Scientists have long observed that a factor underlying the brain changes that lead to Parkinson’s disease (PD) is imbalances in the level of the element calcium. Building on this knowledge, new research in the July issue of Brain identifies one specific calcium ion channel as a marker for PD, supporting the idea that a family of drugs already on the market, calcium channel blockers, have potential to modify PD progression. Cells, including the dopamine neurons lost in PD, are constantly working to balance calcium levels by pumping it in and out through channels. Too little calcium means the cell will not work properly and in PD, scientists propose that too much calcium can stress and kill dopamine neurons.
Researchers led by Michael J. Hurley, Ph.D., of Imperial College London, investigated whether certain types of calcium channels make some neurons more susceptible to PD. They studied brain tissue (donated postmortem) from nine individuals who died without any brain disease and 18 people who died with PD. They used staining techniques to map the location of the different kinds (subtypes) of calcium channels in the brain.
- In the brains of people who died with PD, calcium channel subtypes were distributed differently than in the brains of people who had no neurological disease.
- Changes in calcium ion channel distribution were evident in the brains of people who had died with early stage PD.
- People who had died with PD had more calcium channels of one subtype, Cav1.3, throughout their brains.
What Does It Mean?
Building on the potential link between PD and calcium levels in neurons, this new study found that the distribution of calcium ion channels is different in people with and without PD, identifying a specific type of channel that is more prevalent in PD. Researchers suspect that overuse of this channel in PD may make cells susceptible to damage and death.
The new study supports the investigation of drugs that specifically target the calcium channel over-represented in PD to potentially slow disease progression. Drugs on the market that block calcium channels are commonly used to treat high blood pressure. One such drug, isradipine, which blocks a calcium channel different from the one that is identified in this study, is currently being investigated in the US for Parkinson's.
The natural sweetener mannitol, a common component of sugar-free gums and candies, may hold potential as a treatment for Parkinson’s disease (PD), according to a study funded in part by the Parkinson's Disease Foundation and published in the June 14 issue of The Journal of Biological Chemistry. Researchers took an interest in mannitol because, when given as an injection, it can reach the brain and it can stop some proteins from clumping together. This is interesting in light of the fact that clumps of the protein alpha-synuclein are a well-known sign of Parkinson’s disease.
Daniel Segal, Ph.D., and Ehud Gazit, Ph.D., at Tel Aviv University, in Israel, examined mannitol’s potential for treating PD in the lab, in fruit flies and in mice.
- In the test tube, injections of mannitol prevented alpha-synuclein from clumping into the Lewy bodies that form in the brains of people with PD.
- In the fruit-fly model of PD, mannitol injections restored the flies’ normal movements.
- In the same flies, mannitol reduced alpha-synuclein clumps by 70 percent.
- In parkinsonian mice, mannitol injections succeeded in (i) reducing alpha-synuclein clumps in areas of the brain that are affected by classic PD, and (ii) protecting dopamine neurons that die in PD.
What Does It Mean?
This initial study demonstrates the potential of mannitol to prevent the alpha-synuclein clumping that takes place in PD. The authors suggest that the natural sweetener appears to function as a “chemical chaperone,” meaning it stabilizes proteins like alpha-synuclein and prevents them from inappropriately clumping together.
However, PDF’s scientific advisors caution that there is a long stretch between improving the behavior of flies and treating PD symptoms in people. Researchers need to test the capacity of mannitol to improve PD symptoms in other animal models of PD. If the results hold up, then mannitol could be tested in clinical trials for the treatment of PD in people. Additionally, the results of this early study are not a suggestion to eat large amounts of sugar-free candy or chewing gum. Even if one was able to consume enough mannitol to reach the level that was fed to fruit flies, there is currently no evidence that it will ease Parkinson’s symptoms in people.