Category Archives: Gene Medicine

A study of some of the sickest COVID-19 patients, such as those placed on ventilators, has identified gene variants that put people at greater risk of severe disease.

By Jocelyn KaiserOct. 13, 2020 , 1:25 PM

Sciences COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

Its one of the pandemics puzzles: Most people infected by SARS-CoV-2 never feel sick, whereas others develop serious symptoms or even end up in an intensive care unit clinging to life. Age and preexisting conditions, such as obesity, account for much of the disparity. But geneticists have raced to see whether a persons DNA also explains why some get hit hard by the coronavirus, and they have uncovered tantalizing leads.

Now, a U.K. group studying more than 2200 COVID-19 patients has pinned down common gene variants that are linked to the most severe cases of the disease, and that point to existing drugs that could be repurposed to help. Its really exciting. Each one provides a potential target for treatment, says genetic epidemiologist Priya Duggal of Johns Hopkins University.

In a standard approach to finding genes that influence a condition, geneticists scan the DNA of large numbers of people for millions of marker sequences, looking for associations between specific markers and cases of the disease. In June, one such genomewide association study in The New England Journal of Medicine (NEJM) found two hits linked to respiratory failure in 1600 Italian and Spanish COVID-19 patients: a marker within the ABO gene, which determines a persons blood type, and a stretch of chromosome 3 that holds a half-dozen genes. Those two links have also emerged in other groups data, including some from the DNA testing company 23andMe.

The new study confirmed the chromosome 3 regions involvement. And because 74% of its patients were so sick that they needed invasive ventilation, it had the statistical strength to reveal other markers, elsewhere in the genome, linked to severe COVID-19. One find is a gene called IFNAR2 that codes for a cell receptor for interferon, a powerful molecular messenger that rallies the immune defenses when a virus invades a cell. A variant of IFNAR2 found in one in four Europeans raised the risk of severe COVID-19 by 30%. Baillie says the IFNAR2 hit is entirely complementary to a finding reported in Science last month: very rare mutations that disable IFNAR2 and seven other interferon genes may explain about 4% of severeCOVID-19 cases. Both studies raise hopes for ongoing trials of interferons as a COVID-19 treatment.

A more surprising hit from the U.K. study points to OAS genes, which code for proteins that activate an enzyme that breaks down viral RNA. A change in one of those genes might impair this activation, allowing the virus to flourish. The U.K. data suggest there is a variant as common and influential on COVID-19 as the interferon genetic risk factor.

Other genes identified by Baillies team could ramp up the inflammatory responses to lung damage triggered by SARS-CoV-2, reactions that can be lethal to some patients. One, DPP9, codes for an enzyme known to be involved in lung disease; another, TYK2, encodes a signaling protein involved in inflammation. Drugs that target those two genes proteins are already in useinhibitors of DPP9s enzyme for diabetes and baricitinib, which blocks TYK2s product, for arthritis. Baricitinib is in early clinical testing for COVID-19, and the new data could push it up the priority list, Baillie says.

The chromosome 3 region still stands out as the most powerful genetic actor: A single copy of the disease-associated variant more than doubles an infected persons odds of developing severe COVID-19. Evolutionary biologists reported last month in Nature that this suspicious region actually came from Neanderthals, through interbreeding with our species tens of thousands of years ago. It is now found in about 16% of Europeans and 50% of South Asians.

But the specific chromosome 3 gene or genes at play remain elusive. By analyzing gene activity data from normal lung tissue of people with and without the variant, the U.K. team homed in on CCR2, a gene that encodes a receptor for cytokine proteins that play a role in inflammation. But other data discussed at last weeks meeting point to SLC6Z20, which codes for a protein that interacts with the main cell receptor used by SARS-CoV-2 to enter cells. I dont think anyone at this point has a clear understanding of what are the underlying genes for the chromosome 3 link, says Andrea Ganna of the University of Helsinki, who co-leads the COVID-19 Host Genetics Initiative.

