Currently, there are five FDA-approved drugs for Alzheimer’s disease (AD), all of which treat the symptoms, but not the cause of the disease. The beneficial effects of these drugs are mild and temporary.

Parkinson’s disease (PD) patients currently are treated mainly by dopamine-replacement therapy, which initially is effective in treating the major symptoms – tremor and rigidity, but the effects wear off after a while. Unfortunately, the treatment causes major side effects, such as involuntary movement, which may become more debilitating than the disease itself. In addition, because it does not treat the cause of the disease, dopamine-replacement therapy has no effect on “non-dopaminergic” symptoms of PD, including falling, freezing, insomnia, chronic constipation, loss of sense of smell, depression, and dementia, each which afflicts a large percentage of people with the disease.

Alzheimer’s and Parkinson’s diseases are the two most prevalent neurodegenerative diseases, together affecting over 55 millions of people worldwide. Due to the rapid aging of the population, both diseases threaten to become epidemics in the 21st century. The life span of patients with AD is 8 years on average and may extend up to 20 years from the onset of symptoms. During the long years of illness, the patients, families, caretakers, and society in general suffer grave emotional and financial duress.

Alzheimer’s statistics: Current cost estimates of care for patients with AD in the US are ~$150 billion a year. More than 35 million people worldwide have AD. This number is projected to nearly double every 20 years, to 66 million in 2030, and 115 million in 2050.

Parkinson’s statistics: Current global estimates of PD are 22 million. Similar to AD, the major risk factor for PD is age. However, unlike AD, which very rarely afflicts people under age 60, PD strikes people in their 20’s and 30’s who struggle to work and raise families.

Common pathologic mechanism: Both AD and PD are caused by abnormal protein aggregation and both diseases have no cure. In each disease, the natural control systems of the brain fail to manage a particular protein. The protein then self-associates into toxic aggregates that disrupt the normal function of brain cells and eventually and kill them. Treatment and prevention of these diseases is a major, unmet, public health challenge.

Our solution is a unique, rational approach to drug design. Using this approach, Clear Therapeutics has discovered novel compounds that block the self-association of the proteins that cause AD and PD and rescue the normal function of brain cells. Initial preclinical experiments show high efficacy in animal models without signs of negative side effects.

The unique Clear approach: Traditional drug discovery is based on high-throughput screening of thousands-to-millions of compounds. Despite tremendous efforts, this approach has not been successful for AD and PD because aggregated proteins are very different from traditional drug targets.

Clear’s discoveries are the result of a rational design paradigm developed by Dr. Gal Bitan in the Department of Neurology at UCLA. Since 1999, Dr. Bitan has been studying a protein called beta-amyloid, which self-associates into neurotoxic aggregates in the brain and causes AD. Dr. Bitan used his intimate, detailed knowledge of the molecular interactions that control beta-amyloid aggregation to discover novel compounds that act through a unique, proprietary mechanism and do not suffer from the shortcomings and side effects that have plagued competing approaches.

The unique mechanism by which the compounds discovered by Dr. Bitan work enables targeting not only beta-amyloid, but also a variety of proteins that self-associate into toxic aggregates and cause more than 30 different diseases, commonly called “amyloidoses,” including Parkinson’s disease, dialysis-related amyloidosis, type 2 diabetes, systemic amyloidosis, and others.

Clear has licensed the technology from UCLA and is developing novel therapeutics for Alzheimer’s disease, Parkinson’s disease, and other amyloidoses.