CAMBRIDGE, Mass.—Idera Pharmaceuticals, a clinical-stage biopharmaceutical company focused on developing nucleic acid therapeutics for patients with rare and serious diseases, is planning to develop a drug to treat boys with Duchenne muscular dystrophy (DMD). It could be a major breakthrough for a disease that is debilitating and often fatal.
The company will enter a partnership with Parent Project Muscular Dystrophy (PPMD), the largest and most comprehensive nonprofit organization in the U.S. focused on finding a cure for DMD, to conduct early-stage research into a drug that would slow the deterioration of muscles caused by the deadly disease. The drug could be used with in conjunction other drugs likely to be approved to work in boys with any underlying genetic mutations.
DMD is caused by genetic mutations that result in a lack of a protein called dystrophin that is needed for muscle formation. As a recessive X-linked form of muscular dystrophy, the disease overwhelmingly affects male children. The muscles start degenerating because of inflammation. The rare, fatal neuromuscular disorder is characterized by progressive muscle weakness, increasing disability limiting activities of daily living, pulmonary and cardiac dysfunction and death typically before age 30. It affects approximately 15,000 to 20,000 patients in the United States.
Because of compromised cellular membranes, dying and damaged muscle cells release self-RNAs and other molecules that are recognized by the body’s innate immune system as damage-associated molecular patterns (DAMPs). DAMPs stimulate Toll-like receptor (TLR)-mediated signaling pathways that trigger an inflammatory response. This TLR-mediated inflammatory response is believed to cause additional muscle cell damage, propagating a cycle of tissue damage that contributes to disease progression. TLRs represent novel targets in DMD upstream of other traditional inflammatory targets.
Idera hopes to create a drug to stop inflammation by blocking TLR, an approach that looks promising according to animal studies. Idera and PPMD plan to work together to conduct preclinical studies and develop a clinical development strategy for an investigational TLR antagonist candidate. In previous preclinical studies in models of DMD, treatment with a TLR antagonist candidate led to a reduction in disease-associated markers of inflammation and improved muscle function.
“We look forward to partnering with Idera Pharmaceuticals, a leader in the development of nucleic acid therapeutics for rare diseases, to advance a novel approach to controlling muscle inflammation with the potential to treat all patients, regardless of their genetic mutation,” said Pat Furlong, founding president and CEO of PPMD. “One of our organization’s primary objectives is to advance potential treatments, so that all people with Duchenne have an opportunity to live longer and fuller lives. For 20 years, we have done whatever we can to support new and promising technologies. PPMD looks forward to working with Idera on this new area of biology to advance treatments applicable to all patients.”
“We are very pleased to work with PPMD on advancing the potential application of TLR antagonism to address the underlying inflammation that propagates disease progression in Duchenne. PPMD brings decades of experience working with families affected by Duchenne, as well as close ties with scientists and clinicians working in the field worldwide,” said Dr. Sudhir Agrawal, CEO of Idera Pharmaceuticals. “We look forward to collaborating with PPMD and researchers from Children’s National Health System to conduct preclinical studies to inform a clinical development strategy.”
“Over the last five years, we have demonstrated in preclinical studies that TLRs play a critical role in triggering inflammation in neuromuscular diseases such as Duchenne. Based on this research, we believe there is a clear scientific rationale for the evaluation of TLR antagonism as a potential treatment approach,” said Dr. Kanneboyina Nagaraju, professor of integrative systems biology and pediatrics at the George Washington University School of Medicine and Health Sciences and Children’s National Health System.
Independent research published by investigators from Children’s National Health System in Washington, D.C., has demonstrated the role of TLRs in the pathogenesis of DMD. Additional preclinical research published by investigators from Children’s National Health System and Idera showed that inhibition of TLR activity improved disease-associated measures in Duchenne models.