The U.K. genetics study did not confirm that the ABO variants affect the odds of severe disease. Some studies looking directly at blood type, not genetic markers, have reported that type O blood protects against COVID-19, whereas A blood makes a person more vulnerable. It may be that blood type influences whether a person gets infected, but not how sick they get, says Stanford University geneticist Manuel Rivas. In any case, O blood offers at best modest protection. There are a lot of people with O blood that have died of the disease. It doesnt really help you, says geneticist Andre Franke of the Christian-Albrecht University of Kiel, a coleader of the NEJM study.

Researchers expect to pin down more COVID-19 risk genesalready, after folding in the U.K. data plumbed by Baillies team, the COVID-19 Host Genetics Initiative has found another hit, a gene called FOXP4 implicated in lung cancer. And in a new medRxiv preprint posted last week, the company Ancestry.com reports that a gene previously connected to the effects of the flu may also boost COVID-19 susceptibility only in men, who are more likely to die of the disease than women.

Geneticists have had little luck so far identifying gene variants that explain why COVID-19 has hit Black people in the United States and United Kingdom particularly hard. The chromosome 3 variant is absent in most people of African ancestry. Researchers suspect that socioeconomic factors and preexisting conditions may better explain the increased risks. But several projects, including Baillies, are recruiting more people of non-European backgrounds to bolster their power to find COVID-19 gene links. And in an abstract for an online talk later this month at the American Society of Human Genetics annual meeting, the company Regeneron reports it has found a genome region that may raise the risk of severe disease mainly in people of African ancestry.

Even as more genetic risk factors are identified, their overall effect on infected people will be modest compared with other COVID-19 factors, Duggal says. But studies like the U.K. teams could help reveal the underlying biology of the disease and inspire better treatments. I dont think genetics will lead us out of this. I think genetics may give us new opportunities, Duggal says.

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Found: genes that sway the course of the coronavirus - Science Magazine

ROCKVILLE, Md., Oct. 13, 2020 /PRNewswire/ --Foundation to Fight H-ABC, a non-profit organization dedicated to increasing awareness and driving development of a cure for the degenerative children's disease, H-ABC, today announced a sponsored research agreement with the University of Massachusetts Medical School and Yale University to advance a targeted gene therapy for H-ABC.

"We have high hopes to quickly prove efficacy with this approach to move research forward and find a permanent cure for this devastating disease," said Michele Sloan, Co-Founder, Foundation to Fight H-ABC.

H-ABC (hypomyelination with atrophy of the basal ganglia and cerebellum) belongs to a group of conditions called leukodystrophies, diseases that affect the white matter of the brain. These diseases disrupt the growth or maintenance of the myelin sheath, a protective layer that insulates nerve cells and allows for the transmission of messages between cells.

Caused by a mutation in the TUBB4A gene, H-ABC is a rare genetic disorder that affects certain parts of the brainspecifically the basal ganglia and the cerebellum, which control movement. H-ABC targets these important structures, reducing both their size and function. As a result, children who suffer from H-ABC often experience motor problems, cannot walk, talk, or sit on their own. Currently, there is no known cure for this disabling and life-threatening condition.

The teams of Dr. Guangping Gao (University of Massachusetts Medical School) and Dr. Karel Liem (Yale School of Medicine) will combine extensive expertise in the fields of Adeno-associated virus (AAV), a platform for gene delivery for the treatment of a variety of human diseases and H-ABC disease models, to develop AAV vectors to silence or outcompete the mutated TUBB4A gene.

"To date, AAV-based gene delivery system is the vector of choice for in vivo gene therapy of many currently untreatable rare diseases including H-ABC," said Guangping Gao, Ph.D. "We are very excited for starting close collaborations with Dr. Liem's team at Yale and the Foundation to Fight H-ABC to develop potential gene therapeutics for this devastating disease."

"With the support from the Foundation to Fight H-ABC, we are excited to build upon our mechanistic studies of the disease and to collaborate with Dr. Gao of the University of Massachusetts to develop and test AAV approaches to H-ABC," saidKarel F Liem Jr., M.D., Ph.D.

For more information, please visit https://www.h-abc.org/donate.

