Alzheimer’s disease: use of a cancer drug?
Alzheimer’s dementia is the most common age-related neurodegenerative disease. Curable it is not yet. However, due to certain medicines, symptoms and concomitants the disease can be alleviated. A cancer drug could be used.
In spite of the great increase of Knowledge of recent years and the development of new drugs for the treatment of Alzheimer’s disease stagnated. As the German society of neurology e. V. (DGN) writes in a recent communication, disappointed, full of hope therapy approaches in the clinical trial. However, a Phase 2 study as a positive Signal for the use of Nilotinib, is actually a cancer drug is now available, for the treatment of Alzheimer’s disease.
Protein were reduced deposits
Alzheimer’s disease is the most common Form of dementia. In Germany alone, around 1.2 million people are affected. Stop the disease is yet to be. However, there are ways to treat Alzheimer’s disease and their sequelae. Possibly also with the cancer drug Nilotinib. This is already used for the treatment of a certain Form of leukemia.
Nilotinb is a so-called tyrosine kinase Inhibitor and blocks specific steps in the metabolism of cancer cells and inhibits their growth, declared the DGN. In Alzheimer’s disease, a chronic neurodegenerative disease, it comes to the production of defective or misfolded proteins (Beta-Amyloid, Tau Protein), which are deposited in the brain of the Affected in the Form of Plaques, or as a fiber-like fibrils.
Nilotinib is reduced in Alzheimer’s animal model deposits protein and promotes their degradation. In a Phase II clinical study were randomized, double-blind, placebo-controlled safety and tolerability of the substance, as well as their pharmacokinetics or the effect on different Alzheimer’s biomarkers studied.
37 Diseased (including 27 women) between 50 and 85 years (mean of 70.7±6,48 years) with mild to moderate Alzheimer’s dementia were initially set for at least a month to be stable on a single drug therapy (Acetylcholinesterase inhibitors, galantamine, Rivastigmine, or Donepezil). According to the figures made original investigations of the brain (positron Emission tomography, and MRI) and spinal fluid (cerebrospinal fluid).
The patients were randomized 1:1 into two groups and 150 mg of Nilotinib received more than 26 weeks, either orally, once daily, followed by 300 mg daily for a further 26 weeks or Placebo.
Drug was well tolerated
As a result, the PET imaging showed that, in the Nilotinib group, the Amyloid Plaques in the frontal lobe of the brain compared to the placebo group significantly had decreased. In the cerebrospinal fluid relevant concentrations of Nilotinib were detectable; in addition, the concentration of Beta-Amyloid-40 fell already after six months, and from Beta-Amyloid-42 after twelve months.
Also, the Tau Protein-lot (“Phospho-Tau-181”), it was after six and twelve months on the decline and volume loss of the Hippocampus, a brain region for memory is important, was in the MRI image pronounced after twelve months, 27 per cent lower than in the placebo group.
Nilotinib was well tolerated by the patients well, with 300 mg, there were more side effects (especially mood swings) than with 150 mg. Serious adverse events there were in the Nilotinib group, in the placebo group, a total of five events occurred in three Patients (rhabdomyolysis, Bronchitis, hypotension, dizziness attack). Serious cardiac side effects (such as they are in the field of Oncology under 600 mg/d described) wasn’t there but.
Exploratory clinical Tests such as the MMST (“Mini-Mental-Status-Test”) and ADAS-Cog (“Alzheimer’s Disease Assessment Scale“) for the objectification of cognitive abilities (orientation, memory, attention / calculation ability, language) showed no significant differences between the groups, but a trend towards better values in the Nilotinib group.
The results of the study were published in the journal “Annals of Neurology”.
Positive Signal for Alzheimer’s research
“This relatively small study has investigated primarily the safety, tolerability, and effects of Nilotinib on Alzheimer’s biomarkers, and successfully,” explains Professor Dr. Richard Dodel, Geriatrician and neurologist at the University of Duisburg-Essen.
“The study had few patients and was not designed to enable a course assessment of dementia. Nevertheless, we hope that the positive Trend in terms of the cognitive Tests in the future, in large clinical trials to confirm. May be you have to treat the patients in the earlier stages of the Disease, long-term disease-modifying see the end of benefits,“ said the doctor.
“After the negative outcome of studies on different, first of all, very hopeful therapeutic approaches this study is a positive Signal for Alzheimer’s research. In view of the increasing Numbers of those Affected, we are in a race against time. An effective therapy that stops the Progression of the disease, would be a blessing for the entire humanity,“ says Prof. Dr. Hans-Christoph Diener, spokesman of the DGN. (ad)