Scribe, Biogen Partner to Combat ALS using Nobel Prize-Winning CRISPR Technology

By Daniel Ojeda, Ph.D.

Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s disease is a progressive nervous system disease that causes muscle control loss, including muscles necessary for breathing. Most patients are diagnosed with sporadic ALS, and around 10% of the patients have familial ALS. There is no cure for this disease, and most patients die of respiratory failure within 2-5 years of onset. Currently, Riluzole and Edaravone are the two FDA-approved drugs used for disease management. Riluzole has shown to extend survival time between 6 to 21 months in some studies.

On October 6th, 2020, Scribe Therapeutics Inc. and Biogen Inc. announced a partnership to develop CRISPR-based therapeutics to fix ALS’s underlying genetic cause. CRISPR, often referred to as “genetic scissors,” is a radical breakthrough of this century for which Dr. Emmanuelle Charpentier (Max Planck Unit for the Science of Pathogens, Berlin, Germany) and Dr. Jennifer A. Doudna (University of California, Berkeley, USA) have been conferred the 2020 Nobel Prize in Chemistry.

Scribe, Biogen Deal

Dr. Doudna is the co-founder and scientific advisor of Scribe, a company specializing in engineering synthetic CRISPR molecules that can bind to specific DNA fragments, allowing scientists to modify or eliminate disease-causing genes. This ability for genetic engineering and manipulation holds enormous potential for therapeutic applications. In the case of ALS, there are two genes linked to its development, C9ORF72 and SOD1. These genes account for 37 to 60 percent of all familial cases of ALS and could theoretically be targeted by CRISPR to cure the disease.

Using this premise, Scribe and Biogen will develop and commercialize therapeutics for genetically driven ALS and pursue other targets involve in neurogenerative disease. Scribe has previously developed X-Editing (XE), their first technology, which is said to offer greater activity, specificity, and deliverability for their CRISPR molecules. These are key to modify disease-causing genes successfully. This deal is in line with Scribe’s goal to address a wide range of diseases with significant unmet medical needs.

Scribe Therapeutics will receive $15 million upfront and up to $400 million in potential development and commercial milestone payments under the agreement. Additionally, Scribe could receive from high single-digit to sub-teen royalties from Biogen.

“We’re proud to collaborate with Biogen and apply our uniquely customized approaches with the goal of developing new, safe, and effective genetic medicines for neurodegenerative disease,” said Benjamin Oakes, CEO and Co-Founder of Scribe Therapeutics.

The Unknowns of CRISPR

Even with the incredible potential, it is important to remember the limitations of CRISPR technology such as off-target effects. The first clinical trial using CRISPR directly in patients was approved in 2019 to treat Leber Congenital Amaurosis, which lead to inherited childhood blindness. The clinical trial, which is set to conclude in 2024, would provide great information regarding any side effects.

Additionally, a recent study published in Nature Genetics showed that CRISPR interference could lead to the emergence or expansion of cells with a mutant version of the p53 protein, a protein involved in DNA repair and cancer prevention. This is the first peer review paper on the subject, but it comes on the heels of another preprint article showing CRISPR can select for cancer-driving mutations. Although further research is necessary, this observation opens the possibility of potential side effects warranting the use of CRISPR-based therapeutics with guarded optimism.

Editor: Rajaneesh K. Gopinath, Ph.D.

Related Article: CRISPR Pioneers Bag 2020 Nobel Prize in Chemistry

References

1. https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/symptoms-causes/syc-20354022#:~:text=Amyotrophic%20lateral%20sclerosis%20(a%2Dmy,who%20was%20diagnosed%20with%20it.
2. https://www.ajmc.com/view/overview-of-current-and-emerging-therapies-for-amyotrophic-lateral-sclerosis
3. https://www.businesswire.com/news/home/20201006005510/en/Scribe-Therapeutics-Unveils-Fully-Integrated-Platform-for-Engineering-Breakthrough-CRISPR-based-Genetic-Medicines
4. https://www.nature.com/articles/s41588-020-0623-4
5. https://www.biorxiv.org/content/10.1101/407767v2

Author

Daniel Ojeda