Rare Disease Report

New Collaboration Focuses on Gene Therapy for ALS

JANUARY 08, 2018
Mathew Shanley
Last week, Pfizer announced a new partnership with Sangamo. As part of the agreement, the two sides will team to develop a potential gene therapy to treat amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

Additionally, by using zinc finger protein transcription factors (ZFP-TFs), the candidates developed as part of the collaboration could also serve as a treatment for frontotemporal lobar degeneration (FTLD), another neurodegenerative disorder, linked to mutations of the C9ORF72 gene. Both conditions lead to the ultimate deterioration of motor neurons.

"We are excited to continue our collaborative relationship with Pfizer with this new program using Sangamo's zinc finger protein technology to develop a potential gene therapy for patients with certain forms of ALS and FTLD, devastating diseases with very limited treatment options," said Dr Sandy Macrae, Chief Executive Officer of Sangamo in a press release. "The precision and flexibility of zinc finger proteins enables targeting of virtually any genetic mutation. Collaboration with the right partner for a given therapeutic application is a key component of our corporate strategy and enables us to pursue the vast opportunity set of our platform."

Patients with ALS, a degenerative neuromuscular disease, have trouble walking, talking, and swallowing. When the muscles that control breathing fail, the condition quickly becomes fatal. There currently aren’t any approved treatments to halt muscle degeneration, and the ZFP-TF technology being used by the Pfizer and Sangamo is being designed to identify and bind to a precise sequence of DNA.

Once bound to the target DNA sequence, a transcriptional repressor domain attached to the ZFP suppresses the expression of that gene. This is unique as previous gene therapies and zinc finger nuclease-mediated genome editing that have been developed to replace or correct a missing or mutated gene or DNA sequence. The new ZFP-TF technology is designed to suppress the expression of specifically targeted genes, which permits for the targeting of an extensive range of diseases that require regulation of endogenous gene expression.

"We look forward to working with Sangamo on potential treatments for devastating diseases related to genetic mutations of the C9ORF72 gene," said Greg LaRosa, Senior Vice President and Chief Scientific Officer, Pfizer Rare Disease. "Pfizer is proud of the progress we have made in the area of gene therapy, which offers tremendous promise to patients and their families."

With the collaboration, Pfizer and Sangamo intend to investigate allele-specific ZFP-TFs with the intention of differentiating the mutant C9ORF72 from the wild type allele. Additionally, the team hopes to specifically down-regulate the expression of the mutant variation of the gene.

Under the agreement, Pfizer will pay Sangamo $12-million up front for the development of ZFP-TF candidates. Pfizer will take operational and financial responsibility for subsequent research, development, manufacturing, and commercialization for the C9ORF72 ZFP-TF program and any candidates or products that come as the result of the program. Additionally, Sangamo is eligible to receive potential development and commercial milestone payments of up to $150-million, as well as tiered royalties on net sales.

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