CONTACT: Sawyer Lipari, [emailprotected]

SOURCE Foundation to Fight H-ABC

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Foundation to Fight H-ABC, University of Massachusetts Medical School and Yale University Initiate Gene Therapy Study Targeting Cure for Rare Disease...

Inherited retinal dystrophies (IRDs) are a group of blinding conditions caused by mutations in more than 270 different genes, including the RPE65 gene3. RPE65-mediated IRDs often disproportionally affect children and young adultsand cause progressive vision loss, leading to complete blindness in almost all patients2. Luxturna is designed to provide functioning copies of theRPE65gene to act in place of mutatedRPE65genes2.These functioning genes produce the RPE65 protein to help improve vision and prevent progression towards total blindness2.

"The effects of RPE65-mediated inherited retinal diseases can be life-changing. Previously, there was no treatment available and the progression towards complete blindness was inevitable." said Dr. Elise Hon, an Ophthalmologist in the Department of Ophthalmology and Vision Sciences and the Director of the Eye Genetics Program at The Hospital for Sick Children (SickKids) in Toronto. "This approval is a very important step forward in the treatment of genetic eye disorders."

Due to the highly specialized nature of the therapy, Novartis is collaborating with key centres and their multidisciplinary teams to deliver Luxturna to patients across Canada: SickKids in partnership with Sunnybrook Health Sciences Centre in Ontario, and Montreal Children's Hospital, McGill University Health Centre in partnership with Maisonneuve-Rosemont Hospital (HMR), Centre intgr universitaire de sant et de services sociaux (CIUSSS) de l'Est-de-l'le-de-Montral, affiliated with Universit de Montral in Quebec.

"Being part of tremendous innovations in the treatment of certain eye conditions over the past decades has been incredibly rewarding. Gene therapy heralds the start of a new era for IRDs and I'm thrilled to be part of this historic moment and equally excited to be able to give patients a chance to regain sight with Luxturna," said Dr. Peter Kertes, retina surgeon and Ophthalmologist-in-Chief, Sunnybrook Health Sciences Centre and staff ophthalmologist at SickKids in Toronto.

The current standard of care for people born with IRDs caused by RPE65 gene mutations is supportive in nature and focuses on monitoring, psychological support, mobility training and visual rehabilitation4. Until now, no pharmacological treatment option was available to treat the underlying disease mechanism or alter the natural history of inherited retinal dystrophies. While a genetic test is needed to confirm that vision loss is caused by mutations in theRPE65gene2, it can be a lengthy process to access testing and counselling. Novartis has entered into a partnership with Blueprint Genetics to help facilitate genetic testing where appropriate in order to validate the diagnosis.

"The approval of the first gene replacement therapy for Canadians is historical. We have been waiting for this moment in the vision community for decades. To be able to tell a parent that their child's impaired sight could now be restored or improved is remarkable,' said Doug Earle, President & CEO of Fighting Blindness Canada. "We welcome this medical innovation and hope that Canadians in need of this therapy have access to it without delay."

"Novartis is proudly reimagining medicine by bringing forward innovations like Luxturna. Today's approval will have a significant impact on patient care," said Andrea Marazzi, Country Head, Novartis Pharmaceuticals Canada. "We are grateful to the vision community for rallying behind Canadians who are impacted by vision impairment and vision loss and we are committed to helping them gain access to this game-changing gene therapy as quickly as possible."

AboutRPE65mutation-associated inherited retinal dystrophyMutations in both copies of theRPE65gene affect approximately 1 in 200,000 people and can lead to blindness5,6. Early in the disease patients can suffer from night blindness (nyctalopia), loss of light sensitivity, loss of peripheral vision, loss of sharpness or clarity of vision, impaired dark adaptation and repetitive uncontrolled movements of the eye (nystagmus)6. Patients with mutations in both copies of theRPE65gene may be diagnosed, for instance, with subtypes of either Leber congenital amaurosis or retinitis pigmentosa7.

