Cystic Fibrosis (CF) is the most common fatal inherited genetic disease in Canada, affecting over 4300 Canadians, roughly 1 in 3850 births. CF impacts multiple organ systems, but the primary cause of mortality is recurrent airway infection and inflammation that progressively destroys the lungs. Tragically, half of those who died in the past year were under the age of 39.
However, there is hope for some, thanks to the drug Trikafta, which is improving the health and quality of life for CF patients with the most common CF mutation. CF can also be caused by hundreds of other, rare mutations. Some of these mutations will benefit from drugs like Trikafta, and some will not. The challenge lies in assessing the drug’s efficacy for these rare mutations, where there may be only a handful of individuals worldwide with some of these variations, making traditional clinical trials unfeasible.
In the United States, the Federal Drug Agency (FDA) expanded Trikafta’s approval to cover a subset of rare mutations that displayed potential benefits based on laboratory findings, without conducting clinical trials on individuals with these rare mutations. If Health Canada were to follow suit and broaden Trikafta’s approval to encompass this group of mutations, nearly 200 Canadians could access this life-saving drug. To date, Health Canada has not shown willingness to consider this type of evidence, and the drug manufacturer has not submitted the necessary data. Consequently, these 200 Canadians, who would have access to this life-saving drug if they resided in the United States, wait and grow sicker, and some will die. Canadians with other rare mutations not yet studied and approved in countries like the US may also benefit from Trikafta, so further study for these people is needed. Some rare mutations will not benefit from Trikafta and will instead need new types of therapies.
Cystic Fibrosis Canada is funding research and healthcare programs focused on CF and advocating for all members of the CF community, including those with rare mutations. We are funding Dr. Amy Wong, a promising early career researcher, who is leading the world in the development and refinement of methods for generating a variety of 2D and 3D lung models from stem cells. Researchers need a large source of lung cells and tissues to research new CF treatments, but such sampling is invasive and difficult for CF patients with already poor lung function. Dr. Wong’s stem cell-based lung models can help. These lung tissue models are genetically identical to the lungs of individual patients but can be generated as needed from their banked stem cells (sourced from a single blood draw) without invasive airway procedures. Currently, models such as rat cells or patient nasal cells are used as surrogates to evaluate patient lung response to Trikafta. Dr. Wong’s models could be used to show the response for each patient with a rare mutation in actual lung cells. These models are also being used to help develop genetic-based therapies that hold the promise to treat all people with CF, regardless of mutation.
Cystic Fibrosis Canada is a Member of Research Canada: An Alliance for Health Discovery and a Sponsor of the Parliamentary Health Research Caucus Morning Panel and Luncheon, Breakthrough Stem Cell Research & the Power of Regenerative Medicine. Visit rc-rc.ca to learn more.