Israeli Drug Makes Alzheimer’s Symptoms Disappear in Mice

Despite optimism, bitter truth is that over 99 percent of clinical trials for Alzheimer’s treatments end in failure.

Bloomberg

A new drug under development by Israeli scientists to fight Alzheimer’s disease has led to the complete disappearance of symptoms in mice used as a model for the sickness. These mice have shown similar cognitive capabilities to healthy ones after taking the drug. The study of the mice was conducted after excellent results were reached with neuron cultures, in which a tiny concentration of the drug succeeded in preventing the destruction of nerve cells — which had been exposed to damage characteristic of oxidative stress or amyloid beta plaques.

For now, it is much too early for the new drug to help Alzheimer’s sufferers, but the scientists say their preliminary findings present a worthy candidate for a future treatment for a disease that is incurable today.

“I describe the molecule we developed as a sort of ‘Swiss army knife.’ It is capable of carrying out a large number of therapeutic tasks and works on a number of targets at the same time,” Prof. Bilha Fischer, a chemistry professor at Bar-Ilan University, told Haaretz. Fischer is developing the new drug in cooperation with Prof. Daniel Offen, a neuroscientist at Tel Aviv University Medical School.

Medical science has been this optimistic before about finding a cure for Alzheimer’s, but in most cases the scientists, patients and their families have suffered serious disappointment. The bitter truth is that over 99 percent of all clinical trials for Alzheimer’s treatments end in failure. For now it is not only incurable, but a major mystery and irreversible. The chemical basis for the disease is still unclear. The research is directed in many directions and based on very different assumptions and approaches.

One focus in recent years is based on the “amyloid assumption,” which says the amyloid beta peptide plays a major role in the development of the disease. The accumulation of the “sticky” amyloid protein plaques is responsible for the damage, by building up into clumps that can cause inflammation in the brain and the death of neurons. These plaques are the main target of most Alzheimer’s research today. Almost 90 percent of the scientific resources in Alzheimer’s research are devoted to developing drugs and treatments to reduce the concentrations and activity of amyloid beta in the brain.

Small molecules

AP

If some progress is being made in the battle against Alzheimer’s, it can be found mostly in the development of tools for early diagnosis of the disease, as well as in research on the link between lifestyle changes for patients and a slowing of the disease. Drug development still lags far behind. “Today, there are drugs whose effectiveness is very limited. They affect only about 20 percent of the patients and for a period of a year to two,” says Fischer.

The main reason for this lack of progress is the multi-dimensionality of the disease and the inability to treat it through only one dimension, a single therapeutic target, as has been done in most trials so far, she says. In addition, many of those developing therapeutic approaches are not chemists or pharmaceutical developers, but biologists who adopt approaches such as using antibodies against beta amyloid for treatment. “We come from the direction of development of small molecules as drugs,” explains Fischer.

The new molecule succeeds in effectively breaking up the accumulation of the amyloid beta, which damages nerve transmission, while at the same time also succeeds in activating specific proteins that provide a defense for neurons from various materials characteristic of Alzheimer’s. “In the lab we saved neurons [of new-born rats] which normally would die under conditions of oxidative stress or in the presence of amyloid beta. These cells survived quite well when treated even with very low concentrations of our material,” says Fischer.

The series of tests conducted on the mice included testing their orientation ability, behavior, learning and memory — and for all of which the results were positive, and the mice’s cognitive abilities were similar to those of healthy mice, she says. “It was encouraging. We need to remember that the disease starts 20 years before it is diagnosed. Since the diagnosis ability today is better than the ability to cure, the scenario we can hope for is that as we can diagnose the disease in earlier stages, so we can prevent the progress of the disease using the drug. It could be an enormous achievement in dealing with this challenging disease,” she says.

The amyloid beta, even though great resources are being poured into understanding and fighting it, is not the only target — and it does not reveal the sources of the disease and the mechanisms that cause it. One of the other interesting directions being studied concerns the immune system. In recent years, the approach that the development of Alzheimer’s is linked to a disruption of the dialogue between the brain and immune system is taking hold. This approach contradicts what was once the accepted position that a complete separation exists between brain cells and the immune system.

“Twenty years ago I claimed it was not possible evolutionarily for the brain to give up on the help of the immune system,” says neuro-immunologist Michal Schwartz of Weizmann Institute of Science. In addition to the plaque build-up there is local inflammation, and while such an immune response is usually good, when it does not end is becomes pathological, she said.