About Novartis in Cell & Gene TherapyNovartis is at the forefront of cell and gene therapies designed to halt diseases in their tracks or reverse their progress rather than simply manage symptoms. The company is collaborating on the cell and gene therapy frontier to bring this major leap in personalized medicine to patients with a variety of diseases, including genetic disorders and certain deadly cancers. Cell and gene therapies are grounded in careful research that builds on decades of scientific progress. Following key approvals of cell and gene therapies by health authorities, new treatments are being tested in clinical trials around the world.

About Novartis in CanadaNovartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2019, the company invested $51.8 million in research and development in Canada. Located in Dorval, Quebec, Novartis Pharmaceuticals Canada Inc. employs approximately 1,500 people in Canada and is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. For further information, please consult http://www.novartis.ca.

About Novartis globallyNovartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 145 nationalities work at Novartis around the world. Find out more at http://www.novartis.com.

Luxturna is a registered trademark of Spark Therapeutics Inc., used under license by Novartis Pharmaceuticals Canada Inc.

References

1.

Novartis Pharmaceuticals Canada Inc. Luxturna(voretigene neparvovec) Product Monograph. October 13, 2020.

2.

Russell S et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65- mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. The Lancet 2017; 390:849-860

3.

RetNet. Summaries of genes and loci causing retinal diseases. Available at: https://sph.uth.edu/retnet/sum-dis.htm.

4.

National Institute for Health and Care Excellence (NICE). Voretigene neparvovec for treating inherited retinal dystrophies caused by RPE65 gene mutations [ID1054]2018:199/799

5.

Novartis. Data on file. 2018.

6.

Astuti GD et al. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark. European Journal of Human Genetics 2016; 24: 107179.

7.

Morimura H et al. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis. Proceedings of the National Academy of Sciences of the USA. 1998; 95: 308893.

SOURCE Novartis Pharmaceuticals Canada Inc.

For further information: Novartis Media Relations: Julie Schneiderman, +1 514 633 7873, E-mail: [emailprotected]

http://www.novartis.ca

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Health Canada approves first-ever gene replacement therapy, Luxturna - Canada NewsWire

Understanding genetic disease in mixed-breed and purebred dogs and cats can bring about more effective treatments and better client service, says clinical geneticist and general practitioner Dr. Jerold Bell.

If we understand the genetic background of our patients, were better positioned to prevent, to mitigate, or to alter the expression of genetic disease, allowing our patients to be healthier in their lifetimes as well as to breed healthier dogs and cats, Dr. Bell said.

An adjunct professor at the Cummings School of Veterinary Medicine at Tufts University, Dr. Bell spoke about genetic diseases during the AVMA Virtual Convention 2020 this August. In addition to his teaching duties, Dr. Bell works as a solo practitioner, and he sees dogs and cats all day long and sees genetic disease in our patients all day long.

He explained that common genetic disorders are caused by ancient disease liability genes that preceded breed formation. Since these mutations occurred long before the separation of breeds, these diseases are seen across all breeds and in mixed breeds.

The most common hereditary diseases in dogs are allergies, followed by hip and elbow dysplasia; inherited cancers such as lymphoma, hemangiosarcoma, mast cell tumor, and osteosarcoma; patella luxation; nonstruvite bladder stones; hypothyroidism; mitral valve disease; inflammatory bowel disease; diabetes mellitus; retained testicles; and umbilical hernias.

In cats, the most prevalent genetic diseases are inflammatory cystitis, then feline urological syndrome, diabetes mellitus, lymphoplasmocytic gingivostomatitis, nonstruvite bladder stones, allergies, eosinophilic skin disease, and inflammatory bowel disease.

Disease is not a function of homozygosity, which happens when identical DNA sequences for a particular gene are inherited from both biological parents, nor is it a consequence of inbreeding. Rather, Dr. Bell explained, hereditary diseases are a result of the accumulation and propagation of specific disease liability genes. Breed-related deleterious genes accumulate in various ways, including direct selection for disease-associated phenotypes, linkage to selected traits, carriage by popular sires, genetic drift, andmost importantlythe absence of selection against deleterious phenotypes.

