this previous work and strengthens the evidence in support of continuing to test exenatide as a treatment for Parkinson’s disease.

For the new trial, the team recruited 60 patients aged between 25 and 75 with moderate Parkinson’s disease, all of whom were attending a single treatment center, and they randomly assigned them to two groups.

Both groups injected themselves every week for 48 weeks. In one group the injections contained 2 milligrams of exenatide, whereas the other group injected themselves with a placebo.

The trial was double blind, so neither the participants nor the drug administrators knew which patients were receiving the active drug and which were receiving the placebo.

Both groups continued with their existing medication during the 48 weeks of injections. The 48-week period was then followed by 12 weeks during which the patients came off all their medications (the “washout period”).

Promising results

The results showed that after the 48-week treatment period, the exenatide group had increased scores on a recognized Parkinson’s motor function test that measured items such as agility, speech, and tremors.

A repeat of the test after the 12-week washout period showed that the improvement persisted after medication ceased.

In contrast, the placebo group showed a decline in motor scores, both at the 48-week and the 60-week point. The average difference in scores between the two groups showed an advantage of 4 points on a 132-point scale, which the researchers found to be statistically significant.

“This is the strongest evidence we have so far that a drug could do more than provide symptom relief for Parkinson’s disease.”

Prof. Tom Foltynie

The patients themselves did not report their symptoms improving more than that which their existing medication was doing for them.

Further studies will be needed to find out if exenatide actually alters the course of the disease, and the researchers suggest that it will be several years before it could be approved and ready for clinical use.

Meanwhile, they urge clinicians and patients to hold back from using it to treat Parkinson’s disease.

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