MONTREAL — A potential new Alzheimer’s drug being tested by
Canadian and Israeli researchers is showing promising results, its
discoverer said in Montreal.

Illana Gozes, director of the Adams Super Center for Brain Studies at Tel Aviv University (TAU), calls the research a breakthrough in the understanding of the disease’s pathology, which should lead to a treatment that can halt and even reverse its course.

The drug AL-108, which targets the neurofibrillary “tangles” in the brain that characterize Alzheimer’s disease, is being developed by the Vancouver-based biotechnology company Allon Therapeutics, which Gozes, its chief scientific officer, founded.

Gozes was in Montreal, at the invitation of the Canadian Friends of TAU and the Alzheimer Groupe, to report on the latest news about AL-108. “It is too early to speak of a cure, but there’s hope that we may be able to change the course of the disease” by treating what is thought to be the cause, rather than by reducing its symptoms, as currently available therapies do.

No drug on the market today has any impact on these tangles, or the other hallmark of Alzheimer’s, plaque accumulation in the brain, she said.

AL-108 was shown to improve short-term recall and what is termed working memory in a clinical trial involving 144 patients with abnormal forgetfulness, known as amnestic mild cognitive impairment (aMCI), which is considered a precursor to Alzheimer’s. The research confirmed that those tangles do indeed seem to interfere with specific types of memory function, perhaps as much as the plaque buildup. The subjects otherwise functioned normally.

Gozes said the human trials are consistent with several animal studies that found that AL-108 reduced the tangles located inside neurons and increased memory function. In animals, AL-108 also reduced the plaque, which is outside neurons.

In people, the drug was found to be safe and produced no serious side effects – a small percentage of the subjects reported headaches, nasal congestion or irritation. AL-108 is administered through the nose in a spray.

The 144 patients, all Americans, were aged 55 to 85 years, and evenly divided between men and women. They were tested at 17 different centres, with the support of the U.S. National Institutes of Health.

They were divided into three groups: one was given a placebo, another AL-108 in a lower dose, and the third AL-108 in a higher dose over 12 weeks. The latter group, which received 15 milligrams twice daily, showed the most significant improvement in their memory, she said.

Before taking the drug or the placebo, the subjects were given widely used tests such as having to remember a series of numbers forward  and backward, and picking out an image from a set that had been shown to them a few seconds before.

They were given the tests again at intervals of four, six or eight weeks.

The results were most dramatic in the numbers test, and the improvement, which was observed after only four weeks, was maintained four weeks after the drug was stopped, Gozes said.

They did not, however, show any improvement in tests that involve planning or abstract thinking, which suggests that aMCI is not related to what’s termed executive function.

The drug is believed to target the regions of the brain associated with memory: the medial temporal lobe, hippocampus and prefrontal cortex.

AL-108, not only stops the formation of the tangles, but actually untangles them, she said. The drug is derived from naturally occurring proteins secreted by the brain, which have a protective effect against injury.

The tangles are the result of the degeneration of microtubules, the “conveyor belts” inside brain cells. The tangles occur when a protein called tau, which normally acts to hold the microtubules together, converts from a soluble to an insoluble form.

Gozes’ animal studies have shown that AL-108 reverses the microtubules’ deterioration and restores their density by increasing the levels of soluble tau.

Gozes and the clinical trial’s principal investigator, Donald Schmechel, a Duke University geriatrics professor, reported on AL-108 at the International Conference on Alzheimer’s Disease and Related Disorders held in Chicago this summer, which brought together more than 5,000 researchers, physicians and care providers from 60 countries.

Third-phase clinical trials on AL-108 are now underway, and the drug may be commercialized with five years. Allon Therapeutics (Allon is Gozes’ maiden name) is a publicly traded company listed on the Toronto Stock Exchange.

Allon is now also conducting trials of AL-108 on schizophrenia patients and coronary bypass patients who suffer cognitive impairment.