If we dont select for healthy parents to produce offspring, then we have no expectation of health in those offspring, Dr. Bell said. Not selecting for health is selecting for disease, and we need to understand that and pass that on to our breeder clients.

On the topic of disease and extreme phenotypes, Dr. Bell said brachycephalic obstructive airway syndrome is frequently diagnosed at veterinary clinics on account of the popularity of certain brachycephalic dog breeds, namely Pugs, French Bulldogs, and Bulldogs. Most breed standards do not call for the expression of extreme phenotypes, he said, nor do they select for the most extreme size or the most extreme brachycephalic trait.

Moderation away from extremes that cause disease should be the guiding principle in breeding, Dr. Bell noted, and in judging dog shows.

Common genetic diseases seen in mixed-breed dogs and cats occur randomly because of dispersed ancient liability genes, according to Dr. Bell. Uncommon and breed-specific recessive or complexly inherited disease is far less likely to occur in mixed-breed individuals.

Dr. Bell said designer-bred dogs and cats often have inherited diseases common in random-bred populations. They can also inherit disease liability genes shared by the parent breeds or parent species. So if youre breeding short-statured breeds together, it wouldnt be surprising to see patellar luxation, or in smaller toy size breeds, to see mitral valve disease, he said.

Hereditary disease manifests as a result of anatomical mismatch between parent breeds. We see a lot of this in dental disease, where we see crowding of teeth and malocclusions and misplaced teeth, Dr. Bell continued. Even in the musculoskeletal, if you breed two breeds with different body types together, we may see degenerative joint disease and poor joints. All of these things, all need to be monitored.

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Making sense of genetic disease in dogs and cats - American Veterinary Medical Association

The revolution of genetic testing has led to more accurate and widespread assays for patients with cancer; however, as more genetic variants are identified, it has become a greater challenge to determine the optimal treatment for an individual patient, according to GouthamNarla, MD, PhD.

As we sequence more genes, we will have more information, which is a good thing, said Narla. Of course, we will also find more variants that, at this time, we don't know whether they're pathogenic or benign. They get lumped into the uncertain category, which creates uncertainty for patients and for providers, as well.

In an interview withOncLiveduring the 2020 Institutional Perspectives in Cancer (IPC) webinar on Precision Medicine, Narla, an associate professor in the Department of Medicine; chief of the Division of Genetic Medicine, Department of Medicine; and associate director of the Medical Scientist Training Program, University of Michigan, further discussed the utility of genomic testing and updates in next generation sequencing (NGS).

OncLive: Could you discuss the key advances in cancer genetics? What are some of the mechanisms that have driven its development?

Narla: A couple of major advancements we've seen in cancer genetics is the identification of additional disease-causing variants. It used to be when I first trained as a medical geneticist, we really only knew about BRCA1/2 and some of the mismatch repair genes. Now, we know about other genes, including PALB2, and other members and genes in that family. That has expanded the testing opportunities for our patients.

The other aspect that has been very exciting is now some of these gene variants are predictive of response to therapies. We have therapies that can be specifically used and work for patients who harbor some of these germline variants. That has really changed the way in which we have treated patients who carry these variants.

What are some of the recent developments in NGS?

Previously, we were doing single-gene testing, oftentimes by Sanger sequencing. Now, we can do large panels of genes depending upon the company and the panel; these comprise anywhere from 60 to 70 genesin some cases, several thousand genes. It has allowed us to collect vast amounts of sequencing information. Some of it will not be directly actionable now, but it still fuels research opportunities for us at major academic medical centers, and when more knowledge [is] gained, we go back to some of those sequencing results to see if, in fact, there was something that is now actionable based upon new knowledge.

How are we using this information to develop targeting strategies?

A lot of the approaches that we are using now may not involve the directly targeting the defective gene or protein, but they are leveraging knowledge about how that defective gene or protein causes activation of targetable pathways. For example, when it comes to BRCA1 loss, that creates a unique opportunity to use a PARP inhibitor in a synthetic lethal interaction, where those cells become highly dependent upon that enzyme. Then, you can inhibit with small molecules [or perhaps] approved PARP inhibitors, such as olaparib (Lynparza), and others for which there are now [a number of approved drugs that can target] a range of BRCA-deficient metastatic tumors.

