Nucleic acids are highly promising candidates for the treatment of rare diseases. It is expected that not every nucleic acid approach will result in a therapeutic effect for every rare disease. In addition, many rare diseases are multi-system diseases which impact more than one organ or physiological process, so treatment using a singular therapeutic or delivery regimen may not be successful. Further, the efficient and cell-specific delivery of oligonucleotide therapeutics remains a challenge for clinical progress.
Successful treatment of rare diseases may require a comprehensive approach over the course of care that employs multiple therapeutics, each with a specific biological target, dose, and delivery mechanism.
Marina Biotech's unique ability to develop both single- and double-stranded oligonucleotide constructs and to deliver these therapeutics with fundamentally different modalities and molecules may provide the greatest chance for clinical success.
Familial Adenomatous Polyposis
Familial Adenomatous Polyposis (FAP) is a rare hereditary disease affecting approximately 1:10,000 persons worldwide. In FAP, a mutation in the Adenomatous Polyposis Coli (APC) gene causes dysregulation and accumulation of β-catenin. This results in the appearance of numerous colon polyps during early adolescence with potential for rapid disease progression and a near 100% risk of colon cancer if untreated. Surgical intervention is currently the only available treatment.
Marina Biotech’s clinical drug product, CEQ508, targets the β-catenin oncogene via RNAi and has the potential to be a first-in-class therapeutic for the treatment of FAP.
CEQ508 is being developed as an orally administered treatment to specifically target and reduce the levels of β-catenin in the epithelial cells of the small and large intestine, and is expected to represent a significant breakthrough in the treatment of FAP. Currently, nonsteroidal anti-inflammatory drugs are prescribed in combination with standard of care practices, i.e. surgery. For many patients, complete colectomy (surgical removal of the entire large intestine), which is usually performed in the late teenage years or early twenties, remains the primary treatment. However, surgical intervention is not curative as the risk of polyps forming in the remaining portions of the intestinal tract and in the small intestine remains after colectomy.
CEQ508 is the first drug candidate in a novel class of therapeutic agents employing our Transkingdom RNA™ interference (tkRNAi) platform.
Myotonic dystrophy is a form of muscular dystrophy that affects muscles and many other organs in the body.
Myotonic dystrophy type 1 (DM1) is an autosomal dominant, multi-system disorder that affects both smooth and skeletal muscles and may affect the central nervous system, heart, eyes, and/or endocrine systems. There are three types of DM1 that are distinguished by the severity of disease and age of onset. Mild DM1 is characterized by cataracts and sustained muscle contractions (myotonia). Classic DM1 is characterized by muscle weakness and wasting (atrophy), cataracts, myotonia and abnormalities in the heart's conduction of electrical impulses. Congenital DM1 is characterized by muscle weakness (hypotonia), difficulty breathing, mental retardation and early death.
DM1 is caused by an abnormality in the DMPK gene. Affected individuals have an increased number of copies of a portion of this gene called CTG. The greater the number of repeated copies of CTG, the more severe the disorder. DM1 affects at least 1 in 8,000 people worldwide.
Duchenne muscular dystrophy (DMD) is a rapidly progressive form of muscular dystrophy that occurs primarily in boys. It is caused by a mutation in the DMD gene that can be inherited in families, but it often occurs in people from families without a known family history of the condition.
Individuals who have DMD have progressive loss of muscle function and weakness, which begins in the lower limbs. The DMD gene is the second largest gene to date, which encodes the muscle protein, dystrophin. Boys with Duchenne muscular dystrophy do not make the dystrophin protein in their muscles.
Duchenne muscular dystrophy affects approximately 1 in 3,500 male births worldwide. Because this is an inherited disorder, risks include a family history of Duchenne muscular dystrophy.