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Sangamo, Pfizer Partner on ALS Gene Therapy

Brain synapses illustration

(AllanAjifo, Wikimedia Commons)

3 January 2018. Drug maker Pfizer Inc. is licensing and collaborating on a gene therapy technology from Sangamo Therapeutics Inc. to treat amyotrophic lateral sclerosis, or ALS, and a related neurodegenerative disease.  The deal with Pfizer could bring the Richmond, California-based Sangamo Therapeutics as much as $162 million if all phases of the agreement are fulfilled.

ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder where neurons or nerve cells controlling muscles in the body begin to waste away, and can no longer send or receive signals from the brain or spinal cord. As the nerve cells stop functioning, the muscles in the limbs, and later speech and breathing muscles, begin weakening and eventually stop functioning. Most people with the disease die of respiratory failure. There are currently no cures for ALS, nor effective treatments for slowing progression of the disease.

The companies are also investigating applying Sangamo’s gene therapy to frontotemporal degeneration, or FTD, a progressive neurodegenerative disease affecting the frontal and temporal lobes of the brain. FTD is marked by a gradual decline in behavior or language, similar to dementia, but usually not affecting memory. People with FTD often find it difficult to plan or organize activities, engage in social interactions, behave appropriately in professional situations, or care for oneself. Like ALS, there are no effective treatments for this disorder.

Sangamo develops therapies targeting specific genes for editing, silencing, or regulation using a process known as zinc-finger nucleases, where synthetic enzymes modify DNA sequences, including corrections or insertions. These enzymes, with a hydrocarbon and zinc chemistry, branch out in finger-like protrusions that bind with DNA molecules. Sangamo says it engineers the proteins to predictably and consistently bind with longer DNA sequences.

In this case, the companies are investigating Sangamo’s zinc finger transcription factors, engineered proteins designed to suppress mutations in the C9ORF72 gene. The C9ORF72 gene produces proteins found in motor neurons, as well as the brain and spinal cord, associated with sending and receiving signals from other nerve cells. Mutations in this gene are linked to ALS, particularly accumulations of proteins that impair normal cell functions and promote the death of nerve cells.

Sangamo says its zinc finger transcription factors bind to precise sequences of DNA, in this case, mutations of the C9ORF72 gene. The engineered proteins then suppress expression of that mutation. The companies plan to address a particular challenge in this strategy, namely differentiating between healthy and mutated forms of the gene, so only the mutation is suppressed.

Under the agreement, Sangamo is responsible for development of zinc finger transcription factor treatment-candidates for ALS and FTD. Pfizer will then conduct further research, development, manufacturing, and commercialization to take the candidates to market. Sangamo is receiving an initial payment of $12 million from Pfizer, and will be eligible for up to $150 million in subsequent payments tied to development and commercialization milestones, as well as royalties on sales of products from the collaboration.

This is not the first partnership between Sangamo and Pfizer. In May 2017, the companies began a collaboration on gene therapies to treat hemophilia A.

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Disclosure: The author owns shares in Pfizer.

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