Isis Pharmaceuticals has initiated a study for ISIS-DMPKRx in patients with Myotonic Dystrophy Type 1 (DM1).  DM1 is a rare genetic neuromuscular disease caused by the production of toxic dystrophia myotonica-protein kinase (DMPK) RNA in cells.  ISIS-DMPKRx is specifically designed to reduce toxic DMPK RNA.

"The Myotonic Dystrophy Foundation is pleased that Isis is advancing to the next phase of clinical trials for ISIS-DMPKRx," said Molly White, executive director of the Myotonic Dystrophy Foundation.  "Myotonic Dystrophy, the most common form of muscular dystrophy, is a devastating disease with no therapeutic option.  Myotonic dystrophy research has accelerated significantly in the last 10 years, helping bring about the innovative science behind ISIS-DMPKRx, a drug that specifically targets the genetic defect that causes myotonic dystrophy type 1.  We applaud Isis for investing in and leading drug development efforts for myotonic dystrophy type 1, and we appreciate the commitment Isis Pharmaceuticals has made to improve the lives of patients in our community."

"We have an innovative and productive partnership with Biogen Idec in developing drugs to treat severe and rare diseases, like DM1.  In just under two and a half years, we have been able to discover and complete early development on ISIS-DMPKRx, which includes completing a phase 1 single ascending-dose study in healthy volunteers.  Today we advance this programme into patients," said B. Lynne Parshall, chief operating officer at Isis.  "The speed at which we have advanced ISIS-DMPKRx highlights the productive and collaborative nature of our partnership."

DM1 is a rare genetic neuromuscular disease primarily characterised by progressive muscle atrophy, weakness and myotonia.  DM1 is the most common form of muscular dystrophy in adults and affects approximately 150,000 patients in the United States, Europe and Japan. Patients with DM1 have a genetic defect in their DMPK gene in which a sequence of three nucleotides repeats extensively, creating an abnormally long RNA, which becomes toxic as it accumulates in the nucleus of cells and prevents the production of proteins needed for normal cellular function. The number of triplet repeats increases from one generation to the next, resulting in the possibility of more severe disease in each subsequent generation.  There are currently no disease-modifying therapies that address the disease.

"Myotonic dystrophy represents an ideal opportunity for antisense as the disease-causing gene produces a toxic RNA, which accumulates within cells, including muscle, and is not accessible by traditional therapeutic approaches.  ISIS-DMPKRx has the potential to address the underlying genetic defect that causes DM1.  This study is important as it is the first study in which we will be observing the effects of our drug in patients with myotonic dystrophy, and it is the first study in which we are targeting a toxic RNA," said C. Frank Bennett, senior vice president of research at Isis.  "ISIS-DMPKRx is our third generation 2.5 drug to enter clinical development.  In this study we plan to evaluate and determine the approximate therapeutic dose of an antisense drug needed to affect the concentration of a target in muscle tissue."

The phase 1/2 study is a randomised, placebo-controlled, dose-escalation study evaluating the safety and tolerability of ISIS-DMPKRx.  The six-week study will evaluate multiple ascending doses of ISIS-DMPKRx in approximately 36 patients with DM1.