issue Spring 2022

Developing Precision Medicines for Rare Diseases

By Judy Masterson
Dr. Hastings, at left, works with Wren Michaels, PhD.

Michelle Hastings, PhD, looks forward to the day that she can give hope to parents of children with genetic diseases who reach out to inquire about potential treatments.

“I get emails all the time from families of newly diagnosed patients who are racing to find a drug or therapeutic,” said Dr. Hastings, who serves as director of the Center for Genetic Diseases. “I would love to say, ‘Yes! We do have an ASO that we’ve already tested.’ But we’re only partway down that path.”

ASOs, or antisense oligonucleotides, are tiny pieces of RNA or DNA designed to modify gene expression by binding to specific RNA molecules to alter production of proteins required for cell health.

We’re quickly realizing that most diseases have a genetic component.

Dr. Hastings, in collaboration with experts in different diseases at RFU, has designed numerous potentially therapeutic ASOs — the first in 2009 for Usher syndrome, which causes childhood deafness and blindness. The university holds a portfolio of ASO patents based on her work on Usher syndrome, cystic fibrosis (CF), Parkinson’s and Batten disease, and Alzheimer’s disease. The latest was granted for a promising new therapeutic approach for the treatment of a difficult-to-treat mutation that causes CF, a devastating lung and multi-system disease. Described in a recent study published in the Proceedings of the National Academy of Sciences, the approach uses ASOs in combination with approved CF drugs for patients with a specific class I mutation in the disease-causing gene.

“We’re quickly realizing that most diseases have a genetic component,” Dr. Hastings said. “Many of them are very specific and personal to each individual. So these types of individualized, precision medicines that can be developed in a very specific, mutation-targeted way are gaining in interest and importance.”

From left: Dr. Hastings, senior research associate Cecilia Pena Rasgado and Dr. Michaels.

Patent protection allows RFU to move promising therapeutic approaches into development — to draw interest from companies that will support clinical trials, product development and commercialization. While only a few ASO therapeutics have been approved by the FDA, many disease-based applications are in the pipeline, and the agency is working to advance their development.

Dr. Hastings looks to a future in which a toolkit of ASO strategies will be available to treat mutations in every one of the human genome’s estimated 30,000 genes.

“Every day, we find more diseases and pathological conditions that are caused by genes of unknown function,” she said. “I’m really excited about the work we’ve done so far, which has demonstrated the initial efficacy of the platform and brought recognition and appreciation for it. I’ll feel really successful once we get drugs in humans.”