Our Every Drop Adds Up campaign builds on the idea that people coming together for a common goal can make the impossible happen, just as it did four summers ago when the ALS Ice Bucket Challenge soaked the world. Every person helped, research project funded, story shared, discovery made, piece of legislation passed, and auction bid placed – it all adds up!

By the beginning of 2019, three trials are slated to be underway to help develop antisense therapy for people with ALS, dividends on a bold investment The ALS Association made in 2004, when the technology was new. We sat down with Dr. Don Cleveland, a pioneer in the field, for the second part of our series highlighting antisense technology.

Dr. Cleveland, professor at the University of California, San Diego’s Ludwig Institute for Cancer Research, is a long-time funded ALS researcher. He has been working with The ALS Association since 2004 to develop DNA-based designer drugs to silence ALS genes, called antisense gene silencing or antisense technology.

In 1999, The ALS Association, along with the American Academy of Neurology, awarded Dr. Cleveland with the prestigious Sheila Essey Award for his significant contributions to research. He was recently awarded the $3 million prestigious 2018 Breakthrough Prize in Life Sciences for his numerous accomplishments in neurodegenerative disease research, including establishing antisense therapy in animal models of ALS.

He talked with us to discuss this important gene silencing technology that currently targets inherited ALS genes and could be potentially applied to non-inherited (sporadic) ALS in the future.

“With The ALS Association’s ongoing support, my work in [the] development of designer DNA drugs, which is frequently called antisense technology, for therapy of neurodegenerative diseases – once widely considered by almost everyone to be doomed to failure – has led to clinical trials that could help people with ALS and other neurodegenerative diseases.” (Dr. Don Cleveland)

Q: Thank you for joining us today. How has The ALS Association contributed to your work in antisense technology?

A: Support for designer DNA drug technology began in 2004, exclusively with The ALS Association support, against deep skepticism that the approach would be useful. In the 14 years since it was initiated, it has now fueled clinical trials in up to four diseases, including up to two trials in ALS. There has been a transformation of thinking that these gene silencing approaches are probably applicable broadly in human neurologic disease and most especially for ALS.

The ALS Association should take full credit because it was they who invested right from the beginning and continued to invest over that decade. That investment has generated two gene silencing trials for the two most frequent causes of inherited ALS – C9orf72 and SOD1 (as well as additional trials in spinal muscular atrophy, Huntington’s and Alzheimer’s diseases).

And going forward, the designer DNA drug approach is highly appropriate for maintaining synthesis of a protein lost in sporadic ALS that we have just shown to be essential for neuronal regeneration, meaning the repair of neurons damaged by ALS.

The ALS Association’s support has been transformative for my work. With Ice Bucket Challenge donations, The ALS Association was able to double down on its investment in designer DNA drugs that target C9orf72, the most common genetic cause of ALS, which will likely enter clinical trials in the fall of 2018.

Q: What other projects is The ALS Association supporting that have led to significant impacts on the ALS field?

A: By the end of 2018, The ALS Association support will have fueled three new gene silencing trials in ALS that include SOD1 antisense, C9 antisense, and adeno-associated virus (AAV) delivery of antisense. This includes:

1. Development of a designer DNA drug (antisense technology) therapy for the most frequent cause of inherited and sporadic ALS – mutation in the C9orf72 gene. Clinical trial initiation is anticipated in fall 2018
2. Development of gene silencing therapy within the nervous system delivered by AAV, a versatile type of virus that is engineered for delivery of gene therapies. This approach enables a one-time therapy to suppress ALS-causing mutations in superoxide dismutase (SOD1). Clinical trial initiation is anticipated in first quarter 2019.
3. Development of an improved method of AAV delivery to silence any target gene throughout the spinal cord and motor neurons in the brain. With this approach, we have the potential to eliminate motor neuron disease progression by applying our therapy right after disease onset.

We are pleased that the Association is continuing with a vision that can see beyond short-term approaches and is continuing to enable the kinds of approaches that could be truly field redirecting. Their dedicated support of antisense technology is a great example of their forward thinking.

We proudly continue to support Dr. Cleveland’s cutting-edge research through the Neuro Collaborative, a unique academic-industry program in California that is focused on curing ALS and was launched by our Golden West Chapter. We can’t wait to see what he does next!

For more information about antisense technology and its impact on the ALS field, click here and here.

For more detailed information about Dr. Cleveland’s recently funded projects, click here and here.