What is Parkinson's disease

Negative points that Parkinson's brings

A widely used drug for the treatment of asthma, the popular salbutamol (or Ventolin), can open the way to prevent Parkinson's disease and improve its treatment, according to research led by the Harvard Medical School (USA). presents this week in the journal Science.
The authors of the work have shown that the drug counteracts a protein called alpha-synuclein, which is considered the main suspect in causing and progressing the disease.

 

In other research presented this week, scientists at Kyoto University (Japan) have obtained neurons from stem cells in the laboratory and successfully implanted them in the brain of cynomolgus monkeys, a species of Southeast Asian primates.

According to the results published in Nature, the treatment has alleviated symptoms of the disease and has not caused any significant side effects in the two years after the intervention. In this case, a neurotransmitter called dopamine, whose deficit causes the most characteristic symptoms of Parkinson's, as involuntary movements, has been restored.

Research sets the basis for testing therapies in people

 

Both investigations lay the foundations for testing treatments in patients. "We hope to start a clinical trial by the end of 2018," says Jun Takahashi, director of stem cell research.

 

Clemens Scherzer, director of drug-based research, also says that "we are working towards clinical trials", but without specifying when they will begin.

 

"These are complementary investigations that focus on the two main molecules involved in the disease," says Maria Josep Martí, coordinator of the Parkinson's unit at the Hospital Clínic in Barcelona. Acting on alpha-synuclein could slow the progression of the disease "if the hypothesis that this protein is responsible for such progression is confirmed". Acting on dopamine with neuronal implants could improve the control of your symptoms. But Martí warns that it is still too early to know if these therapies will be effective and safe.

 

How parkinson's disease spreads in the brain

 

The treatment of Parkinson's has relied on the last 50 years to restore dopamine in the brain with the drug levodopa, a breakthrough that changed the lives of patients and received the Nobel Prize in Medicine in 2000. However, Parkinson's disease It progresses even in people treated with levodopa and the dopamine deficit does not explain all its symptoms. These observations suggest that alterations of dopamine are not the cause of Parkinson's disease but one of its consequences.

 

The discovery that most patients have abnormal accumulations of alpha-synuclein in the brain has suggested that this protein could be a cause. In addition, in families where there are more cases of Parkinson's, genetic alterations have been identified that cause an excess of alpha-synuclein. This has led pharmaceutical companies to look for molecules to eliminate alpha-synuclein from the brain.

 

Researchers at Harvard Medical School have opted for a different strategy and have sought drugs, not to eliminate alpha-synuclein when it has already accumulated, but to prevent it from accumulating from the beginning. These drugs, they argue, could be useful to prevent the disease from progressing from the moment it is diagnosed.

 

Asthmatics treated with Ventolin have a 34% lower risk of Parkinson's.

 

To search for them, they have analyzed more than 1,100 drugs already approved for other ailments to see if any of them have any effect on alpha-synuclein. They have discovered that the so-called beta-2 adrenergic receptor agonists counteract this protein. The most popular of these is the salbutamol that is prescribed for asthma.

 

After reviewing data from four million people in Norway in a collaboration with the University of Bergen, researchers have calculated that the risk of Parkinson's is 34% lower among those who are medicated with salbutamol than in the rest of the population. Conversely, those who take propanolol, which has the opposite effect on alpha-synuclein, have a twice as high risk.

 

"If, from these observations, the progression of the disease is halted, it would also deserve a Nobel Prize. But clinical trials will have to be carried out to check to what extent this strategy is useful for patients, "says Oriol de Fàbregues, a clinical researcher specializing in Parkinson's at the Vall d'Hebron Institute of Research (VHIR).

 

The Japanese team bases its therapy on neurons obtained from iPS stem cells.

 

The team from the University of Kyoto, for its part, has explored the possibility of restoring part of the neurons that parkinsons destroy. Unlike other research groups that advocate implanting stem cells directly into the brain, Takahashi and his team have chosen to manipulate stem cells to obtain dopamine-producing neurons in the laboratory. They have worked with iPS stem cells - that is, not obtained from embryos.

 

By implanting neurons and not stem cells, the theoretical risk of tumor formation is reduced. None of the eleven macaques in which the treatment has been tried has suffered brain tumors after two years. The animals, which have a disorder equivalent to parkinson's, have improved their mobility. Likewise, it has been proven by magnetic resonance how the neurons have taken root in the brain. "This is the first study to show that human neurons derived from stem cells are effective and safe in a primate model of Parkinson's disease," says Takahashi.