Medical Research. 2011 in Review
Medical treatments bring new ideas to the forefront. Take a look at the new ways scientists researching PD therapies. I hope this article brings hope to you as you look forward to all that 2012 has to offer.
New Ways to deliver medicine
Up to this point levodopa is available in a fast release or controlled release pill. A dissolvable fast release form Parcopa was developed for people with swallowing difficulties. Each of these forms is potentially associated with the need for frequent dosing, motor fluctuations
Innovative delivery systems are designed to rapidly reduce off states, manage absorption variability posed by problems such as protein
or prevent the on-off fluctuation seen with standard pill therapy by continuous delivery.
The following levodopa preparations are under investigation:
- 2nd generation extended release levodopa pill- designed to achieve rapid or more sustained blood levels
- Nasal levodopa- allows rapid absorption through nasal passages into the brain
- Continuous intestinal infusion of levodopa- levodopa in a gel format is infused directly into the intestines via a stomach tube. The benefits of this include continuous delivery and fine titration of dose as needed. Surgery is needed to insert the stomach tube and the pump is connected to an external pump that can be worn around the waist or holster.
Focus on more than just dopamine
- Glutamate antagonists- Amantadine has antidyskinetic properties and is already available to reduce dyskinesia in PD. Inconsistent effect and side effects may limit use. Additional antiglutamate medicines such as talampanel and ADX48621 are undergoing testing
- Adenosine receptor antagonist- These compounds may increase dopamine levels. Istradephylline may not have succeeded but preladenant is being studied in early PD.
- Calcium channel blockers- The anti hypertensive, isradipine, restores the sodium calcium balance for dopaminergic cell activity
- Diabetes drug Pioglitazone shows neuroprotective promise in animal studies and is undergoing phase 2 studies in early PD. This drug influences hormone status and has anti-inflammatory and antioxidant effects.
- Cholesterol medicine- Statin medicines reduce the risk of developing Parkinson’s and show promise in protecting dopamine nerve cells in animals.
Neurotrophic factors enhance and promote the life and growth of nerve cells. A successful agent would dramatically change how PD progresses.
- Cere 120 study uses the growth factor Nurturin (similar to GDNF). It requires surgical implantation into the brain. Initial studies showed some promise over a two year period so further testing is underway.
- Cogane (PYN50028)- a nonpeptide neurotrophic factor that can be taken by mouth showed promise in animal studies which have lead to a small phase 2 trial in early PD.
Medicines that treat nonmotor problems
- Clozaril and quetiapine are current antipsychotics used in PD yet no clinical trial has directly led to an FDA indicated treatment for this medicine related problem in PD. Most antipsychotics worsen PD since they block dopamine. A placebo controlled trial is underway to test pimavanserin a medicine that affects serotonin.
Cognition- Available treatments for Parkinson’s dementia include rivastigmine an acetylcholinesterase inhibitor that increase acetylcholine activity. Safinamide represents a new compound that enhances dopamine and blocks glutamate and is studied in a placebo controlled trial.
Orthostatic hypotension- A drop in blood pressure when standing leading to dizziness and even loss of consciousness. Droxidopa a precursor of norepinephrine used in Japan is being studied for this problem.
- Impulse control- often seen with dopamine therapy especially dopamine agonists. Naltrexone a receptor blocker is being tested for this problem
The treatment lies within. Lifestyle and personal factors do make a difference.
- Guided imagery a therapy that taps into the relaxation response can reduce tremor
- Mediterranean diet reduces the risk of developing Parkinson’s disease
Exercise modifies the course of disease and research is exploring its possible neuroprotective effects. Studies examining the effect of aerobic, anaerobic, dance, tai chi and yoga are just some of the examples of studies underway.
Gene therapy and Stem Cell therapy will be explored in future series
Author: Monique Giroux, MD