GSD1b Research Plan

Summary

Sophie’s Hope Foundation is the leading provider of funding and guidance for GSD1b research. We are the founding member and funding source of the GSD1b Patient Advocacy Organization, CureGSD1b (www.curegsd1b.org). This allows us to collaborate with other GSD1b groups to make sure we are as efficient and collaborative as possible. We also have developed relationships and partnerships with regional GSD organizations. Our global and world class Scientific and Medical Advisory Board includes 8 members (and growing) from 5 different countries, and is a diverse mix of clinicians, researchers, and industry experts. We also act as collaborators and guides with pharmaceutical companies working on developing treatments and a cure for GSD1b. We are actively investing in many diverse areas of research and will continue to do so. Below are some of our focus areas.

Natural History Studies and Data Collection – As we push towards new innovative therapies and a cure, it’s imperative that we deepen our understanding of GSD1b and its progression over time. This level of data will help us guide drug development properly and improve our chances of a successful therapy and cure. Natural History data will also be critical for any drug approvals from the US FDA and other government regulators in other parts of the world. Our first investment in this area is a multi-year grant to Duke University under the leadership of Dr Priya Kishnani. The more data we have about GSD1b the better our chances of a successful treatment and the better our chances of regulatory approvals.

Neutropenia – Until recently the only treatment option available for neutropenia in GSD1b was daily injections of G-CSF. G-CSF has many long-term negative side effects, is not particularly effective for all patients, and is also painful and expensive. In recent years a major discovery by Maria Veiga-Da-Cunha (SHF and CureGSD1b Scientific Advisor) and her team in Belgium has led to new treatment options for GSD1b. The discovery was that an SGLT2 inhibitor (used for Type 2 diabetes) could be used as a treatment option for neutropenia in GSD1b. The SGLT2 inhibitor helps remove a toxin (1,5AG) from the blood, which contributes to premature death of neutrophils in patients with GSD1b, which results in neutropenia. This treatment has proved very helpful for many patients, including Sophie, but there is still work to be done. Our focus now is to support further collaboration and understanding of this treatment, as we work with experts to develop better guidelines for use. We will also be supporting further research to understand the cause of neutropenia more completely, which could lead to an even more effective treatment.

mRNA Replacement Therapy – mRNA has become well known and popular thanks to Covid-19 and the vaccines developed by Moderna and Pfizer. The promise of mRNA extends beyond vaccines and into the rare genetic disease space. mRNA provides a great opportunity for disease modifying therapy for GSD1b. A treatment leveraging mRNA delivery is in early development for GSD1b and is an area of high focus for us. Initial pre-clinical studies in mice have shown great promise for GSD1b. The upside of mRNA is the safety of treatment and the lower expected cost of development and treatment. Also, due to the safety of mRNA, the expectation is that any clinical trials will be more efficient than traditional AAV based gene therapies.

Learn more about how mRNA can be used to treat rare diseases here: https://ultrarareadvocacy.com/understanding-drug-development/understanding-mrna-therapy/

Gene Editing – Gene editing aims to be a one-time therapy that directly edits pieces of DNA within the cell. It’s considered a type of gene therapy, which is the use of genetic material to treat or prevent disease. Gene editing has great potential to CURE rare genetic disease like GSD1b. We have early results that suggest GSD1b is a great candidate for next generation gene editing platforms, and we are currently in early stage development.

Learn more about Gene Editing here: https://patienteducation.asgct.org/gene-therapy-101/gene-editing

Basic Science – We are always looking to learn more about the pathophysiology of GSD1b. Basic science is what led to the discovery of SGLT2 inhibitors to better treat neutropenia in GSD1b.