The ANA Q&A: New Frontiers in ALS

In the month of May, we are also drawn to awareness of Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease or motor neurone disease, as it causes the death of neurons controlling voluntary muscles. The ANA tapped Laura P.W. Ranum, Ph.D, former chair of the Scientific Program Committee for the ANA Annual meeting, to bring us up to date on recent developments in her lab and beyond.

Dr. Ranum is the Founding Director of the Center for NeuroGenetics and Professor of Molecular Genetics and Microbiology at the University of Florida in Gainesville. Over the past 25 years her laboratory has identified the mutations for a number of neurological disorders including spinocerebellar ataxia types 5 and 8 (SCA5, SCA8), and myotonic dystrophy type 2 (DM2). Her laboratory has developed and uses mouse models to understand how these and other mutations cause disease.  Most recently, the Ranum lab created a mouse model of the C9orf72 ALS/dementia mutation that has generated wide interest in the scientific community studying Amyotrophic Lateral Sclerosis (ALS).

Q. What does the public need to understand about ALS that it often doesn’t?

Patients and families with ALS need to understand that genetic testing to define the type of ALS they have is important. Knowing this may put patients in a better position to participate in clinical trials and to receive future therapies. New therapies are being developed for specific genetic forms of ALS and so identifying if there is a specific gene that causes a patient’s ALS may enable that person to receive future therapies that target that specific type of ALS at the gene level.

"Patients and families with ALS need to understand that genetic testing to define the type of ALS they have is important.”


Q. How are treatment options for ALS different today than 10 years ago?

We now understand more about the genes that cause ALS and the cellular pathways that are affected in the disease. This has enabled the research community to develop more targeted treatment options. Some of these potential treatments are gene-targeted therapies specific for different genetic causes of ALS. Others are general, neuroprotective strategies which target cellular pathways affected in the disease that may be beneficial for multiple different genetic and non-genetic forms of ALS.

Q. What promising research is poised to change the standard of treatment for ALS?

The development of antisense oligonucleotide (ASOs) therapies is changing the standard of treatment for motor neuron diseases. An ASO based therapy is now FDA approved for treatment of spinal muscular atrophy (SMA), another form of motor neuron disease, where its use has had great impact on the SMA community. This has paved the way for ASO treatment of other neurodegenerative diseases and ASOs are now in clinical trials for different genetic types of ALS. With the progression of these clinical trials, ASOs have the potential to change the standard of treatment for ALS and other neurodegenerative diseases.

Q. What work is your lab undertaking to move ALS understanding or treatment forward?

My lab is currently focusing on understanding and developing treatment strategies to target pathways that affect the accumulation of unexpected proteins, called repeat-associated non-ATG (RAN) proteins in a form of ALS caused by a repeat expansion mutation in the C9orf72 gene, a common cause of both familial and sporadic ALS.These experimental strategies, which are being tested in mouse models of the disease, are designed to target the production and turnover of the RAN proteins in order to reduce their levels and improve the disease phenotypes.

Q. How has the ANA supported your career or work in this area?

Interacting with both clinical and basic scientific colleagues at the ANA Annual Meeting and as a member and former Chair of the Scientific Program Committee has been a privilege. The ANA provides opportunities to foster interdisciplinary discussions and collaborations that have improved both basic scientific research and clinical care and help to keep all of our research on track and moving towards the goal of curing ALS and other neurologic conditions.