Nilotinib used to treat leukemia has improved symptoms in patients with Parkinson’s disease. It acts on motor and cerebral functions.
New hope for patients with Parkinson’s disease: a molecule effective against leukemia improves parkinsonian symptoms. Nilotinib is currently recommended by US authorities for the treatment of blood cancers. In a phase 1 clinical trial intended to verify its tolerance in patients, it showed an unexpected improvement in motor functions.
This neurodegenerative pathology can be recognized by three main signs: patients often tremble at rest. Their movements are slow and difficult, especially precise gestures. The too much tension in their muscles also stiffens their limbs. Disorders due in part to the lack of dopamine, a neurotransmitter involved in many brain functions. The process of autophagy, a degradation mechanism that removes waste products in the cell, is also impaired.
Complementary study
Nilotinib is known to inhibit a protein called tyrosine kinase. In Parkinson’s patients, this has the effect of re-triggering autophagy and breaking down toxic proteins. The molecule is also able to cross the blood-brain barrier, a kind of natural shield that protects the brain from external attacks. Normally, this barrier is beneficial, but it also blocks a lot of drugs, which complicates treatment for neuronal diseases.
To verify these faculties of nilotinib, a second clinical study was conducted in twelve patients with advanced forms of Parkinson’s disease. For six months, the researchers gave them daily doses of 150mg and 300mg, much lower than the doses used against cancer. They also analyzed blood and cerebrospinal fluid samples collected before the study, then 8 and 24 weeks later. The patients were followed by physical and neurological examinations, and electrocardiograms. Good absorption of the molecule was measured at different intervals after administration, as well as various biomarkers associated with Parkinson’s disease.
Improvements in symptoms
Throughout the treatment, the participants’ motor functions and cognitive performance improved, despite the reduction in usual treatment which compensates for the lack of dopamine. Scientists found, however, that the effects reversed some time after stopping nilotinib.
Biological markers also gave positive signs. Homoranillic acid, which indicates the production of dopamine, was thus multiplied by 2. The markers of oxidative stress were halved and the indicators of cell death fell significantly in the cerebrospinal fluid. These results suggest that fewer neurons were destroyed.
Most patients were able to cut back on dopamine compensation, some even discontinued it altogether without loss of motor and brain function. Note all the same, an increase in psychotic symptoms (hallucinations, paranoia and agitation).
“If we can validate the effects of nilotinib on cognitive functions by a large-scale placebo-controlled study, this molecule could become the most important treatment for Parkinson’s since the discovery of Levodopa fifty years ago”, enthuses Doctor Charbel Moussa, one of the authors of the study. The molecule could also be the first treatment of other still incurable dementias, such as those known as “Lewy bodies”.
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