“Now that we have seen in the laboratory that our gene therapy works against Pompe disease, we are going to test it in people with the disease for the first time,” says researcher Pim Pijnappel. In May of this year, he was appointed Professor of Cell and Gene Therapy at Erasmus MC. He explains how many steps still need to be taken before the first patient in his study receives the one-time treatment intended to halt the muscle disease. “Applying for permits, scraping together funding, designing the study, determining which effects we will measure, taking safety criteria into account, and turning it into a product that meets all requirements before we give it to patients.”
Erasmus MC already has the knowledge and the patients, but bringing a gene therapy to market is a different matter. “That is a complex process, involving many aspects and requiring a lot of money. And if our research succeeds, we want to make the therapy available as quickly as possible at an affordable price for as many patients as possible. Because we as researchers have no experience with this, LentiCure was established.”
An indispensable link
LentiCure director Dirk van Asseldonk describes himself as a bridge builder. “After twenty years of entrepreneurship in traditional companies, I am highly motivated to change the business model for drug development. Instead of a company with shareholders who expect to earn at least twenty times their investment back, we want to use public funding to realize a therapy with a socially responsible price.”
He sees LentiCure as an indispensable link in the further development of gene therapy for Pompe disease. “To be able to treat the first patient with it in about two years, the production process must meet all kinds of quality requirements in the areas of safety, effect measurement, product control, and regulation. We are now going to find and map out the best route for that.”
A new step
“This is the first time that we are working together with scientists and entrepreneurs on the production of a gene therapy for Pompe disease,” says Ellen Sterrenburg, director of the Prinses Beatrix Spierfonds. The fund entered into the collaboration with Erasmus MC and LentiCure last May. “After subsidizing the scientific research into this gene therapy since 2019, together with Erasmus MC we felt the time was now right for a new step. We hope that this one-time therapy can address the cause of Pompe disease with a long-lasting effect, including on the brain. So that the deterioration can truly be stopped and, in the most ideal case, the disease can be prevented.”
Not unusual
“At Erasmus MC, we want to make the best care accessible to as many people as possible. That is why we also want to contribute to further developing the discovery of Pim Pijnappel and his team for Pompe disease,” says Stefan Sleijfer, Chair of the Executive Board and Dean of Erasmus MC. “How great would it be if people with Pompe disease, instead of weekly or biweekly infusions, could be helped long-term with a single treatment? That would be far less burdensome for patients and for healthcare.”
Although Erasmus MC now hopes to have found such a therapy, much still needs to be done before it becomes available to patients. “We do not receive government funding for this expensive development work, which is why we are collaborating with the Spierfonds in LentiCure.” Such a solution is not unusual for Erasmus MC. “We have various arrangements to bring our discoveries to patients as quickly and safely as possible. Our goal is also to do so at a socially responsible price.”
Additional criteria
The Spierfonds had LentiCure’s business plan assessed in advance and submitted it to the scientific advisory board for approval. Once all the lights were green, the founding statutes of LentiCure laid down how the subsidy may be spent and how accountability must be provided. “In addition to our standard procedures for scientific research, in this case we also assess extra criteria for production, safety, and regulation,” explains Ellen Sterrenburg.
In the agreed division of roles around LentiCure, the Spierfonds will not only act as a financier, but also work to increase the confidence of external parties in this approach. “We have never been so hopeful and see it as our task to share this expectation with other European muscle disease funds, so that even more support will come for this initiative.”
"The time is ripe for a new step – Ellen Sterrenburg"
A major challenge
If research in the first patients with Pompe disease shows that the gene therapy works, Pim Pijnappel hopes to also apply it to two brain diseases caused by the absence of certain enzymes. “Subsequently, we will probably be able to use the therapy for other muscle diseases without many modifications. By focusing on Pompe disease now, we hope to accelerate the treatment of more muscle diseases.”
Stefan Sleijfer expects that, if successful, the LentiCure model will be adopted by other university medical centers. “We share the same mindset. We all want the best for the patient, but that is a major challenge in this day and age. That is why I can imagine that companies like LentiCure will need even more investors to ensure that new therapies meet all quality requirements and are effective. That research costs a lot of money. But I expect that, in addition to the Spierfonds, more organizations and private individuals will be willing to invest in this without seeking profit.”
The Prinses Beatrix Spierfonds and gene therapy
In 2020, the Spierfonds launched the Gene Therapy Research Program. Developments in gene therapy are progressing at lightning speed. This makes now the ideal moment to apply this promising technique for people with hereditary muscle diseases—in the Netherlands, so that Dutch patients are the first to benefit and so that we retain control over the affordability of potential medicines.
The research program started with studies into three diseases: myotonic dystrophy, Duchenne muscular dystrophy, and Pompe disease. Research is now also underway into gene therapy for FSHD, HMSN, mitochondrial myopathy, and nemaline myopathy. This has further strengthened the program. The investment in LentiCure is also an important part of the program, aimed at ensuring—together with all parties involved—that promising gene therapies become available to all patients.
"A one-time treatment would be far less burdensome for patients and for healthcare – Stefan Sleijfer"
Spierziekten Nederland on LentiCure
Spierziekten Nederland supports the start-up LentiCure and contributes in various ways to make the initiative a success. “As a patient organization, we believe it is important that affordable medicines are and remain available for people with a muscle disease,” explains Marcel Timmen of Spierziekten Nederland. “We have been closely involved for a long time in the development of gene therapy for Pompe disease and also have a longstanding relationship with Erasmus MC. Together with the Prinses Beatrix Spierfonds, we also advocated for the appointment of Pim Pijnappel as endowed Professor of Cell and Gene Therapy at Erasmus MC. The fact that gene therapy for Pompe is now being developed through LentiCure all the way to hospital treatment via a non-commercial route is important. This helps to ultimately keep the therapy affordable and bring it to market at a socially responsible price. This approach also provides greater transparency in costs.”
