Andrew Lieberman, the Gerald Abrams Collegiate Professor of Pathology at University of Michigan Medical School in Ann Arbor, was awarded an MDA research grant totaling $300,000 over three years to test a modified antisense oligonucleotide (ASO) therapy to treat spinal-bulbar muscular atrophy (SBMA).

The work is part of an academic-industry partnership between Ionis Pharmaceuticals and the Lieberman laboratory. If successful, the work could de-risk further investment by Ionis.

Please describe your current research.

SBMA is a degenerative disorder of motor nerve cells and skeletal muscle caused by a mutation in the androgen receptor, the protein that binds male sex hormones. The disease causes progressive muscle weakness only in men, and no therapies are currently available.

My lab will be working to complete preclinical studies in a mouse model to establish the safety and efficacy of a new type of therapy to silence expression of the mutant gene. We will deliver this drug under the skin and target skeletal muscle; in fact, this new drug has been specially designed for efficient uptake by muscle.

Our central hypothesis is that the enhanced targeting of muscle by this new drug will enable robust gene silencing at lower doses, thereby limiting off target toxicity while concurrently enhancing activity in a variety of disease-relevant muscles.

These studies build upon our prior data pointing to significant benefits from this type of approach, and leverage the recent discovery of a chemical modification that increases drug uptake by skeletal muscle.

We will use genetic, biochemical, histological and behavioral analyses to accomplish these goals. We will (1) establish the extent to which this modified drug triggers enhanced gene silencing and prevents disease onset in SBMA mice, and (2) determine effects of this drug in symptomatic SBMA mice. These studies are expected to provide essential efficacy data in a preclinical model.

What is the focus of your research in SBMA, and why is it important?

We are interested in identifying mechanisms underlying disease pathogenesis in hopes of defining novel therapeutic agents and approaches.

We hope our work will translate into therapies for this currently untreatable disease.

What inspired you to study SBMA?

I began working on SBMA as a postdoctoral fellow with Dr. Kenneth Fischbeck. Dr. Fischbeck’s laboratory discovered the disease-causing mutation.

What is the expected outcome of your research?

Our studies are expected to provide essential efficacy data in a preclinical mouse model of SBMA.

How will your research lead to treatments and cures?

If successful, these data will help support efforts to translate this approach to patients.

Why is it important that MDA continue to fund research in SBMA?

There are no available disease-modifying treatments for SBMA. Grants from MDA provide critical support for translational studies in this area of unmet clinical need.

To learn more about how MDA research is accelerating treatments and cures for spinal-bulbar muscular atrophy, visit mda.org.