Sangamo and Pfizer to Collaborate on Developing Gene Therapies for ALS

Sangamo and Pfizer to Collaborate on Developing Gene Therapies for ALS

Sangamo Therapeutics and Pfizer will work together on gene therapies they hope will overcome mutations that cause ALS and frontotemporal lobar degeneration.

Gene therapy works by delivering a healthy copy of a malfunctioning gene to a patient.

The therapy that Sangamo is developing replaces a faulty C9orf72 gene. It consists of a zinc finger protein engineered to bind to a particular DNA sequence in the gene. The binding suppresses the abnormal gene.

A major challenge in gene therapy is ensuring that an engineered protein can regulate a faulty gene’s production of protein needed for normal functioning. If the gene produces too little or too much protein, the body continues to be susceptible to the disease that the replacement gene was designed to eliminate.

Sangamo has come up with a new way to achieve the proper regulation of a gene’s protein production.

It involves transcription factors, proteins that can maintain or turn off a gene’s production. Some transcription factors signal that a gene’s activity should continue. Others signal that it should be shut down.

Zinc finger protein transcription factors, or ZFP TFs, are the most common transcription factors that bind to DNA.

Sangamo attached a zinc finger protein that targets a specific DNA sequence to a particular transcription factor. This approach means that the therapy can either maintain a gene’s activity or shut it down, depending on which is necessary.

The partners hope the technology can treat neurodegenerative disorders such as ALS and frontotemporal lobar degeneration that stem from C9orf72 gene mutations. It would do this by preventing the mutated C9orf72 gene from generating faulty protein.

Sangamo and Pfizer want to develop ZFP-TFs that can differentiate between the faulty C9orf72 gene and a normal one, repressing only the mutant form.

“The precision and flexibility of zinc finger proteins enables targeting of virtually any genetic mutation,” Sandy Macrae, chief executive officer of Sangamo, said in a press release.

Under their agreement, Sangamo will be responsible for coming up with ZFP-TF candidates. Pfizer will be responsible for research, treatment development, manufacturing, and commercialization of any gene therapies Sangamo creates. Sangamo will receive a $12 million upfront payment from Pfizer as part of the deal.

The C9orf72 mutation is thought to be associated with 25 to 40 percent of all inherited cases of ALS. Some people with the mutation experience both movement and dementia problems.

Sangamo is also developing ZFP-TFs to treat central nervous system diseases. And it is working on a way to regulate the production of tau, a protein associated with Alzheimer’s disease and frontotemporal dementia.


  1. Julio Pina says:

    For every sort of god’s sake, I’m ready for it! I need to know when the treatment will be available to us as soon as possible! Please! The first studies! Anything!

  2. Charlie says:

    Huge rise in Sangamo’s stock price on this announcement on Wednesday.
    $12 million bucks upfront for Sangamo with a possibility of a further $150 million bucks if it meets developmental and commercial milestones.
    Why am I thinking….another Radicava gold seam.

    This research is focused on the C9orf72 gene associated with a third of INHERITED ALS cases. That’s only about 5% of ALL als cases.

    It would serve pALS better,statistically, if a commonality was pursued for the other 2/3ds of inherited cases; even better, a commonality of gene-malfunction experienced by ALL pALS.

    But ‘business is business.’

    • Ron H Fovargue says:

      Agree and understand, consider this, it is ‘a start’ and from this success other therapies will then follow. It also is a ‘revenue source’, ugly as that sounds, there has to be a financial win to encourage continued development. Respectfully, R H Fovargue

      • Charlie says:

        Many ‘exciting’ research projects in the lab are being funded from charitable donations. (Think Ice Buckets, and cold wet heroes and heroines.) Big Pharma will usually step in only when something looks reasonably promising, and not before. Now think Radicava and $146,000 per year per treatment.
        Pfizer are no mugs. They can see that gene-therapy is the cleanest dirty shirt in the laundry of research possibilities.
        Keep eyes peeled over the next few years for patent applications and Radicava-style price lists.
        The best hope for CURRENT pALS is still a huge surprising and serendipitous piece of luck in the lab.

      • Charlie says:

        ‘…and from this success other therapies will then follow…’

        Nothing followed Riluzole for 20 years.

        I admire your optimism.I hope you are right.

  3. Charlie says:

    Not a single word in the article as to trialling so this currently looks like a drawing-board and petrie-dish concept, to me.

    If they committed to trialling from here I would suggest 6-7 years before Rx stage- assuming something works with reasonable efficacy. Let’s not forget that this is aimed at the sector of pALS who have the inherited form. So 95% of all pALS are not, at this stage anyway, candidates.

    • Charlie says:

      “Thus, at this time, ALSUntangled does not recommend the Deanna Protocol to patients with ALS. Before it can be recommended, a reproducible version of the Deanna Protocol should be shown to influence plausible physiologic mechanisms such as central nervous system ketone bodies, as well as clinically meaningful outcome measures such as ALSFRS-R and FVC in patients with ALS.”

  4. Ana says:

    It’s been 25 yrs since my father passed of ALS the C9orf72 gene now my brother is dying of the same C9orf72 what the hell is taking so long?? Please help my brother Julio ASAP anything! The first study! Please!

  5. Patrick Revere says:

    Therapies specific to a gene mutation represent the open door to other mutations, random forms of the disease (which are increasingly likely to be assigned to some mutation) as well as therapies for other associated NMDs like Parkinsons and other genetic flaws like Cystic Fibrosis. C9 is a start that may well work for massive numbers of people around that mutation.

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