On April 15, the newspaper Le Devoir published three articles on gene therapy to which Dr. Jacques P. Tremblay, researcher of our scientific committee, talks about the progress of this treatment. These three papers describe gene therapy, scientific advances, economic needs and opportunities for Quebec in relation to the development of viral vectors, as well as encouraging cases of patients who have received this treatment.

We invite you to consult these three articles, which make this complex therapy accessible to all, in order to better understand how close we are to a treatment for several hereditary diseases, including Friedreich’s ataxia.

In addition, these articles will provide the reasons why Ataxia Canada is raising funds for Dr. Jacques P. Tremblay’s promising research.

The first article,  Des thérapies géniques «made in» Québec, talks about the development of gene therapy in Quebec. See the short summary below:

Quebec researchers would like to test the innovative gene therapies developed in their laboratory with human subjects, but they must buy the viral vectors necessary for clinical studies from foreign companies at astronomical prices. Since the National Research Council of Canada (NRC) has a program for viral vectors for gene therapy in the last twenty years, Quebec holds the knowledge and the expertise in the production of viral vectors.

Therefore, Quebec researchers care about the project to create a center to produce these vectors for gene therapy in Quebec. At the Maisonneuve-Rosemont Hospital, all the necessary infrastructures already exist at the Center of Excellence in Cell Therapy (CETC). This center was designed to allow the production of viral vectors, but at the time of its erection, funding was not sufficient to realize this section reserved for gene therapy.

With such a laboratory, our scientists argue that they could value their discoveries here and offer their patients the gene therapies at a lower cost. Only a few million dollars is needed to realize this project

Read the complete article here (available in French only)

The second article, La thérapie génique connaît un second souffle,  presents the case of Zak, a young boy of 14 months old with a severe combined immunodeficiency, who is treated with gene therapy. See the short summary below:

Last week, 14-month-old Zak underwent the final phase of his gene therapy at the University of California Los Angeles Medical Center (UCLA). This treatment is expected to permanently cure Zak of his severe combined immunodeficiency, a genetic disease which threatened his life since his birth. Confident and hopeful, his parents already dream of the normal life that their child could finally have. If the treatment succeeds, Zak would now attend the day care center, have fun with other kids of his age, and his parents would finally sleep more serenely.

To get there, they had to go to California, where there is an experimental treatment in gene therapy. A therapy that is still not available in Quebec, despite the presence of researchers at the leading edge of gene therapy and the infrastructures that would make it available.

Gene therapy currently has the wind in its sails. Including in Quebec, the development of therapies that aims curing various incurable genetic diseases, even cancer, abounds. This dynamism follows a rather dark period of this research sector.

In the first clinical trials of gene therapy for severe combined immune deficiency in France (1999-2000), several children developed leukemia following treatment and one of them died. At the same time, in the United States, an 18-year-old boy succumbed to the side effects of gene therapy, which involved inserting a functional copy of a defective gene into his liver cells that prevented his body from eliminating ammonia produced during protein metabolism.

Armed with new and more reliable viral vectors, researchers have finally resumed clinical studies to test gene therapies for various genetic diseases. With encouraging results, projects to tackle other diseases and even cancer are abundant, especially here in Quebec.

Read the complete article here (available in French only)

The third article, Techniques d’administration de la thérapie génique,  explains how gene therapy works and how it will evolve in the coming years. See the short summary below:

Gene therapy aims to restore the function of the gene carrying a mutation. To do this, a normal copy of the mutated gene is inserted into the genome of the affected cells. Soon, the defective gene will be repaired with the famous CRISPR / Cas9 system.

Currently, gene therapy can only be considered for diseases caused by a mutation that prevents the functioning of the gene in which it is located. In such cases, the mutated gene does not produce enough, or not at all, the protein that it should normally provide to the body. To increase the production of the protein, the therapy will introduce a normal copy of this gene into the cells of the affected tissues which will compensate for the deficient gene. To ensure delivery of this normal copy of the gene, viruses that have been attenuated and lost their ability to replicate are used.

In 2000, Dr. James Wilson of the Rose H. Weiss Orphan Disease Center of the Perelman School of Medicine at the University of Pennsylvania discovered the family of adeno-associated viruses (AAV), which infect all humans without making them sick.

In the near future, the approach that will be adopted will be microsurgical and will repair the mutation present in the gene. This approach uses the CRISPR / Cas9 system which has not yet been tested with human subjects. This technique has the power to cut the DNA strands of the genome in very precise places if it has benchmarks in the form of a small RNA guide.

For which diseases?

Various monogenic diseases such as:

Immune deficiencies, including severe combined immunodeficiency (SCID)

Diseases of hemoglobin, such as beta-thalassemia and sickle cell disease or sickle cell anemia;

The deficiency of coagulation, including hemophilia B;

Liver diseases, including hepatorenal hereditary tyrosinemia and familial hypercholesterolemia;

Diseases of the retina, such as retinitis pigmentosa;

Pathologies affecting the brain or motor neurons that control muscle contraction, including Friedreich’s ataxia, Duchenne muscular dystrophy, spinal muscular atrophy, and some forms of lateral amyotrophic sclerosis (ALS).

Read the complete article here (available in French only)