Breakthrough Treatment for Degenerative Diseases (BTDD) is a project led by Dr. Gal Bitan, Associate Professor of Neurology at UCLA, and conducted in collaboration with many laboratories worldwide. The goal of the project is to develop novel drugs for diseases caused by abnormal protein aggregation, including Alzheimer’s disease, Parkinson’s disease and many more. The drugs are based on compounds called Molecular Tweezers that have been invented by Professors Frank-Gerrit Klärner and Thomas Schrader at the University of Duisburg-Essen, Germany, and their potential for prevention of abnormal protein aggregation was discovered by Dr. Bitan. The initial collaboration among Professors Klärner, Schrader and Bitan has developed into a project including over 30 laboratories around the world.
The current research and development are conducted in the academic laboratories of Dr. Bitan and the different collaborators with funding from government and foundation grants, public support, and philanthropy. Future development likely will require involvement of the biotechnology and pharmaceutical industry.
Gal Bitan (center) visiting Thomas Schrader (right) and Frank Klärner (left) at the University of Duisburg-Essen, 2016.
There are over 30 diseases caused by abnormal protein aggregation (they are called amyloidoses or proteinopathies). In addition, abnormal protein aggregation is involved in pathologic conditions, such as viral infection, cancer, spinal-cord injury, traumatic brain injury, and others (see our comprehensive list of diseases and conditions). In each of these diseases, the molecules of one or more proteins in our body lose their normal structure and clump together (aggregate). There are many types of clumps that can be divided into two classes – the initial one is small clumps called oligomers. Oligomers contain only a few molecules bound together by weak forces, but they are the most toxic kind of clumps. First, they shut down the function of cells and later they kill the cells. The second class is large clumps containing thousands of molecules. They are so large that they become insoluble in the bodily fluids and turn into “deposits” that can be observed by pathologists in the affected tissues. Such deposits include the amyloid plaques and neurofibrillary tangles in Alzheimer’s disease and the Lewy bodies in Parkinson’s disease. In general, this form of proteins is called amyloid.
The molecular tweezers work in a unique way that is not shared by compounds tested previously in clinical trials or laboratory experiments. In fact, they are the first case in which the mechanism of action of the compounds is well understood. The molecular tweezers have been found to prevent the abnormal aggregation of many proteins, block their toxicity, and treat the associated diseases in several scientific models, including models of Alzheimer’s disease, Parkinson’s disease, and Familial Amyloidotic Polyneuropathy. They also were found to prevent the death of nerve cells in a scientific model of spinal cord injury. Recently, a new function was found for molecular tweezers – destruction of viral membranes, including those of the HIV, hepatitis C, and herpes viruses.
To learn more about the results in these different models, visit the individual team members’ pages, check out our News, and read our scientific publications. Our project has two main goals: To advance our understanding of the mechanistic underpinning of molecular tweezers’ therapeutic effects, and to turn the molecular tweezers into drugs against all of these diseases and pathological conditions. We are testing the molecular tweezers against more diseases, are using sophisticated techniques to decipher the molecular mechanisms by which they work, and are conducting the necessary experiments required by the FDA for initiation of clinical trials. The latter item is particularly expensive and we are actively exploring every option for obtaining the necessary funding, including grants, philanthropy, and pharmaceutical industry connections. We are very grateful to all our donors for sharing our vision of bringing relief to millions of people suffering from these diseases.