Tuberous sclerosis complex (TSC) is a genetic disorder. It is passed down from parents to their children. The genes (DNA) associated with TSC are involved in controlling cell growth. Patients with TSC develop tumors in multiple organs in their body, including the brain, heart, lungs, kidneys, eyes, and skin.

The changes found in the genes of TSC patients cause skin cells to be made at a faster rate than they can be sloughed off the surface. This overproduction of skin cells results in the formation of tumors on the face (facial angiofibromas). Facial angiofibromas appear in early childhood in up to 80% of people with TSC. The angiofibromas appear as red or pink bumps distributed over the middle of the face, especially on the folds of the nose, the cheeks, and the chin. The bumps look like acne and cause a lot of distress and embarrassment to people with TSC. Currently there is no effective way to prevent or permanently remove them.

Rapamycin is a naturally occurring substance produced by a bacterium named Streptomyces. These bacteria produce over two-thirds of all the antibiotics used by humans that are of natural origin. Rapamycin works in a similar manner to the TSC gene products and, in theory, it can replace the action of the TSC genes in people with TSC, thus preventing the uncontrolled cell growth. Rapamycin taken by mouth has side effects that limit its use to treat the skin findings of TSC. Side effects include mouth sores, increased cholesterol, blood clotting problems, acne, increased risk of infections, and poor wound healing.

Rapamycin is very small and is able to pass through the top layers of the skin to reach the lower layers where the cells are growing too fast. Applied to the skin surface like this, rapamycin is able to reach the deep skin cells without being absorbed by the body and causing the side effects seen when it is taken by mouth.

This project involves testing a new formula containing rapamycin that can be applied to the skin surface. The clinical trial will involve 10 different TSC centers throughout the country and will include up to 200 TSC patients.

The primary goal of this study is to see if the new formula reduces the appearance of facial angiofibromas in patients with TSC. The secondary goal of this study is to confirm the safety of the formula.

During the first year of the project, laboratory studies will occur to test the purity, bioavailability, stability, and lack of irritation of the new drug. The research protocol with be reviewed by each site where study subjects will be enrolled and individual study sites will be trained on trial procedures and protocols.

During the second and third years of the project, 200 subjects will be enrolled into the study. Study subjects will apply either a polymer-based skin coating containing rapamycin or the polymer coating alone nightly to their angiofibromas. Each subject will use the investigational product for a total of 6 months. Photographs will be taken monthly and rapamycin blood levels will be drawn to confirm lack of absorption.

Once the study is finished, the photographs will be reviewed by a dermatologist. The dermatologist will assess each photograph's appearance and will compare photographs taken at study visit #1 (before treatment) to those from study visit #7 (after finishing treatment). They will also rank each study subject's appearance on a scale and compare their "severity" from before and after treatment.