Metabolic Disorders

Metabolic disorders such as diabetes and obesity are an enormous and growing medical challenge in our society. These diseases are among the leading causes of mortality and disability, and their prevalence is increasing at an alarming rate, reaching epidemic proportions. Acceleron is applying its expertise in GDF biology to develop therapies that modulate fat and muscle tissue to treat these diseases.

Type II Diabetes Mellitus

Type 2 Diabetes (T2DM) is a chronic, progressive disease that results from poorly-controlled, elevated blood glucose levels. The disease may be initially clinically silent, but progression is insidious, leading to numerous clinical consequences and premature death. T2DM is currently one of the most pressing public health concerns:

Approximately 15 million people in the U.S. have been diagnosed with Type 2 Diabetes
Type 2 Diabetes is the sixth leading cause of death in the U.S.
Total cost of diabetes in the U.S. is over $132 billion a year

Disease Severity Lies in the Development of Complications

The severity of T2DM lies in the development of complications from constantly elevated, circulating glucose. At high levels, glucose is effectively “toxic”, and through a variety of mechanisms, damages the cardiovascular system among others, leading to life-threatening complications:

Underlying Pathology of Type II Diabetes

Proper maintenance of glucose levels requires the coordination of insulin production and the consequent uptake of glucose from insulin stimulation. Dysfunction of these mechanisms, characterize the disease pathology of Type II Diabetes:

Progressive loss of islet cell function and decreased ability to produce insulin
Increasing insulin resistance by muscle tissue and impaired glucose metabolism

Accordingly, exercise and physical activity, in addition to pharmacotherapy, are often recommended to drive tissue demand for glucose.

Tremendous Need for Novel Approach to Treating Type II Diabetes

Because of the progressive nature of T2DM, current treatment approaches have limited therapeutic utility. Patients require increasingly higher (often intolerable) doses and poly-pharmacy to control blood glucose. Ultimately, the waning efficacy of these agents, compounded by poor patient compliance, results in continued disease progression and the onset of serious disease complications.

Acceleron is developing therapies that modulate the growth of muscle and adipose tissue to treat Type 2 Diabetes. Increasing lean muscle mass can improve body composition, potentially increasing insulin sensitivity and glucose demand.

Obesity

The prevalence of obesity has increased at an alarming rate to epidemic proportions over the last 20 years. As a result, obesity has emerged as a major public health concern, given the serious impact and complexity in treatment of the disease.

The World Health Organization (WHO) defines obesity as a body mass index (BMI) greater than or equal to 30, and overweight as a BMI between 25 and 30.

Approximately 127 million adults in the U.S. are overweight; 60 million are obese; and 9 million are severely obese
14-17% of children and adolescents are obese
Obesity is a major risk factor for the development of several complications including:

The health costs associated with obesity in the U.S. are ~$177 billion per year
Gender, race, and economic status are all major risk factors for obesity

Complex disease process

The deposition, distribution, and growth of fat cells in the body are regulated by a host of signals and targets. An imbalance in signals that direct the accumulation of fat, from both genetic and behavioral factors, results in the overproduction of fat tissue.

Tremendous need for safe, effective treatment for obesity

Despite the growing recognition that obesity is a disease and not purely a lifestyle condition, few safe and effective treatments have been developed. For many patients, it is only the combination of pharmacological or surgical intervention with lifestyle modification that can adequately treat obesity. Acceleron is developing therapies that target the accumulation and proliferation of adipose tissue for the treatment of obesity.