New Class of Drugs May Eventually Treat Over 30 Diseases

Compounds that prevent protein aggregation may lead to therapy for conditions such as cancer and diabetes.

The development of compounds that can safely block harmful protein aggregation indicate a new class of drugs may soon treat over 30 conditions such cancer, diabetes, spinal cord injury, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis (ALS).

The findings of a study presented at the recent American Society for Biochemistry and Molecular Biology annual meeting evaluated proteins involved in nearly all cellular processes, which can aggregate into toxic plaques that lead to disease when cell machinery fails to eliminate old proteins.

"Diseases caused by protein aggregation affect millions of people around the world," study presenter Gal Bitan, PhD, said in a press release. "We hope that the new compounds will provide therapy for diseases caused by protein aggregation, many of which have no treatment at all."

These compounds, dubbed molecular tweezers due to the way it wraps around lysine amino acid chains that comprise most proteins, are unique in the ability to attack only aggregated proteins while leaving healthy proteins alone, the study noted.

The researchers used a fundamentally different approach to develop the molecular tweezers than what is typically used to develop new drugs, which typically involve screening large numbers of compounds to evaluate which ones affect a protein involved in a disease.

"We looked at the molecular and atomic interactions of proteins to understand what leads to their abnormal clumping," Dr. Bitan said. "Then, we developed a tailored solution. So unlike many other drugs, we understand how and why our drug works."

The researchers are currently evaluating multiple versions of the tweezers with a slightly different molecular makeup. Among the most promising compounds, CLR01, demonstrated therapeutic benefits in 2 rodent models of Alzheimer's disease, 2 fish and 1 mouse model of Parkinson's disease, 1 fish model of spinal cord injury, and a mouse model of the rare disease familial amyloidotic polyneuropathy.

"Our data suggest that CLR01, or a derivative thereof, may become a drug for a number of diseases that involve protein aggregation," Dr. Bitan noted. "We also found a high safety window for CLR01."

During safety testing, rodents who received a daily dose of CLR01 that is 250 times greater than the therapeutic dose for a month showed no behavioral or physiological signs of damage. Additionally, the blood cholesterol in mice dropped 40%, which indicates a potential positive side effect of CLR01.

Researchers plan to continue the evaluation of CLR01 for the treatment of various diseases, with hopes that improvements to the compound would lead to CLR01 being administered in a pill or capsule instead of an injection.