MG is an autoimmune disease thought to interrupt the transmission of nerve impulses to muscles at the neuromuscular junction, or the location where nerve cells connect with the muscles they control. In MG an autoimmune response attacks acetylcholine receptors (AChR), which blocks nerve impulses and muscle stimulation via the neurotransmitter acetylcholine. As a result of this self attack, MG patients experience chronic fatigue, weakness, double vision and in some cases respiratory distress.
The Myasthenia Gravis Foundation of America estimates that up to 60,000 people in the United States may have MG. Approximately 12%-16% of those afflicted experience potentially fatal myasthenic crisis due to progressive weakness of the respiratory muscles, which is exacerbated by physical activity.
Current Treatments for MG
No disease-modifying therapies are currently approved for MG. Existing treatment options have limited efficacy, are often associated with significant side effects and only address the symptoms of MG. Therapies include anticholinesterase drugs, such as neostigmine and pyridostimine, which address chronic fatigue and weakness; and off-label use of chemotherapeutic agents and broad-based immunosuppressants such as corticosterods. Although thymectomy, or surgical removal of the thymus gland, is performed in more severe cases it may produce remission.
About BHT-3034
BHT-3034 is a plasmid encoding the AChR designed to induce tolerance and improve the clinical outcomes in patients with MG. This product candidate is currently in preclinical studies, where it has already shown positive results in an experimental autoimmune MG model (EAMG), and is expected to enter IND-enabling studies in 2008.
Preclinical data
The efficacy of an animal-model equivalent of BHT-3034 (rBHT-3034) was demonstrated in rodents using the EAMG model. Either rBHT-3034 or saline was administered intramuscularly once per week and data was collected on several parameters of EAMG severity in already established disease. rBHT-3034 showed favorable results versus saline injections as follows:
