Gene therapy alleviates movement disorders typical of Parkinson’s patients, such as involuntary hand tremors and muscle stiffness, according to a study published in the Lancet Neurology journal.
This is the first such convincing evidence not only for the safety, but also the effectiveness of gene therapy in Parkinson’s disease and any neurological disease, emphasize the authors of the study. These studies prove that the hopes related to the use of gene therapy in neurodegenerative diseases (i.e. those that damage the nervous system – PAP) have become reality – comments Prof. Peter LeWitt of the Fenstein Institute for Medical Research in Manhasset, New York.
The neurologist and his colleagues from seven medical centers in the USA showed in a study on 45 patients with advanced Parkinson’s disease that in half of those who had the therapeutic gene introduced into the brain, movement disorders were significantly alleviated – involuntary limb tremors, muscle stiffness or problems with starting movement. On the other hand, in the group that underwent simulated therapy, this percentage was 14%.
In the past, there have been reports of the use of gene therapy in patients with parkinson’s – a progressive neurological disorder caused by damage to the neurons responsible for movement control, body balance and emotional regulation. However, the team of prof. LeWitt for the first time proved the effectiveness of this method in a study conducted according to the most respected standards in the scientific community. It was the so-called A double-blind, randomized trial in which neither the patients nor the investigators who were evaluating the effects of the treatment knew which patient was actually receiving treatment and which was having simulated therapy. This allows not only to distinguish the effectiveness of treatment from the placebo effect, but also eliminates the influence of the researcher’s suggestions on the assessment of the effects of the therapy.
Parkinson’s disease is caused by the degeneration of neurons in structures in the brain called the basal ganglia. The disease process begins in one of them – the so-called substantia nigra, where nerve cells that produce dopamine, a neurotransmitter responsible for the control of motor functions, body posture and the regulation of emotions, are damaged. This leads to movement disorders – trembling arms and legs at rest, shuffling, muscle stiffness, problems with facial expressions, but also to emotional disorders, e.g. difficulty reading other people’s feelings or depression.
When the symptoms of the disease are less severe, they can be effectively relieved with medication. The mainstay of therapy is levodopa, which is the source of dopamine in the brain. However, over time, the effects of pharmacotherapy weaken and side effects occur, such as uncoordinated movements.
Currently, deep brain stimulation is considered the most effective method of helping patients whose effectiveness has decreased. It involves the implantation of an electrical stimulator in the brain that reduces the activity of a structure called the low thalamic nucleus, which is involved in controlling body movements. In Parkinson’s disease, it is too active, because in addition to the decrease in dopamine levels, the concentration of the neurotransmitter that inhibits the activity of neurons, i.e. gamma-aminobutyric acid (GABA), also decreases – explains co-author Dr. Matthew During the work from Ohio State University.
However, deep brain stimulation only helps some patients, and besides, it does not alleviate some of the symptoms of the disease, such as balance disorders, problems with initiating movements and freezing, difficulty swallowing, speech disorders, and deterioration of mood or mental performance.
Gene therapy may be an alternative to this method, believe the authors of the latest work. It involves the insertion through the catheter of billions of copies of a therapeutic gene embedded in the genetic material of a harmless virus into the lowthalamic nucleus (in both hemispheres of the brain). The gene encodes the enzyme responsible for the synthesis of GABA – i.e. glutamic acid decarboxylase (GAD), and its introduction is to increase the production of this neurotransmitter.
The latest research involved 45 patients aged 30-75 years, who had been suffering from Parkinson’s disease for at least 5 years and had previously responded to levodopa therapy.
Almost half of them (22 people) underwent gene therapy, while the rest (23 people) underwent a simulated operation in which neurosurgeons only partially cut into the patient’s skull and were injected with saline subcutaneously instead of a solution with copies of the gene.
Only 16 patients in the gene therapy group and 21 patients in the control group were included in the final analysis. The rest have been excluded for various reasons, such as inserting a therapeutic gene twice into a lowthalamic nucleus in the same hemisphere.
It turned out that after six months in patients undergoing gene therapy, movement disorders alleviated by an average of 23%, while in the control group by about 13%. The improvement in motor functions was apparent about a month after treatment and remained unchanged throughout the six months of follow-up, emphasizes Dr. Michael Kaplitt from Weill Cornell Medical College in New York, who participated in the study. In 2007, in the pages of the Lancet weekly, he presented evidence of the safety of this gene therapy in patients with parkinson’s.
Her side effects were mostly related to the operation, relatively mild, and passed quickly. The most common were headache and vomiting.
The researchers believe their findings raise hope for the future use of gene therapy in Parkinson’s patients. At the same time, they emphasize that further research is necessary to verify their observations.
According to the author of the editorial, Michael Hutchinson of New York University, the most recent research has the advantage of being very carefully planned. However, a few questions remain: How long will the treatment effect last? Will introducing the genetic material of the virus into the brain bring any complications in the future? Does this technique have any advantage over deep brain stimulation, which is twice as effective? – the expert wonders.
Brain stimulation does not alleviate such a Parkinson’s symptom as freezing. The authors of the latest study indicate that gene therapy may produce better results, but they do not provide any statistical data, emphasizes Hutchinson.
Joanna Morga (PAP)