Can tamoxifen help patients with Lou Gehrig’s disease?

Prompted by his observation of an ALS patient who subsequently developed breast cancer, a UW Medical School researcher has found that the drug tamoxifen significantly delayed movement problems and prolonged survival in a group of 40 mice with an ALS-like disease.

While the animal study is small, the findings have prompted neurologist UW–Madison Benjamin Brooks to begin a study of tamoxifen’s impact on human patients with ALS (amyotrophic lateral sclerosis, also known as “Lou Gehrig’s disease”).

Brooks, professor of neurology and a specialist in ALS, presents his research findings Tuesday at the annual meeting of the Society for Neuroscience in San Diego.

ALS is a chronic, progressive disease affecting the nerve cells that control voluntary movement. It is not curable and is usually fatal.

Tamoxifen is commonly prescribed for women with breast cancer, and was approved by the Food and Drug Administration in 1998 for healthy women at high risk of the disease. The drug works by blocking estrogen from entering cancer cells and thus reduces or eliminates the cells’ ability to grow and spread. It is being studied now as a potential treatment for brain tumors as well.

In 1997, one of Brooks’ ALS patients was diagnosed with breast cancer and began treatment with tamoxifen. Over the next 42 months, Brooks noted that the woman’s muscle strength stabilized instead of deteriorating, which would be expected as ALS progresses. Intrigued by the observation, Brooks found recent studies suggesting that tamoxifen may inhibit protein kinase C (PKC), a group of enzymes involved in several cellular processes. PKC is found in many body tissues and is thought to be involved in nerve cells’ ability to send signals to each other.

“Evidence is emerging that tamoxifen affects the nervous system in several ways that are just beginning to be understood,” says Brooks. “The area we’re interested in concerns tamoxifen’s possible disruption of PKC, which is a different mode of action from its disruption of estrogen activity. The hope is that a drug that blocks PKC might be helpful in several disorders.”

In the study, researchers used mice infected with a virus known to create the nerve cell degeneration seen in ALS. Typically, the mice begin showing signs of paralysis at 28 days after infection and die eight days later. When given tamoxifen, the initial symptoms of paralysis were delayed eight days (22 percent) and the mice died, on average, at 48 days after infection (25 percent longer).

Brooks said although the study is very preliminary, he finds “exciting potential” in the emerging evidence that there may be a viral link to diseases such as ALS and even schizophrenia and that tamoxifen might prove a useful treatment. His research group is now conducting tests of tamoxifen in ALS patients to see if it helps sustain their muscle strength. He is also doing more animal studies to uncover how the drug might produce its effects.

“There is only one FDA-approved treatment for ALS right now,” says Brooks, who has been treating ALS patients for 18 years. “All of us in the field are eager to find a medication that might sustain quality of life longer, until a cure is found. We have a long way to go, but I’m very excited at what we have seen with tamoxifen thus far.”

Tamoxifen does have side effects, which include an increased risk of endometrial cancer, deep vein thrombosis, and blood clots in the lungs.

The patient whose medical history inspired Brooks’ study now lives outside the area.