Numbers that cut amyloids - a cure for degenerative diseases (in recruitment) for the masses

A group of researchers from around the world, led by Prof. Gal Beitan from UCLA, are asking the public to raise 2 million dollars in crowdfunding, to conduct clinical trials of a drug that deals with the accumulation of substances in cells: Alzheimer's, Parkinson's, Lou Gehrig's, type 2 diabetes and other diseases that all rely on The same biological mechanism, although the accumulated substances differ from disease to disease* In an interview with the Hidan website, Beitan explains that the atmosphere today is that only drugs that improve an existing process receive funding due to the cuts, and not even a pharmaceutical company takes a risk on developing new approaches

A group of about 30 researchers from six different research groups at the University of California at Los Angeles (UCLA) and together with members of over 20 university groups from other universities in the USA, Germany, Italy, France, Portugal, Brazil and Israel, jointly developed a drug that attacks the The mechanism of amyloid accumulation, a mechanism that underlies many diseases. now they are Asking to raise 2 million dollars on the crowdfunding site INDIGOGO, to a company that will conduct clinical trials of the drug on patients with these diseases.

The group is headed by Prof. Gal Beitan from UCLA, who explains in an interview to the website that if it succeeds in carrying out what it has planned, it may cure or alleviate the condition of patients with more than 30 incurable diseases, including Alzheimer's, Parkinson's, Hantikgenton, Lou Gehrig (ALS), type 2 diabetes, and many diseases in which the same biological mechanism is involved - the accumulation of amyloids. In addition, the accumulation of amyloids is created as a side effect of spinal injuries and even of AIDS.

According to Beitan, who has been researching degenerative diseases for about 15 years, in animal models simulating seven of these diseases, the drug was able to have an effect without side effects.

The basic research was funded by foundations and government grants that support research into diseases such as Alzheimer's, Parkinson's and ALS, but a significant amount is still needed to start clinical trials.
According to Alzheimer's Association data, morbidity from the disease is the sixth leading cause of death in the United States, and while the five diseases at the top of the list have seen a decrease in the death rate (including breast cancer, prostate cancer, heart disease, stroke and AIDS, the number of Alzheimer's victims recorded an increase of 68% in the years 2000- 2010. In fact, new studies show that the number of causes of death associated with Alzheimer's disease is much greater than previously thought and it is possible that it is already the number 3 cause of death. The factor that makes it possible to treat all these diseases is called a "molecular tweezer". The challenge is that the molecular tweezer works in a way It is different from any drug that has been developed so far and therefore it is objectionable by the pharmaceutical companies.
"For the purpose of conducting the clinical trials, a company was established Clear Therapeutics. The company exists but is not yet funded."

The knowledge site: In the explanations it is written that it will be difficult to finance this type of research in orphan diseases through the usual means of government grants, philanthropic funds or pharmaceutical companies. Why actually? Is it because it is interdisciplinary research? Does it conflict with the interests of this or that pharmaceutical company?

Prof. Beitan: "The answer consists of several factors: First, the US economy has been in crisis since 2008. The NIH's research has stagnated since then, which means that the research budgets are actually constantly small, both because the expenses are constantly increasing and also because the budget goes mostly to funding Existing studies and less for new studies. If before the crisis about 25% of the proposals were financed, today about 10% of the proposals are financed. In such a situation, psychological pressure is created on the scientific committees that review the proposals and everyone is just looking for something to reject the proposal."

"In addition, there is heavy pressure on the associations, whose budgets have also decreased greatly in recent years. There are a lot of news and articles in the American media about the fact that scientific and medical research in America is in crisis. What also happens as a result is that research that expands what we know about a certain disease is considered more worthwhile, because each answer will expand the information. On the other hand, research that tries to create a new drug or treatment is considered high-risk because if the drug or treatment does not work, the money will go down the drain. When there is relatively little money, people do not want to take risks. If in the past in our situation it was relatively easy to finance a start-up, today investors are only willing to enter when there are already first results in humans."

"Secondly, the mechanism by which our drug works is unique. Almost all drugs are based on the principle of a small molecule that binds to the binding site of an enzyme or receptor and thus blocks a certain biological activity. The specificity of the binding is based on the unique three-dimensional structure of the enzyme or receptor, and the fit of a small molecule to the binding site like a key to a lock. In the case of the diseases for which our medicine is intended, what causes the disease is small and very toxic clusters of certain proteins - in each disease a different protein - whose structure is very unstable and changes all the time.
These variable constructs do not have a defined binding site. Along with this, many studies show that there are certain molecular interactions that are common to the creation of these structures. These are interactions that can exist in any protein. But the special thing in this case is that, unlike normal proteins, whose structure has been shaped by millions of years of evolution and therefore their interactions are based on very high compatibility and strong forces, in the toxic clusters the interactions are much weaker. These clusters were not supposed to exist normally. Evolution has done a great deal to prevent their formation. But at the ages when these diseases break out, which are usually above the reproductive age, the evolutionary pressure no longer exists. Our drug blocks these particular interactions very gently. The link is relatively weak and breaks and renews many times a second. Its power is sufficient to prevent the creation of the toxic structures, but not to interfere with the activity of normal proteins."

"This mechanism is revolutionary and goes against the conventional wisdom that a drug must not bind to proteins that are not its target. That's why we encounter a lot of skepticism and the difficulty of getting the necessary funding to get to clinical research. We received many relatively small research grants that allowed us to get to where we are. With their help, we have so far shown the effectiveness of the drug in seven different animal models, including fish, mice, and rats. In addition, we have shown that there is a high safety window in mice, so we are asking for the public's support so that we can do the necessary experiments to start clinical trials."

What is your target amount?
"The goal is, as we mentioned on the fundraising page, two million dollars. We believe that this amount will be able to bring us to the start of clinical trials."

Do you have a connection with the Alzheimer researcher groups in Israel (in Tel Aviv there are over 100 researchers conducting research related to the disease according to the last figure I heard)?

"I have contact with a number of researchers in Israel, but not necessarily in the direction of Alzheimer's. I currently have active collaborations with Raz Yelink from Ben-Gurion University and with Dani Segal and Shosh Bar-Non from Tel-Aviv University. In recent years, I have given lectures twice at the Alzheimer's conference of Tel Aviv University, which is organized every year by Amos Korchin and Danny Michaelson, and also at the various universities, including Tel Aviv, Bar-Ilan, Jerusalem, and Ben-Gurion."