Meet Dr. Don Cleveland: Prominent ALS Researcher Who Pioneered Antisense Technology

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.

don cleveland photo 230
Dr. Don Cleveland


“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.

There has never been a more optimistic time for the development of therapies, like antisense therapy, for many people with ALS. Donate now and stand with us to make your greatest impact in the fight for a world without ALS.

You can also support the fight against ALS by sharing stories from our ALS community, bidding on an ALS Auction item, telling us your story, picking up a PopSocket, or hosting a fundraiser.

As the ALS Ice Bucket Challenge proved, small actions can have a major impact. Or, as we like to put it, Every Drop Adds Up! Thanks for your support!

6 thoughts on “Meet Dr. Don Cleveland: Prominent ALS Researcher Who Pioneered Antisense Technology”

  1. my husband had als, he died in 1999 at age 63, he was treated here in cleveland at the cleveland clinic,his sister died from altice acid defficentcyooboy I hope I spelled right. I have always felt there has to be a connection between these 2 . to have a brother and a sister with these 2 rare diseases must have a connection.. just a thought. thank you

    caroline paull


  2. Her daughter was diagnosed about a year-and-a-half ago. At this point it only affects her left arm she is right handed fortunately. She’s very intelligent she’s very small she has two young children 5 and 7 she will try any trial medicines what she appears to be taking and I don’t know what that is. She lives in Seattle one of her doctors I believe is out of the University of Washington. She will get on any trial medicines she will do whatever it takes and and the disease does not appear to have progressed much in the last year-and-a-half other than the left arm. I can send her or give her any information that you suggest cuz she’s a perfect candidate and good help other than this horrible disease. We are very proud of her cuz she’s face this head-on, she is on a special diet of Our Own and works on it religiously. Her name is Kristi Forsythe she is 38 and we want her to be a mom a wife and daughter for many many years.


  3. Hi Jack Kelley hope you are doing great, I am so scared. I have bodywide twitching and weird sensations going on in my left hand, I have had 4 emgs which came back normal but symptoms direct to Als is it possible if i can somehow speak to Kristi Forsythe ?


  4. Thank you for your work!!! My mother was diagnosed in 2015 and sadly died in 2016. I am very curious to know if I have the gene. I am wondering how I can find this out… any help would be very appreciated.
    Thank you


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