A drug that will facilitate the memory of Alzheimer's patients at the beginning of their disease

An original development by Tel Aviv University was found to protect memory in clinical tests in elderly patients
Brain swelling in Alzheimer's patients.

Courtesy of Alon Therapytex

A successful clinical trial of a new substance, 108-AL, which may treat Alzheimer's disease, is based on an original Israeli discovery from the laboratory of Professor Ilana Gozes* from Tel Aviv University. The experiment was recently carried out by the Canadian company ALLON THERAPEUTICS**, founded by Prof. Guzes. According to the company's publications, the experimental drug was found to be effective in improving the memory and learning functions of people with mild cognitive impairment, the type that usually predicts the onset of Alzheimer's disease. Patients who received for 12 weeks a high dose of the drug - which is administered as a nasal spray, discovered an impressive improvement in tests measuring short-term memory, working memory and recognition ability - abilities that are severely impaired in Alzheimer's patients. A very significant finding showed that the positive effect was maintained even four weeks after stopping the administration of the experimental drug.

Alzheimer's disease, which affects about 7.5% of the population over the age of 65, and about a third of the elderly over the age of 85, is currently considered incurable, and the effect of the existing treatments is limited and short-lived. This is despite the unceasing efforts of researchers around the world to find an effective solution to the enormous plight of those afflicted with the disease and their families. The success of the new experimental drug may give hope to many millions around the world - a hope that first germinated in a laboratory at Tel Aviv University.

"The active substance in the drug is a very short protein called NAP, a fragment of a longer protein called ADNP," explains Prof. Gozes. "We discovered ADNP in the 90s, and recently found that it is responsible for controlling about 400 genes, related to cell differentiation in general, and nerve cells in particular, during embryonic development. Our experiments have shown that ADNP plays an extremely important role in brain function, but since it is a very long protein, no drug can be based on it. That's why we looked for a small section of it, which can preserve the vitality of nerve cells, and that's how we arrived at NAP. We estimate that this substance can be used as a basis for drugs for a wide range of diseases and brain injuries." (Prof. Gozes's research on the ADNP protein was published last year in leading international journals:

Developmental Biology, Journal of Pharmacology and Experimental Therapeutics, Journal of Biological Chemistry).

In order to develop medicines based on the discoveries in her laboratory in Tel Aviv, Prof. Gozes founded the biotechnology company Allon Therapeutics Inc., which bears the name of her father, the late Yitzhak Allon, and operates in Vancouver, Canada. According to Prof. Gozes, the company took an innovative scientific approach in the search for an answer to Alzheimer's:

"The brains of Alzheimer's patients have two main characteristics: the accumulation of plaque consisting of the beta amyloid protein segment outside the nerve cells in the brain, and the entanglement of protein threads consisting of the tau protein - TAU - inside the nerve cells. In contrast to other studies, the "Alon" technology focuses mainly on the entanglement of the threads of the TAU. Also, this is the first experimental drug that has reached the stage of advanced clinical trials, which apparently affects both characteristics - beta amyloid and TAU - at the same time: in experiments on mice with Alzheimer's characteristics (in collaboration with researchers from Georgetown University), a reduction was discovered of 70% in the biochemical process that creates the complications of TAU, a 20% decrease in the level of the amyloid plaque protein, and a significant improvement in cognitive abilities." (The studies were published in the Journal of Molecular neuroscience, 2007 and in the April 2008 issue of the Journal of Pharmacology and Experimental Therapeutics (.

The next question was: Is the drug also effective in humans?
The first stage of the human trial is to make sure that the 108-AL is a safe substance to use. This phase was successfully completed in March 2007. From here, Allon Therapeutics advanced to the second phase: testing the drug's effect on humans in a condition considered pre-Alzheimer's. 144 subjects, men and women aged 55-85, were divided into three groups: a group that received a placebo, a group that received a low dose of 108-AL, and a group that received a high dose, twice a day - all for 12 weeks. All the subjects underwent a series of tests to measure their cognitive abilities - at the beginning of the experiment, during it, at the end, and also a month after its end.

"And it worked!" Prof. Gozes says with satisfaction. "The findings were unequivocal and extremely impressive." In one of the tests, a 62.4% (!) improvement in short-term memory was discovered in the subjects who received a high dose. In another test, which examines short-term memory, active memory and language and speech processing processes, an improvement of 17.2% was found, which is also statistically and medically significant.

The success of the second phase of the clinical trial, which was reported at the end of February 2008, caused a significant increase in the shares of Allon, which is traded on the Canadian stock exchange and leading investors are showing interest in its activity. All of these will undoubtedly help her to raise the necessary capital to carry out the next step: a clinical trial in mild to moderate Alzheimer's patients, which is expected to begin during the year 2008 (according to the company's publications on the website). In addition to Alzheimer's, Allon is engaged in the search for drugs for other brain-related diseases and injuries, drugs that are also based on the short protein segment NAP. Experiments being conducted these days are testing the effectiveness of the company's products in treating the cognitive impairment typical of schizophrenia, and the mild cognitive decline that occurs following bypass surgery. Other targets include drugs for Parkinson's disease, stroke damage and other injuries to the central nervous system. And all with the help of one tiny protein segment, discovered in a laboratory in Tel Aviv.

* Prof. Ilana Gozes from the Department of Human Molecular Genetics and Biochemistry of the Sackler Faculty of Medicine, is the trustee of the Lilly and Abraham Gildor Chair, and serves as the head of the Adams Brain Research Center at Tel Aviv University. For her outstanding achievements in applied research, as reflected in the number and variety of inventions and patents, Prof. Guzes won the 2007 Applied Research Award of Tel Aviv University.

** ALLON THERAPEUTICS was established in collaboration with the Ramot company near Tel Aviv University, and is a business partner for the development of medicines based on the inventions and research of Prof. Gozes and her colleagues at the university and the American Institutes of Health (NIH). The foundation of the company is based on an investment by the Institute for Study of Aging (ISOA) and an initial investment by Ephraim (Efi) Gildor. The company's rapid progress is due to Canadian investment, along with the excellent management of the president and CEO Mr. Gordon McCauley, in collaboration with Prof. Guzes, who advises as the chief scientist, and the dedicated staff.