How else has genomic testing evolved?

The evolution has been both in the number of individuals that we test, as well as how many genes we test. [For example, we used to] test families in which there are numbers of individuals who have cancer and we had a strong pretest probability that they would have a germline variant. Now, in fact, every patient with metastatic ovarian cancer, regardless of family history, gets tested. This is because we have PARP inhibitors for them. It not only has implications for their family but it also has implications for their treatment choices.

What guidelines have been helpful to your practice as it relates to genomic testing?

There are a number of organizations from the American Cancer Society to National Cancer Institute and the National Comprehensive Cancer Network (NCCN) that have very robust guidelines on who to test. There is also a little bit of subjectivity in making an appraisal with a genetics professional, meaning a genetic counselor or a medical geneticist, because not every family will fit the structure or will even know the entirety of their family history. There is some nuance to this, but there are definitely very established guidelines that exist and that we use when making these types of decisions.

However, the NCCN guidelines are very good and are used by [our institution. Then we apply our own nuances when we see the patient on a case by case basis. But, [in terms of] informing who should be tested and who should not, and which individual in the family should be [tested], the NCCN guidelines are a very good [resource].

What challenges could be addressed with future research?

I would like to see more of an effort to share data across all institutions and testing companies to reclassify these variants. I would like to see more basic science and translational science around what we call variant reclassification, so that we can really make definitive calls about the sequence changes that we see. The more genes we sequence, the more variants we find, and on larger panels, [we can see these uncertain variants in up to] 20% of patients. We're finding something in a gene, but we don't know whether it's good or bad for the patient.

Are there any new capabilities or technologies emerging that you find particularly exciting?

From a technology perspective, the last 10 years in sequencing has been a revolution; the cost of sequencing has come down and the accuracy has gone up. I'm not sure that we're going to see that much more of a revolution in the sequencing technology; it will be more efficient and more cost effective. We're [going to see] the identification of new genes associated with disease [and will therefore] it will be in the variant reclassification space.

What testing or sequencing studies are of particular interest?

One type of study that has read-out recently comprise the effectiveness of immunotherapy in patients who have mismatch repair deficient tumors. That has been really game-changing for those patients. The other major study is the use of PARP inhibitors in BRCA-mutant tumorsoriginally in the second- and third-line settings of ovarian cancer. [PARP inhibitors] have now moved to maintenance [therapy], pancreatic cancer, prostate cancer, and others. That has changed the management of patients with BRCA-positive tumors.

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Identifying Genetic Variants, Matching With Targeted Therapies Serve as Next Great Challenge With Germline Testing in Oncology - OncLive

TORONTO -- For the thousands of Canadians at risk of blindness, eight-year-old Sam is a beacon of hope.

He is the first Canadian to be treated with gene replacement therapy for a rare form of blindness which had left Sam unable to see sky on a cloudy day, and unable to make out shapes in the dark.

Sometimes you have to walk in the night and I couldnt see things and you bump into things, Sam told CTV News.

He had to have lights on always, and had trouble seeing his shoes or objects on the floor. And the condition was progressive, meaning things would get worse as he grew older -- a daunting prospect when there was no treatment available.

But now he can see cloudy skies, shoes and more. The best part of his improved vision, says Sam, are the stars at night.

I never saw stars before, he said. And I also never saw airplanes flying at night.

He was diagnosed after birth with a genetic disorder called retinitis pigmentosa, a form of genetic retinal degeneration resulting from mutations in the RPE65 gene.

You lose perception of light, Dr. Elise Heon, of Sick Kids Hospital, explained to CTV News. You end up in darkness and [its] slowly progressive, it's relentless, your visual field shrinks and shrinks and shrinks and shrinks.

Retinitis pigmentosa (RP) affects between 1 in 3,500 to 1 in 4,000 Canadians, according to Fighting Blindness Canada. It actually refers to a group of disorders, as there are numerous versions of RP depending on which pair of genes are damaged. More than 64 genes have been identified by scientists as potentially having mutations that cause RP.

