Gregory and Deborah Macres lost their son Gregory in 1997 to Gaucher disease, a rare genetic disorder. Four-year-old Gregory died after an unsuccessful experimental treatment. Despite their personal loss, the Macreses did not abandon the drive to find a cure, setting up a charitable foundation to support research in several laboratories around the world, including that of Prof. Anthony Futerman in the Biomolecular Sciences Department at the Weizmann Institute of Science.
Now, after 25 years of research, Weizmann scientists have discovered an innovative genetic treatment that has shown promising results, with possible applications to other diseases like Parkinson's.
Gaucher disease is caused by an inherited defect in an enzyme the body uses to break down a fatty substance called glucocerebroside. When this substance is not broken down, it accumulates – causing brain damage that can be fatal. The disease is relatively more common among Ashkenazi Jews, who usually have the least severe type, which does not lead to brain damage. The two other variants of the disease are much graver: Gaucher Type II causes severe brain damage, with a rapid worsening of symptoms and death before age 2, while for people with Type III, the fatal brain damage occurs later in childhood or even in adulthood.
Current treatment, injections of undamaged enzymes, does not cure the disease, nor does it prevent severe brain damage. This is because the dense layer of cells that surround blood vessels in the brain prevents the enzymes from reaching their target. Consequently, the more severely affected patients still do not have a viable treatment.
Using an advanced algorithm they had created, scientists in Prof. Sarel Fleishman’s lab designed a version of the gene that would not only carry the right recipe for the enzyme, but would carry an improved recipe leading to a particularly active and stable version capable of compensating for the genetic defect and combating the accumulation of glucocerebroside, reducing brain inflammation, a key role in the disease’s progression.
In their new study, they found that the expression level of both this marker and two additional inflammatory genes drops in samples that receive the new treatment.
“For a quarter of a century, the Macres family has been following my research and I have been updating them on every development. The innovative gene therapy for the version of Gaucher disease that took their son Gregory feels like a kind of closure for me,” an emotional Futerman said. “We hope to find partners to help us take this innovative treatment forward – from a more extensive experiment to clinical trials in people. There is a lot of interest in this research beyond Gaucher disease, which is relatively rare, because studies show that the defective gene also increases the risk of Parkinson’s disease.”