When clinical trials began two years ago for treatment of Late Onset Tay-Sachs with the drug Zavesca, the trial was scheduled to last one year, with a possible 12-month extension. But because LOTS is such a rare disease, with only 200 known cases nationwide, researchers at New York University’s School of Medicine and the University Hospital of Cleveland decided to extend the trials for a third year before arriving at any conclusions.
Zavesca, also known as OGT918 or miglustat, works as a substrate inhibitor to reduce the buildup of GM2 ganglioside, waste material that LOTS patients cannot break down properly because of a deficiency in the Hex-A enzyme.
Initial toxicity findings show that the drug “appears to be fairly tolerated and safe,” said Dr. Barbara Shapiro, associate professor of neurology at University Hospital of Cleveland.
Thirty patients, 80% of them Jewish, are participating in the trials. LOTS, like infantile Tay-Sachs, is a Jewish genetic disease; with LOTS, however, symptoms begin to appear in adolescence and early adulthood. Because it is such a rare disease, patients are commonly misdiagnosed and often don’t know they have LOTS for years after they begin noticing symptoms, which include problems with speech, gait and muscle control. The severity of the disease, which also manifests itself in psychological illness, varies greatly among patients.
Even in the best possible scenario, Zavesca is not an end-all solution to LOTS, and other approaches to treatment are being pursued.
Dr. Don Mahuran, professor at the University of Toronto and senior scientist at the Hospital for Sick Children, is working on enzyme enhancer therapy, an approach that will use a compound called NGT, a synthetic carbohydrate that binds to and stabilizes the area in the enzyme responsible for digesting ganglioside. NGT is expected to enhance the ability of the mutated enzyme to assemble correctly during its biosynthesis, and thus function properly in the breakdown of Tay-Sachs ganglioside.
Mahuran sees his approach as an appropriate supplement to the Zavesca treatment. According to Mahuran, the side effects of the drug can be reduced by lowering the dosage and increasing enzyme levels. He believes that together, the treatments can work synergistically.
— SHOSHANA OLIDORT
Low-fat Diet and Cancer
A recent study conducted at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center has concluded that a low-fat diet may help women who have had breast cancer avoid a recurrence, according to an article posted at the American Cancer Society’s Web site.
The study took 2,500 postmenopausal women, aged 48 to 79, who had been treated for early-stage breast cancer with surgery and regular follow-up care, and randomly assigned 975 of them to a low-fat diet of 33 grams daily. Other participants were asked to follow their normal diets, generally consisting of a fat intake of 51 grams.
After five years of follow-up, the low-fat diet helped women with estrogen-negative tumors lower their risk of recurrence by 42%. However, the diet did not significantly affect recurrence in women with estrogen-positive tumors.
Since fat affects estrogen production and estrogen itself, in turn, fuels certain breast cancers, the study’s finding that only those with estrogen-negative tumors were affected by the low-fat diet hinted that other mechanisms are at play in causing breast cancer to recur.
Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society, said in the article that because about one-third of postmenopausal women develop estrogen-negative breast tumors, the new findings are exciting, although he cautioned that they are still preliminary.
The study’s lead researcher, Dr. Rowan Chlebowski, said the findings “may well represent the first lifestyle change — namely lowering dietary fat intake — that can have a favorable effect on breast cancer outcome.”
For now, in any event, Lichtenfeld said, “there’s never harm in following a balanced low-fat diet.”
— SARAH GIVNER
Gaucher Month Named
The National Gaucher Foundation has designated September as National Gaucher Disease Awareness Month, to promote awareness of a disease that is prevalent in the Ashkenazic Jewish community.
As part of its effort, the NGF will sponsor a series of presentations in major American cities, at which it will distribute a recently completed DVD, “A Message to Elijah,” narrated by well-known actor Elliott Gould, according to an NGF press release. The digital documentary outlines the causes and treatments of Gaucher disease, the most common of the Jewish genetic diseases, and gives viewers a glimpse into the lives of people suffering with the debilitating illness.
“For those most at risk, it is vital to know and recognize the warning signs of Gaucher disease and gain access to proper treatment,” said Rhonda Buyers, executive director of the NGF, in the release. “National Gaucher Disease Awareness Month has been established to educate at-risk individuals of the disorder and their physicians to ensure proper diagnosis and appropriate care,” Buyers said.
Gaucher disease affects one in every 450 to 600 children born in the Ashkenazic Jewish community. It is caused by an enzyme deficiency that results in excessive accumulation of waste materials in patients’ bone marrow and body tissues. The NGF is dedicated to finding a cure for Gaucher by funding research and increasing awareness in the Jewish population and among physicians.