Case Number 096012 - Item Number 239 - Treatment for Cystic Fibrosis & Other Conditions

Contact: Ellen Monson
Phone: 513-558-5274

Description:  Defective chloride transport causes cystic fibrosis (CF), which manifests as mucoviscidosis and pancreatic insufficiency in afflicted patients. Abnormally deficient chloride transport results leads to blockage of the bronchioles in the lung, leading to emphysema and localized atelectasis. Transport duct blockage by mucous in the pancreas results in digestive enzyme insufficiency in the small intestine, leaving patients with poor nutritional status. A number of research approaches have been undertaken toward the development of a treatment for CF. Palliation or amelioration of the disease condition could be accomplished through reconstitution of normal chloride channel function or activation of chloride transport through alternate channel activation.
The present invention describes a pharmacological activator of non-CFTR chloride channels such as members of the ClC channel family. These channels are widely distributed in the body, and serve functions in secretion and absorption of fluid and maintenance of normal nerve, muscle, and kidney function. The pharmaceutical agent activates ClC chloride channels when applied directly to the surface of the tissue, such as lung, resulting in activation of the channels and increased chloride transport. This approach represents a novel therapeutic modality for the treatment of CF.
The subject matter of the patent is a method of treating a pathology having symptoms caused by inadequate chloride transport by defective ClC-2G chloride channels, comprising administering to an individual in need of such treatment 1) a condensation agent and 2) an amine in amounts effective to activate chloride transport by inactivating charged groups on amino acid residues of said channels, thereby counteracting said symptoms.
This patented method has several key potential benefits. The compound can be delivered using standard treatment techniques for the delivery of therapeutics to the lung. Unlike many traditional systemic therapies, the pharmacological agent is delivered and acts exogenously, and is expected to be relatively non-toxic.
This approach to the treatment of CF employs a traditional pharmaceutical application that has much higher likelihood of success than more complicated gene therapy based approaches. Most current research focuses on treatments for infection and inflammation, as well as gene replacement. The Cystic Fibrosis Foundation reports that many physicians and researchers believe that a successful chloride-releasing therapy would be of tremendous benefit to CF patients. This technology's straight-forward approach, coupled with the expected favorable safety and toxicity profile, present a licensing opportunity with substantial potential to improve the lives of CF patients.

Issued, U.S. Patent No. 6,015,828, January 18, 2000 entitled "Chemical modification of chloride channels as a treatment for cystic fibrosis and other diseases."