Anle138b Prevents Clumping of Alpha-Synuclein Protein

In Parkinson's disease and Lewy body disease, Lewy bodies form in nerve cells. These abnormal clumps are aggregates of alpha-synuclein protein and are highly toxic to nerve cells. By the time the first symptoms of Parkinson's or Lewy body disease appear, many nerve cells have already been lost. Now, researchers have developed a chemical compound that inhibits the clumping of alpha-synuclein and slows down the onset and progression of Parkinson's disease in mice.

The chemical compound is called Anle138b. It works by reducing the rate of growth of the alpha-synuclein protein deposits and delaying the degeneration of nerve cells. It has been tested on mice that were raised to develop Parkinson's disease. Mice treated with Anle138b remained disease-free longer than untreated mice.

This research was carried out at Ludwig Maximilian University of Munich and the Max Planck Institute for Biophysical Chemistry in Göttingen. The researchers tested 20,000 substances for their ability to block formation of the protein deposits. They found that Anle138b was the most promising, and it is tolerated well at high doses, can be administered with food, and can reach high levels in the brain.

Interestingly, Anle138b also seems to inhibit the clumping of other toxic proteins that occurs in Alzheimer's disease and in Creutzfeldt-Jakob disease. The next step is for researchers to conduct toxicity tests on mammals other than mice.

A press release about the study is available.

This research is reminiscent of another study reported last year by a team at UCLA. They developed a compound that prevents the clumping of alpha-synuclein. Alpha-synuclein is common in the brain (although its function is not understood) and seems to present a problem only when it clumps together. The researchers found that their compound (which they referred to as a "molecular tweezer") prevented alpha-synuclein from forming aggregates and even broke up existing aggregates, with no toxic side effects on normal, functioning brain cells. They demonstrated this in cell cultures. They then repeated the study on zebrafish that had been modified to develop Lewy bodies and found the same effects. Work continues now on mice.

A press release about the study is available. The scientific paper was published in Neurotherapeutics.