Toward a less expensive, more convenient treatment of Gaucher's disease

May 24, 2006

Prospects for eventual development of a less costly and more convenient treatment for Gaucher's disease have brightened with new research findings reported in the May issue of ACS Chemical Biology.

The existing treatment costs up to $750,000 annually for a single patient, continues for life, and must be given intravenously rather than by mouth. An oral treatment based on the new research could cut those costs by 100-fold.

Gaucher's (go-SHAYZ) disease is rare, but ranks as the most common lysosomal storage disorder and genetic disorder affecting Jewish people of Eastern European ancestry. Individuals with Gaucher's disease, which can be fatal, produce a defective form of GC, a critical enzyme that breaks down a fatty substance called glucosylceramide.

In the new report, scientists have confirmed experiments they reported initially in 2002 that "chemical chaperones" can partially correct the genetic defect responsible for most cases of Gaucher's disease. Like aspirin, penicillin and most other existing drugs, chemical chaperones are small molecules -- natural and synthetic substances with a low molecular weight.

Using patient-derived cell lines, researchers have extended those earlier studies to provide new insights into the defect and how chaperones correct it. The defect involves protein misfolding and prevents a key enzyme, glucocerebrosidase (GC), from reaching the location in cells where it normally functions. Jeffrey W. Kelly, Ph.D., of the Scripps Research Institute (TSRI) in La Jolla, Calif., headed the research team.

"Gaucher's disease patients can now be treated with enzyme replacement therapy," Kelly explained. "The hope is that this current strategy could be replaced with a small molecule chemical chaperone therapy wherein the cost would be reduced by at least 100-fold." Although enzyme replacement therapy is highly effective in treating Gaucher's disease, treatment often costs $100,000-$750,000 annually for each patient. With abnormal glucosylceramide, Gaucher's patients accumulate GC in the spleen, liver, lungs and bone marrow. As those cells become engorged with the enzyme, patients experience a range of health problems including anemia, bone fractures and sometimes lung and brain disorders. Kelly said researchers are now trying to identify an optimal small molecule that could be suitable for use as a chemical chaperone in clinical trials.

The research team included Anu R. Sawkar, Ph.D., and William E. Balch, Ph.D., of TSRI; Martina Schmitz, Ph.D., and Klaus-Peter Zimmer, Ph.D., of Westfälische Wilhelms-Universität in Münster, Germany; and David Reczek, Ph.D., and Tim Edmunds, Ph.D., of Genzyme in Cambridge, Massachusetts.
The American Chemical Society -- the world's largest scientific society -- is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

-- Michael Woods

The online version of the research paper cited above was published May 23 on the journal's Web site. Journalists can arrange access to this site or request a copy of the paper by sending an e-mail to or calling the contact person for this release.

American Chemical Society

Related Bone Marrow Articles from Brightsurf:

Researchers identify the mechanism behind bone marrow failure in Fanconi anaemia
Researchers at the University of Helsinki and the Dana-Farber Cancer Institute have identified the mechanism behind bone marrow failure developing in children that suffer from Fanconi anaemia.

Nanoparticles can turn off genes in bone marrow cells
Using specialized nanoparticles, MIT engineers have developed a way to turn off specific genes in cells of the bone marrow, which play an important role in producing blood cells.

How stress affects bone marrow
Researchers from Tokyo Medical and Dental University (TMDU) identified the protein CD86 as a novel marker of infection- and inflammation-induced hematopoietic responses.

3D atlas of the bone marrow -- in single cell resolution
Stem cells located in the bone marrow generate and control the production of blood and immune cells.

Dangerous bone marrow, organ transplant complication explained
Scientists have discovered the molecular mechanism behind how the common cytomegalovirus can wreak havoc on bone marrow and organ transplant patients, according to a paper published in the journal Cell & Host Microbe.

Viagra shows promise for use in bone marrow transplants
Researchers at UC Santa Cruz have demonstrated a new, rapid method to obtain donor stem cells for bone marrow transplants using a combination of Viagra and a second drug called Plerixafor.

Bone marrow may be the missing piece of the fertility puzzle
A woman's bone marrow may determine her ability to start and sustain a pregnancy, report Yale researchers in PLOS Biology.

Cells that make bone marrow also travel to the womb to help pregnancy
Bone marrow-derived cells play a role in changes to the mouse uterus before and during pregnancy, enabling implantation of the embryo and reducing pregnancy loss, according to research published Sept.

Uncovering secrets of bone marrow cells and how they differentiate
Researchers mapped distinct bone marrow niche populations and their differentiation paths for the bone marrow factory that starts from mesenchymal stromal cells and ends with three types of cells -- fat cells, bone-making cells and cartilage-making cells.

Zebrafish help researchers explore alternatives to bone marrow donation
UC San Diego researchers discover new role for epidermal growth factor receptor in blood stem cell development, a crucial key to being able to generate them in the laboratory, and circumvent the need for bone marrow donation.

Read More: Bone Marrow News and Bone Marrow Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to