CLINIC FOR BPAN &

WDR45 -RELATED DISORDERS

CENTER FOR GENOMIC MEDICINE, DEPARTMENT OF NEUROLOGY AND CENTER FOR RARE NEUROLOGY DISEASE AT MASS GENERAL HOSPITAL MEDICAL SCHOOL

January 31, 2022

Co – Funded with

Our research is focused on therapy-oriented studies of ultra-rare pediatric neurologic diseases with high unmet medical need. We are supported by Don’t Forget Morgan to perform design and early preclinical development of AAV-mediated gene therapy for BPAN. Having a strong background in studies of autophagy and lysosomal biology in the context of brain health and neurodegeneration, we will also investigate whether either pharmacological or AAV-mediated approaches for autophagy/lysosomal enhancement can compensate autophagy deficits in BPAN, therefore providing novel therapeutic targets for this devastating disease.

RESEARCH

UNIVERSITY OF MICHIGAN

Two Year Grant Awarded to U of M

The University of Michigan's Department of Neurology is home to Sami Barmuda, M.D., Ph.D., and Jason Chua, M.D., Ph.D., two researchers who perform cutting-edge research on the kind of autophagic processes found in BPAN and other NBIA disorders. Dr. Barmuda is the Angela Dobson and Lyndon Welch Research Professor of Neurology at U-M. The laboratory he established in 2013 applies the newest technologies to the study of neurodegenerative diseases. His lab has significant expertise in the study of autophagy, among other areas, and Dr. Chua had the good fortune to spend his residency working under the mentorship of Dr. Barmuda. Dr. Chua is a clinical lecturer in the Department of Neurology, as well as a research fellow and movement disorders clinical fellow. Together, they are investigating the mechanisms which regulate autophagy. Given the young lives they’re racing to save, their research has never been more important.

RESEARCH- SANFORD

Louis-Jan (LJ) Pilaz, PhD

Dr. LJ Pilaz studies the cellular and molecular mechanisms that regulate the development of the cerebral cortex and how their disruption can lead to neurodevelopmental diseases. He received his PhD in Lyon (France), and then moved to the US where he trained as a postdoctoral fellow at Johns Hopkins School of Medicine and Duke University. He is a father to four beautiful daughters.

BPAN SPECIFIC RESEARCH:
Sanford Research was awarded a grant to implement a new technology (called iGONAD) that was initially developed as a partnership between a lab in Japan and another one in Omaha, Nebraska.

When you are using traditional methods, making a mouse model harboring a mutation for a specific gene can be very expensive and takes a lot of time. This technology is a game changer and allows you to get around these two issues.

SANFORD RESEARCH GRANT

July 31, 2020

The goals of our current research grant is to generate novel genetically engineered mouse models (GEMMs) of BPAN. Since BPAN results from reduced expression of the WDR45 gene, the first GEMM will use a knockout approach to replicate the loss of function observed in BPAN patients. The second GEMM will produce a WDR45 protein fused to BioID and will thus enable the identification of the proteins operating in the vicinity of WDR45 in vivo. This will allow the identification of key molecular pathways involved in BPAN disease.

This approach will rely on the iGONAD technique, consisting in the combination of CRISPR technology, together with in utero electroporation one day following fertilization.

The COVID pandemic did not deter us from doing experiments related to this project. Of note, the success of the current experiments conducted in the lab have been inspiring, and will enable us to attack BPAN questions with another angle in future research.