The Macres family, despite personal loss, has tirelessly pursued a cure for Gaucher disease, establishing a foundation to fund research globally, including at the Weizmann Institute of Science under Professor Anthony Futerman. After 25 years of research, a new study in Gene Therapy reveals a groundbreaking genetic treatment that has shown promising results in mice, leading to significant increases in lifespan and motor function preservation.
Gaucher disease results from a hereditary defect in an enzyme responsible for breaking down glucocerebroside, a fatty substance. This accumulation damages cellular recycling centers called lysosomes, posing fatal risks. The disease is particularly prevalent among Ashkenazi Jews, with Type I being the least severe. Types II and III are more severe, leading to neurological damage and early mortality.
Current treatments involve repeated enzyme injections to reduce glucocerebroside accumulation but do not cure the disease or address severe types due to the blood-brain barrier. Recent research has focused on gene therapy, where a normal copy of the defective gene is inserted into cells using a virus. However, simply inserting a normal gene does not necessarily rectify the genetic defect.
In a collaborative effort, Futerman's lab worked with Professor Sarel Fleishman's team to create an enhanced gene version that produces a more active and stable enzyme. This modified gene was injected into young mice with a condition mimicking Gaucher Type III. Results indicated that treated mice gained weight and lived significantly longer, maintaining motor function, unlike untreated mice.
Further analysis showed that the modified gene significantly reduced glucocerebroside accumulation and inflammation in the brain. The team discovered a correlation between elevated inflammatory markers and disease severity, suggesting inflammation plays a crucial role in brain damage.
Futerman expressed hope that this innovative gene therapy could lead to clinical trials, highlighting its potential beyond Gaucher disease, particularly regarding its association with Parkinson's disease. The study included contributions from various researchers at the Weizmann Institute.