What is LAM?

LAM is a lung disease that affects women. The main symptoms are shortness of breath with exertion, fatigue, cough and chest pain. Women with LAM often look completely healthy, but the lungs are full of holes and slowly being destroyed.

About 2/3 of women with LAM experience episodes of collapsed lung(s). Having a lung collapse means hospital admission, painful treatment and sometimes difficult lung surgery. About half the women with LAM also have kidney tumours called angiomyolipoma (AML). Some women have abdominal LAM and others have been diagnosed after bleeding kidney tumours. LAM is progressive, with no treatment or cure. LAM is diagnosed only in women and hits usually in the prime of life.

Continuous supplemental oxygen is often needed and the last option is a single- or double-lung transplant. So far, these options allow for the extension of life only but it is eventually fatal shortening the life span and the quality of life for virtually every woman with the disease. In the past, LAM was often misdiagnosed as asthma or emphysema, but now LAM can be diagnosed more easily from a lung biopsy or a CT-Scan. Women with LAM are still frequently misdiagnosed because many physicians continue to be unaware of this disease. It is important to obtain a correct diagnosis both because of the dangers of inappropriate treatments being applied and because of the steps that can be taken to make life more comfortable for women with LAM.

What causes LAM?

There are two types of LAM: sporadic LAM and LAM associated with another condition called tuberous sclerosis complex (TSC).

The cause of LAM is unknown. But recent research has found that LAM is associated with mutations in the TSC1 and TSC2 genes, the same genes that are associated with tuberous sclerosis. What is known is that LAM cells (an unusual type of smooth muscle cell) invades lung tissue, destroys air sacs and obstructs the airways leading to increasing respiratory impairment.

About LAM

Significant strides have been made in understanding, diagnosing and treating symptoms and complications of LAM in the last 10 years. Still, there is an urgent need to:
  • Increase awareness about LAM in the medical and lay communities;
  • Ensure that women get a proper diagnosis;
  • Dedicate research funding to find a safe and effective treatment for LAM and ultimately, a cure.

Facts About Lymphangioleiomyomatosis (LAM)

  • Symptoms include shortness of breath, collapsed lung, chest pain, cough, or fatigue.
  • Up to 50% of women with LAM have a benign kidney tumour called angiomyolipoma.
  • LAM usually does not appear on an x-ray. A high-resolution CT-Scan of the chest, and often the abdominal area, is required for accurate diagnosis.
  • LAM results in progressive destruction of healthy lung tissue caused by cyst formation and abnormal growth of smooth muscle cells, not usually found in the lungs.
  • Lung capacity progressively declines, resulting in the need for oxygen therapy.
  • Women often go undiagnosed for years, and are frequently misdiagnosed with asthma, bronchitis, or emphysema.
  • The discovery of a genetic link between LAM and tuberous sclerosis (TS) leads scientists to estimate that more than 250,000 women worldwide are unaware they have LAM.
  • As LAM occurs primarily in women, the disease is thought to be hormonally-related.
  • Many doctors think pregnancy accelerates the disease.
  • There is no cure and no treatment that has proven to be effective.

LAM: is it cancer?

What is the thinking behind this statement? According to LAM researchers Dr. Frank McCormack and Dr. Lisa Henske, the term “cancer” defines a spectrum of diseases which have four elements in common: 1) genetic mutations, 2) loss of control of cellular growth and cell survival, 3) movement of abnormal cells to new sites (metastasis) and, 4) tissue destruction. All of these elements are present in LAM:
  1. Genetic mutations: As in cancer, genetic mutations develop in cells. These mutations allow the cell to multiply, move to other locations in the body (metastasis) and resist dying (apotosis). In cancer cells, there are multiple genetic mutations. In LAM, we know that the TSC1 or TSC2 genes are mutated but additional mutations may occur after the initiation of LAM to make the disease more aggressive in some patients. The mutation in the TSC1 or TSC2 gene is involved in a single but critical pathway that controls cell growth, movement, and survival.
  2. Loss of growth control: Tuberous sclerosis genes (TSC1 or TSC2) control cell growth; when the mutation occurs, the cells lose their ability to stop growing when conditions are such that normal cells would not grow, for example when nutrients are limited.
  3. Metastasis: LAM cells have been shown to move to other sites in the body and to recur in the donor lung of LAM patients who have undergone lung transplantation. Sporadic LAM involves mainly two organ systems, the kidney and the lung, and appears to spread via the lymphatics, which frequently become enlarged in the abdomen and chest. Lymph fluid build up (effusions) occur in many patients with LAM.
  4. Tissue destruction: LAM cells infiltrate and cause cysts in the lung leading to decreased respiratory function. LAM is very slowly progressive, resulting in the slow loss of lung function.
Determining the secrets of cancer is complex due to the multiple genetic mutations involved. In LAM there is only one primary gene mutation, thereby simplifying the study of how cells grow, metastasize and resist cell death. These are crucial areas of research in the study of cancer. This new way of thinking about LAM as a mild form of cancer, has lead prominent cancer researchers to participate in LAM research.

LAM Research – “Be Part of a Cure!”

Dr. William Stanford

“I think we’re on the cusp of real breakthroughs in using stem cells to further our understanding of disease and develop new treatments,” Dr. Stanford World-renowned scientist Dr. William Stanford will be partnering with a team of scientists at the McEwen Centre for Regenerative Medicine on the next stage of LAM research. Dr. Stanford’s work involves using genetic reprogramming techniques to turn adult human blood and skin cells into powerful embryonic-like stem cells. These “induced pluripotent” stem (iPS) cells can be grown in the laboratory and coaxed into giving rise to all of the specialized types of cells in the body. In the future, it may be possible to use iPS cell technology to provide an unlimited supply of personalized cells and tissues to replace those that have been damaged by disease, injury or aging. “His research truly is on the cutting-edge of stem cell science,” said a leading stem cell researcher.

The Stanford Lab Research Milestones

The first to reprogram transformed LAM patient-derived angiomyolipoma (AML) cells into induced pluripotent stem–like cells.

The first to reprogram cells from LAM lung explants to generate bona fide lung-derived induced pluripotent stem cell (iPSC) lines.

The first to reprogram cells from tuberous sclerosis complex patients and their tumours to make bona fide TSC2 mutant iPSC lines.

About the McEwen Centre

The mission of the McEwen Centre for Regenerative Medicine is to be a catalyst for regenerative medicine by facilitating collaboration, supporting research, and promoting awareness of the field. The Centre focuses on five branches of Discovery:
Heart, Neurology, Blood, Diabetes and Lung. Research is powered by a team of recent doctoral graduates recruited from around the world. Post-doctoral fellowships are a critical tool for supporting the work of the McEwen Centre. Their investigations allow the McEwen Centre to help find medical breakthroughs faster.

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