Sunday Morning Science

It is a LAMposium tradition that on Sunday morning a brief summary of the scientific portions of LAMposium is given to the LAM patients, family, and friends. This year the challenge of translating the science into terms for the lay person fell to Dr. Greg Downey, the Basic Science Chair for The LAM Foundation International Research Conference. In his introduction, Dr. Downey commented that this year's conference included some evolving and developing areas of science, some of which had no prior exposure to LAM.

Dr. Downey divided his presentation into several categories: Signaling, Lymphatics, Hormones, Cancer and Metastasis, Origin of the LAM Cell, and Clinicals (biomarkers, trial design for rare diseases). What follows are just some of the conference highlights.

SIGNALING

Major inroads have been made into understanding how LAM and Tuberous Sclerosis cause disease. This opens the potential for finding existing drugs that might be used to treat LAM. Data from the CAST trial in Cincinnati showed that the effects of Sirolimus might be reversed once the drug was stopped. It may be that the LAM cells are still there and are not being killed.

Reports were made at the conference about several different drug categories that when added to Sirolimus might prevent this reverse and actually kill the LAM cells. Prolactin, a reproductive hormone in women might affect the progression of LAM and therefore be a potential therapeutic target.

Presentations were made on new technologies that could be applied to the study of LAM signaling pathways and the rapid screening of potential therapeutic compounds and their interactions with the LAM pathways. This could dramatically speed up the examination of drugs and their effects on LAM.

LYMPHATICS

Study of the lymphatic system really only started about 10-12 years ago. This is really the first year that scientists from this field and now looking at potential applications in the field of LAM.

Technology is now available that allows for the study of the lymphatic system in living persons. This opens up a whole new area in studying the development and progression of LAM.

HORMONES

There are almost certainly female hormones involved in the development of LAM. It is now known that there are two types of estrogen receptors that may have different effects. Medications are now being developed that could selectively inhibit one or the other of these receptors and might be of interest in the treatment of LAM.

A presentation was made that showed that estrogen might be preventing a process that would result in the death of LAM cells.

ORIGIN OF THE LAM CELL

A group from Japan has done some microscopic studies of the uterus that found found the presence of LAM cells. Additional studies looking for the same cells in the uteri of women without LAM are now underway (the negative controls).

BIOMARKERS

Results from the studies on the use of VEGF-D as a biomarker were presented which showed that a VEGF-D at a specific level along with a high resolution CT and other compatible symptoms is diagnostic for both sporadic and TSC-LAM. Laboratory certifications will be needed to minimize laboratory test variation and standardize the testing procedure.

Research continues for additional biomarkers that could be used for tracking the effects of therapies in clinical trials.

CLINICAL TRIALS FOR RARE DISEASES

Due to the small number of women with LAM, it can be very difficult to set up and conduct clinical trials. In order to speed up the ability to conduct clinical trials for LAM, alternative methods are being discussed. One is the N=1 trial in which a single patient goes on and off the trial drug several times and acts as their own control. This needs much more discussion and study to make sure that stastically powerful trials can be conducted.

Dr. Downey emphasized the need to plan, finish, and analyze clinical trials correctly. It can be difficult for those of us wanting fast results but is necessary for obtaining reliable results that will be acceptable to the scientific and clinical community.


Mary Harbaugh