Gene therapies have experienced rapid development in recent years. However, these innovative treatments must be administered as early as possible to truly improve patients’ lives. But unfortunately, Quebec has fallen behind in neonatal screening for rare diseases against which this new technology could be greatly effective.
Since the first gene therapy trials, carried out in the 1990s on “bubble babies”, who suffered from a hereditary immune deficiency, this new therapeutic approach which consists of transferring to the patient a copy of the normal gene which, in him, is defective due to a mutation that evolved exponentially. An increasing number of gene therapies are being developed, tested or even available to meet the pressing needs of people suffering from rare diseases that are very debilitating and often fatal. In Canada, one in 12 people, or three million people in the country and 700,000 in Quebec, suffers from a rare disease, two-thirds of whom are children.
The advent of gene therapy has completely changed the work of Dr Nicolas Chrestian, researcher-clinician in pediatric neurology at the CHU de Québec-Université Laval. “This morning, I was performing a lumbar puncture to administer gene therapy to a young patient. Since the start of this treatment, this child has no longer needed to be hospitalized, so in the last four years. And he is significantly less stressed by the progression of his illness,” he reported Tuesday during an information session.
This young patient suffers from spinal muscular atrophy, a rare hereditary disease which is more prevalent in Quebec than elsewhere in Canada. It is a disease that causes the degeneration of motor neurons — which connect the spinal cord to the muscles — and, consequently, paralysis of the muscles, including those of swallowing and breathing.
Since 2019, patients who suffer from it have had access to gene therapy which consists of a single intravenous injection providing benefit for around fifteen years. However, this treatment must be administered very early in order to ensure the normal development of motor neurons during the first four years of life, hence the importance of early detection of the disease after birth. “When a patient already presents symptoms, it means that he or she has already lost neurons, and will do so forever. He will therefore have after-effects. Whereas if we treat the child very early, we can improve their quality of life, their vital prognosis, and avoid multiple hospitalizations. He will even be able to lead a normal life, and it will therefore cost society much less,” underlined the Dr Christian.
Gene therapies can be very expensive, in some cases reaching several million dollars. However, the benefits they provide to the patient and their family as well as to society by requiring much less care and hospitalizations outweigh these costs, several experts have affirmed.
Gene therapy is also available to treat people with hereditary retinal dystrophy, a visual impairment caused by a genetic mutation. And at least five companies have developed gene therapy for Duchesne muscular dystrophy. “These therapies have given very encouraging results at least in stabilizing patients who would otherwise be doomed to certain death in their twenties or thirties,” noted Dr.r Christian.
The general director of the Regroupement québécois des Maladies Orphanes, which defends the interests of patients suffering from a rare or orphan disease, indicated that the biggest problem facing these patients is diagnostic wandering. “A patient will on average spend between five and seven years and consult around fifteen specialists before we can accurately diagnose the disease that affects them,” explains Jonathan Pratt.
Screening for rare diseases in newborns (neonatal) would help hasten the diagnosis. “In Quebec, around twenty diseases can be screened for, but in Ontario and Alberta, the screening program is much more extensive, a greater number of diseases are subject to neonatal screening. If screening tests are available and other provinces use them, I don’t see why we don’t use them in Quebec, especially knowing how important it is to intervene as early as possible in these diseases, which are often degenerative. », argues Mr. Pratt.
Another problem patients face is the long interval between the approval of a new treatment by regulatory authorities and its administration to the patient. More than two years can pass, during which “patients [concernés] see their condition deteriorate and may even die,” laments Mr. Pratt.
For example, a gene therapy against hemophilia B received approval from Health Canada on December 27, but it will only be available to patients in two years.
The gene therapies that are currently the most advanced use associated adenoviruses that have been emptied of their content to deliver the desired gene into the body. But many patients have antibodies against these viruses, having already been exposed to them, which limits the proportion of patients who can receive this type of treatment. Scientists are currently exploring other types of vectors, including lipid nanoparticles similar to those used in the COVID-19 RNA vaccine.