Advancing Gene Therapy Research for a Devastating Rare Disease

28 September 2022

Mya, 13

Neurofibromatosis Type II (NF2) doesn’t debilitate people all at once. Patients may lose part of their hearing or vision or mobility, and there may be quiet stretches in-between. But what is certain is that their quality of life will continue to decline. “Things will become more complicated, each day that goes by. It’s just a terrible disease. It shows no mercy,” said Ontario resident Craig Gerlach, stepfather to NF2 patient Mya, 13 years old.

Myriad Canada is working with patient-led foundation NF2 BioSolutions to finance promising gene therapy research for NF2, with the hope it will lead to a cure for this rare genetic disorder and change the course of patients’ lives.

What is NF2?

NF2 is caused by a defective gene that is missing a protein needed to fight off tumors. The disease is characterized by the persistent growth of benign tumors along various nerves. These tumors typically appear on cranial nerves, along the spine and behind the eyes. They impinge on the surrounding nerves, causing deafness, blindness, facial palsy, head and leg pain, mobility issues and other debilitating conditions. The average age of death for NF2 patients is 36 years. Some patients die in adolescence or early adulthood due to complications from the disorder.

Up until now, the only options to extend functioning and life for NF2 patients have been surgery as well as certain treatments developed for cancer, such as chemotherapy and radiation. The delicate surgeries to remove NF2 tumors from the brain and spine require specialized expertise and carry great risk. The treatments used to slow down or shrink tumors come with heavy side effects and are not suited to long-term use. None can stop tumor growth all together. As is the case for other rare diseases, attracting interest and funding to support innovative research for NF2 is challenging.

Gilles and Sarit Atlan with their daughter Karen

Patients Mobilize to Find a Cure

Four years ago, Nicole Henwood, mother of a young boy with NF2, started NF2 BioSolutions together with other members of the patient community. The goal of the US-based foundation: to promote, facilitate and finance gene therapy research to cure NF2. NF2 is an ideal candidate for gene therapy research, as it is caused by a single defective gene. Gene therapy has the potential to replace the defective NF2 gene and put a healthy copy in its place, preventing future tumors. “We started with just a few families who had the dream of using these new technologies that are working in some other rare diseases similar to NF2, and having the same success,” explained Vice President Gilles Atlan, whose 14-year old daughter Karen suffers from NF2.

The organization brought together leading neurologists, geneticists and researchers to examine the leading gene therapy approaches. NF2 BioSolutions currently supports 10 top-tier research laboratories exploring three distinct gene therapy approaches and a unique bacteriotherapy approach for the treatment of NF2. “We brought a new vision of really being able to take care of the disease in the long term,” said Atlan. “For patients and their families, the fact that we can do something positive about it makes us able to live with that stress.”

Cutting-Edge Research at one of the Country’s Top Labs

Dr. Katherine Meyer

Since 2019, Myriad Canada has partnered with NF2 BioSolutions to fund an NF2 gene therapy pilot pre-clinical study at the Abigail Wexner Research Institute at Nationwide Children’s Hospital (NCH), renowned as “ground zero” for gene therapy research. NCH is where the first and only systematically administered gene therapy approved by the FDA was developed, for Spinal Muscular Atrophy (SMA). Thanks to Canadian donors, this study is investigating the gene addition approach to insert the functioning NF2 gene into mutant cells aimed to halt tumor growth and prevent future tumor formation.

Dr. Kathrin Meyer serves as the project’s principal investigator. Her lab has a strong translational focus, with the goal of moving to clinical trials within the near future. “We have a lot of experience in getting gene therapy to the clinic and doing so safely,” said Dr. Meyer. “And my team is extremely motivated and hardworking.” On behalf of Myriad Canada, NF2 BioSolutions is sponsoring two full-time researchers to work along with Dr. Meyer, focused solely on NF2 research.

Dr. Krizelle Alcantara

One of the project’s researchers, Krizelle Alcantara, is an NF2 patient herself. A molecular biologist, she has found purpose in studying her own disorder. Before relocating to Ohio to join Dr. Meyer’s team, Alcantara was the NF2 BioSolutions Ambassador for the Philippines, reaching out to the patient community. “I saw these people and I came to know them beyond having NF,” she told NF2 BioSolutions. “They are very resilient, very strong-willed people battling the same disorder that I have. Something has to be done, and I realized that I am in a position to actually do something.”

Despite the disease’s growing impact on her life, Alcantara is driven to persevere in her work, as well as inspiring her team. “We’ve worked with a lot of patient foundations very closely, but seeing it every day, it gives me a lot of respect for the patients because they don’t have a choice,” said Dr. Meyer, who adds that patients have been instrumental to pursuing new treatments for NF2. “They’re not only fundraising, they’re also donating their skin and blood and taking part in clinical trials, and oftentimes they know it’s not for them, it’s for the future. They’re putting themselves on the line to move this forward. They are the real heroes.”

Racing Against Time

Today NF2 patients and families can be assured that the best gene therapy researchers are working to find a cure for NF2. Dr. Meyer’s lab actively shares its findings with the medical research community. Breakthroughs work to accelerate not only treatments for NF2, but also for other genetic disorders. “Everything we do we can have an impact, every milestone that we achieve,” said Atlan. “Every researcher that is working on it is getting experience and shares these experiences with others.”

Jon Kantor

The next challenge on the horizon is to prepare for clinical trials, which will require a significant amount of funding. NF2 BioSolutions and Myriad Canada are working to raise awareness of NF2 and rally people to support the push for a cure. “Fundraising is really so important,” said Dr. Meyer. “It makes a huge difference in the patients’ lives to know that people are helping and supporting and fundraising for these diseases, because sometimes they can feel very lonely.”

Isolation is a particular challenge for the patient community dispersed across the vast expanse of Canada, NF2 patient Jon Kantor of Montreal points out. Several of his family members suffer or have died from complications of NF2. Kantor helped facilitate the partnership with Myriad Canada, which has made it easier for more Canadians to contribute. “I know it’s a long haul and I or my children may not derive any benefit. But we hope it will help other people,” he said.

It is this hope that keeps patients like Mya and their families going, said Gerlach: “You can dream that one day, in her lifetime, it will have a positive impact on her, and maybe make her life better.”

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