Breakthrough discovery at NYU Langone Medical Center offers new hope for Gaucher’s Disease treatment

Researchers at NYU Langone Medical Center in New York City have made an unexpected breakthrough in the treatment of Gaucher’s Disease, an inherited enzyme disorder, while conducting a regular study on asthma. This discovery has the potential to revolutionize the approach to treating this rare genetic condition, which predominantly affects individuals of Eastern and Central European Jewish descent.

Unintended Discovery Leads to Potential Therapeutic Advancement

Gaucher’s Disease is characterized by the accumulation of fatty substances in cells and organs due to a mutation in genes that encode lysosomal enzymes necessary for digesting glycolipids. Symptoms of the disease include joint pain, blood disorders, enlarged spleen and liver, memory loss, and lung damage. Traditional treatments have focused on replenishing lysosomal GBA (beta-glucocerebrosidase), an approach that provides temporary relief but requires continual application as the enzyme levels are steadily depleted.

The NYU team’s research into asthma led to a serendipitous discovery regarding the role of progranulin, a protein crucial in the pathology of Gaucher’s Disease. Progranulin typically aids in the delivery of enzymes to lysosomes, the cellular structures where waste is broken down. In Gaucher’s patients, the process is flawed due to abnormally high levels of GBA production outside the lysosomes.

The Role of Synthetic Progranulin in Treating Gaucher’s Disease

The study’s findings, led by Chuanju Liu, PhD, a senior investigator and professor in the Departments of Orthopaedic Surgery and Cell Biology at NYU Langone, indicate that synthetic progranulin, named Pcgin, could significantly reduce GBA clumping. In tests conducted on blood cells from Gaucher’s Disease patients, Pcgin led to a 40% reduction in GBA accumulation within just one week.

“Our results suggest a new way to treat Gaucher’s disease that corrects abnormal enzyme delivery by progranulin to lysosomes,” said Dr. Liu. This new method contrasts sharply with existing treatments, focusing on a more sustainable and potentially curative approach.

Furthermore, Pcgin has shown to be more stable than natural progranulin, eliminating risks associated with tumor-like cell growth in test animals. This enhancement increases its viability as a therapeutic option, offering hope for a more effective treatment regimen.

Implications for Broader Medical Treatments

Jian Jinlong, MD, PhD, a lead investigator at NYU Langone, emphasized the broader implications of their findings. “Our new experiments are the first to explain why reduced progranulin is a key characteristic of Gaucher’s, and why the mice engineered to lack the protein serve as such a good model to test new therapies,” he stated.

The discovery also has implications for treating related conditions, as the research indicated that Pcgin could reduce lung tissue swelling in progranulin-deficient mice by over 60%, mirroring the effects of current GBA-replacement treatments.

Funding and Future Research

The research is supported by grants from the National Institute of Health and a grant from Atreaon, a pharmaceutical company specializing in arthritis treatments. NYU Langone has entered into a drug-licensing agreement with Atreaon, underlining the potential for these findings to be developed into a viable drug.

This breakthrough represents a significant advance in the understanding and treatment of Gaucher’s Disease. By targeting the fundamental issues of enzyme delivery, this approach could lead to more sustainable and effective therapies for patients suffering from this debilitating condition.