CRISPR and Metachromatic Leukodystrophy (MLD)

A CRISPR-based approach to treat metachromatic leukodystrophy

Metachromatic leukodystrophy (MLD) is a rare autosomal recessive disease that arises from mutations in the ARSA gene, which encodes the Arylsulfatase A enzyme. Arylsulfatase A plays a key role in sulfatide (a type of fat) metabolism in brain cells, and its deficiency results in the accumulation of sulfatides in the brain. This leads to destruction of the protective myelin sheath, which surrounds the nerves in both the central nervous system and the peripheral nervous system. The resulting neurodegeneration leads to clinical manifestations that include halted or reduced motor and cognitive function. The disease may occur in different forms in infants, young persons and adults. All forms are progressive and result in premature death.

Current treatment options are by and large limited to symptom management and supportive care. Recently, researchers at the University of Tübingen, Germany, described a mutation-agnostic haematopoietic stem and progenitor cell (HSPC) gene therapy using CRISPR-Cas9 and an AAV repair template as a new potential treatment option for MLD. Their efforts led to efficient insertions and deletions and a high level of gene integration at the ARSA locus in human bone marrow–derived HSPCs, with no detectable off-target editing. They also demonstrated gene correction in HSPCs derived from two MLD patients with distinct mutations and demonstrated restoration of ARSA enzyme activity at levels similar to to healthy adults.

In this webinar, you will learn about:

• Introduction about MLD and similar diseases
• Cross correction as a therapeutic strategy for MLD
• Ongoing pre-clinical work to develop a CRISPR-based gene therapy for MLD

Tentative Webinar Programme:

• 15.00: Welcome and introduction by CRISPR Medicine News
• 15.05: Justin S Antony PhD, Junior Group Leader at University Children’s Hospital, University of Tübingen, Germany - Presentation: Haematopoietic Stem Cell Gene Therapy for treating rare monogenic diseases related to the brain
• 15.35: Q & A with Justin S Antony
• 16.10: Close by CRISPR Medicine News

Speaker/Title:

Justin S Antony PhD, Junior Group Leader at University Children’s Hospital, University of Tübingen, Germany - "Haematopoietic Stem Cell Gene Therapy for treating rare monogenic diseases related to the brain".

Justin S Antony, Junior Group Leader at University Children’s Hospital, University of Tübingen, Germany

Dr. Justin S Antony is a Junior Group Leader at the working group of Dr. Markus Mezger, University Children’s Hospital, University of Tübingen, Germany. Dr. Antony is a competitive advanced therapy scientist with a proven track record of success in both the biotech industry and academia. He is uniquely experienced in recent cutting-edge technologies including mRNA therapeutics, gene editing and gene therapy. Together with Dr. Mezger, part of his research focuses on the development of novel gene therapy modalities to treat rare genetic diseases, haemoglobinopathies, and cancer. Dr. Antony received his Bachelor’s degree from St. Xavier’s College, Palayamkottai, India and Master's degree from Bharathidasan University, India. Dr. Antony earned his Ph.D. from the University of Tübingen in the field of immunogenetics followed by postdoctoral research with Professor Michael Kormann at the University of Tübingen focused on mRNA therapeutics and gene editing. Dr. Antony holds both granted and pending patents and is a member of the American Society of cell and gene therapy network. He has published more than 25 research articles in peer-reviewed journals and received a handful of grants for his research.

Read also here the CMN interview we did with Dr. Antony in January 2022.