A lay summary written by Rachel Grasmeder Allen & reviewed by Dr Scott Allen.
Typical medicines, such as a tablet or an injection, often have problems reaching the central nervous system (CNS) in the body; the CNS is the brain and the spinal cord and together they control most bodily functions. When something goes wrong with the CNS, as it often does in many diseases, it makes it hard to treat the problem when tablets and injections don’t enter the CNS properly to treat the problem.
One way scientists have tried to overcome this is through the use of nasal sprays and nasal drops; the medicine (drug) is in the spray or drops and when it enters the nose, the drug can get into the CNS. In this study, they used nasal drops and used these to deliver mitochondria to rats.
Mitochondria are organelles, these are small parts of the cell that have a specific job. In the case of mitochondria, their main job is to produce energy for the cells. In people with Parkinson’s disease (PD), their mitochondria are damaged in their brain and so they no longer work as well. This means less energy is produced and without sufficient energy for normal cell function, these cells become damaged and die. This is particularly a problem in the brain because it requires a lot of energy.
People with PD have problems with their movements, they have a tremor (their arms and hands shake) and they experience stiffness in their limbs. This is because their dopaminergic neurons (the cells in the brain that are involved in controlling movement) are damaged, due, in part, to loss of efficient energy production. Scientists are currently looking for treatments to fix or replace the mitochondria in PD patients, specifically in these dopaminergic neurons.
In this study they used a PD rat model. To produce this PD model, rats were given a drug (6-hydroxydopamine) which destroys their dopaminergic neurons (the cells that are damaged in PD) and gives them similar movement problems to those seen in PD patients. After this, the rats received treatment. There were five groups of rats. The first group were not given any treatment, the second group were given nasal drops but these did not contain mitochondria, the third group were given nasal drops containing mitochondria, the fourth group were given nasal drops containing Pep-1 mitochondria (Pep-1 is a protein that increases the number of mitochondria that can get into cells) and the fifth group were only given nasal drops with Pep-1.
Rats were assessed three months after the treatment. It was found that in the rats given the mitochondria treatment, they regained normal locomotor activity (moving from place to place) and balance. These rats displayed less ‘PD symptoms’. This suggests that the mitochondria treatment worked. They then looked at the dopaminergic neurons in the rats and found that these survived better in the rats which received the mitochondria treatment. This implies that the mitochondria treatment helped these neurons survive, as expected.
The authors compared the results of this study to a previous study they had published. In this previous work, they used the same PD rat model but the rats were given an injection containing the mitochondria into their brain, rather than the nasal drops. They found that the improvement in behaviour and neuron survival was similar in the injected rats compared to the rats who received nasal treatment. One difference between the injection and the nasal treatment was that inflammation was higher in the rats who received the injection compared to the nasal treatment.
Inflammation is the body’s reaction to new, foreign substances that enter it. The aim of inflammation is to destroy this foreign substance if it is harmful, to protect the body. For the mitochondria treatments, it is best to have minimal inflammation in response to the injection or nasal treatment because in this case, the inflammation is not necessary and would cause more harm than good.
Therefore, the nasal drops seem to be the better treatment because this treatment works just as well, but there is less inflammation, making it overall the preferable treatment. It is also less invasive, which is another major advantage.
In conclusion, this group found that using a treatment of nasal drops containing mitochondria is a successful way to improve induced PD symptoms in rats, and increase the survival of dopaminergic neurons. It is potential that this method of treatment could progress to be used in a clinical setting to treat patients, but more testing is needed first.