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From diagnosis to novel gene therapy treatment in three years: Proof of alternative forms

In 2019, a one-year-old named Michael Pirovolakis received his initial diagnosis of the an ultra-rare condition SPG50 (or spastic paraplegia type 50) after having had whole genome sequencing. SPG50 is a progressive neurodegenerative disorder that causes developmental delays, speech impairments, seizures, a progressive paralysis of all four limbs, and may also be fatal ( ). According to article from Toronto’s SickKids Hospital, it is “believed there are approximately 80 children around the world with SPG50, making the condition an “ultra-rare disease”.

On March 24th, 2022, just three years after his initial diagnosis, Michael received a novel gene therapy to correct the disease-causing variants in a gene called AP4M1.

The incredible story of Michael’s journey, and the scientific and organisational developments that lead to his treatment, is a long one ( ). It involves a huge range of institutional players as well as dozens (if not one hundred) different dedicated physicians, researchers, regulators, administrators and hospital staff (see Figure 1 from CureSPG50 below).

Figure 1 – Collaborating institutional partners involved with bringing novel gene therapy to correct disease-causing variants in a gene called AP4M1

This is an incredible development, which is relevant to social pharmaceutical innovation (SPIN) in many ways.

To be sure, one-off treatments can be a success. A life is saved or changed and a patient has a higher quality of life. More than that, family members and carers are less burdened and stressed and experience an improvement in their quality of life as well. However, as Dr. David Malkin (Co-Lead, Precision Child Health, Director of the Cancer Genetics Program and the CIBC Children’s Foundation Chair in Child Health Research at SickKids in Toronto) points out, their initiative is not just about one patient but a platform, or bio-pharma ecosystem, that can do this for many other patients like Michael who are afflicted with other rare diseases:

“Successfully conducting the trial for Michael was not only a key milestone for him and his family but also for achieving SickKids’ vision for Precision Child Health, a movement to deliver individualised care for every patient,” says Dr. David Malkin. “Not only can rare diseases be a springboard to figure out how to treat more common conditions, but learnings from Michael’s trial will help carve out a path for SickKids to explore innovative, precision-based treatment options for other patients with rare, genetic diseases” (

This then becomes a key question for SPIN: how can individual successes be built out to broader system changes that benefit more patients? Can specific initiatives be scaled-up to produced more treatment for more patients, and if so how?

As we’ve already pointed out, such a social pharmaceutical ecosystem will require new forms of collaboration that simply have not existed previously, or the optimisation of pre-existing networks. This is work that we believe our consortia can contribute to, and/or participate in.

It will also require financial support. Michael’s parents fund-raised and crowd-sources millions of dollars to facilitate research and development for their son’s condition. While this is a significant achievement, it should not have to be this way. Drug discovery in general -and gene therapy in particular - is very expensive business, and it should not be up to families to foot the bill.

The provides excellent and highly transparent information. For instance their “Cost Breakdown” looks like this ( :

  • Proof Of Concept & Natural History Study = $400K USD

  • Raw Drug Material & Manufacturing = $1.5M USD

  • Safety Testing & Studies = $690K USD

  • Consulting & Other Costs = $82K USD

  • Donation & Credit Card Fees = 50K USD

  • Total Raised/Spent = $2.722M USD or $3.53M CDN

What is more, Michael’s parents point out that “although we raised enough money to create and manufacturer the drug for Michael – there are many more children with SPG50 that need to be treated. In order for us to be able to treat at least 10 more children we will need to raise US$250,000 per child to cover the 5 year study and hospital costs” (

The size of these kinds of financial commitments are unescapable; however, these numbers are likely to be much lower given that the treatment has been largely produced in the public sector, and operating under the umbrella of a trial.

Developing novel (gene) therapies for rare diseases is possible. The conventional idea that it takes 15 years and $2 billion dollars is false. Michael’s case has shown us what can be done with an incredible network of collaborators, patient activism, and a relatively modest amount of money (when compared to $2 billion). What is more, Michael’s case shows us that treatments can be developed within the public sector, and that the bio-pharma model/ industry does not have a monopoly on the development of treatments.

What is needed to move these kinds initiatives into the mainstream are policies and infrastructure that institutionalise network building, that finance R&D, and that can move beyond trial-based development strategies so that more - and future - patients can benefit. It is those kinds of policies and infrastructures that require our attention, and the research focus of our consortium.


Photo credit: Richard Catabay (2019). Group of people doing surgery [Image].


Written by: Dr. Conor Douglas

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