Gene therapy helped macaques with parkinsonism
Parkinson's disease is a widespread neurodegeneration that severely impairs a person's ability to move. The authors of the new study created a new experimental treatment method - gene therapy - and showed its effectiveness on mice and macaque monkeys modeling Parkinson's disease.As life expectancy increases, the world's population is steadily aging. There are more and more elderly people in the world, and thus more age-related diseases. These are primarily neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.
The main symptoms of Parkinson's disease include motor disorders - muscle stiffness, tremor, decreased motor activity, posture problems and so on. There are more than six million patients with this diagnosis worldwide and it is predicted that many more will soon be diagnosed.
Parkinson's disease develops due to the death of neurons in an area of the brain called the substantia nigra. These are the cells that synthesize the dopamine needed to transmit nerve impulses. As a result, patients experience an acute deficiency in this neurotransmitter, which leads to the development of characteristic symptoms.
Treatment is intended to compensate for the deficiency of dopamine, e.g. by using its precursor levodopa. However, such drugs act on many nerve cells, not just the right ones, which causes severe side effects.
Scientists are therefore seeking to develop more selective treatments for Parkinson's disease. The authors of a new publication in the journal Cell have created a new method of gene therapy with high specificity and controllability, which combines three different approaches. First, they use the envelope of an adeno-associated virus, in which they have made many mutations, to deliver the drug. These made the viral particle move more directionally along the axon of the neuron to its body. Second, specific promoters - regions of DNA that regulate its rewriting into RNA form - were introduced into these particles, which are particularly active in the right neurons. Finally, the construction as a whole was made controllable with the help of a special substance-activator, which "turns it on" (and at the same time the target neurons) when introduced from outside.
The researchers immediately tested the new method on animal models of Parkinson's disease - mice and primates (namely crab-eating macaques). In order to induce parkinsonism - symptoms similar to Parkinson's disease - the animals were injected with specific drugs toxic to the brain, 6-hydroxydophamine (6-OHDA) in mice and 1-methyl-4-phenylpyridinium (MPP+) in macaques. As a result, the animals developed characteristic movement disorders - slowness, stiffness, decreased overall activity, and so on.
Fortunately, after the experimental drug was administered, both mice and macaques got better: motor disorders decreased. At the same time, the effect of the new approach was, as expected, strictly selective and was successfully activated by "activating" drugs. Moreover, it was maintained longer than in the case of levodopa.
It is important to emphasize that the method used does not involve the introduction of foreign genes from outside - only the activation of the patient's own neurons. This approach is less risky and therefore can be adopted more quickly by practitioners.