Now, Canada has approved the first-ever gene replacement therapy for this form of blindness. Sick Kids Hospital has 29 children in its program with this mutation. The drug can be used on children and adults with the condition, but the earlier its used, the more sight it will save, doctors believe.

It's a huge deal, because for these patients before, theres no treatments, Heon said.

She said she had recently met two patients, brothers, who were suffering the same problem as Sam, and for the first time, she was able to provide hope.

They're 10 years old, and they're losing their vision, she said. If we do nothing, they're just going, fine, they'll just end up with no light reception. So for the first time [we were] able to say, well, actually we need to have a discussion. And it was just, it was priceless.

The gene therapy, which goes by the brand name Luxturna, was developed in the U.S by the drug company Spark Therapeutics.

It works by placing a copy of the healthy gene into inactivated viruses, which are then injected into the retina. The gene then allows cells to produce the necessary protein to convert light into an electrical signal in the retina in order to provide healthy vision and prevent progression of the disease.

It is the first targeted gene therapy to be approved by Health Canada, which gave it the all-clear this week.

Back in 2019, Sam and his family travelled to the U.S to get the new gene therapy because it wasnt available in Canada yet.

His mother, Sarah Banon, noticed changes quickly.

About a week later, I noticed he could get dressed by [himself], she said. He could get his shoes on by himself, independently.

His improvements have continued in the year since he first received the gene therapy.

He is so much more confident, his mother told CTV News. Like getting dressed by himself, matching clothes, doesnt have to have things enlarged. Being able to [see], even when its dark outside, no lights on and it is a cloudy day. He would have to, at school, keep the lights on.

Now he is able to function as a normal child.

With the approval of this gene therapy in Canada, doctors are hoping to be able to use it on more patients who qualify -- and the earlier the better.

Dr. Peter Kertes, a vitreo-retinal surgeon and Ophthalmologist-in-Chief at Sunnybrook Health Sciences Centre, told CTV News that the approval of the therapy is fantastic.

This is a huge breakthrough, he said. Most of the advances that we have in medicine are incremental. Every once in a while, once in a generation, something revolutionary like this comes along that really changes the course of therapy.

Luxturna specifically treats individuals with biallelic mutations of the RPE65 gene -- meaning they have mutations in that gene stemming from both parents -- which manifests as either RP or Leber congenital amaurosis (LCA). Its a very small patient group compared to the entirety of Canadians with inherited retinal diseases.

This may be just one gene therapy for one condition, but it will open to the door to this strategy being used in other scenarios, Kertes pointed out.

This is the tip of the iceberg. I think this is a vector that will prove to be very effective and holds great promise, he said. I think many people who are living with blindness or facing blindness, have much to look forward to. I think we're on the cusp of a revolution in this group of diseases.

The company licensing the therapy, Novartis Pharmaceuticals Canada Inc., isnt detailing the cost, but based on the price in the U.S it could top $1.1 million in Canada, making it among the most expensive drugs in the country.

The therapy is currently under review by both the Canadian Agency for Drugs and Technologies in Health (CADTH) and the Institut national dexcellence en sant et en services sociaux (INESSS).

Novartis said in a statement that they look forward to receiving their recommendations following Health Canadas approval.

They said they are eager to help eligible Canadians affected by this rare disease gain access to the first-ever gene replacement therapy as quickly as possible.

The Patented Medicine Prices Review Board will be disclosing their new guidelines in terms of capping drug prices in an online media briefing this Thursday.

As this will likely be the first of many gene replacement therapies -- with similarly high price tags -- Ottawa and the provinces will have to make the decision on whether it will be covered by provincial health plans. The question is an ongoing ethical debate, with some saying that drug companies will only take advantage of it if governments show that they are willing to pay.

Should it be the responsibility for the government to pay for any drug at any price? Marc-Andr Gagnon, a researcher with Carleton University who looks into pharmaceutical policy, told CTV News. The problem is, if we say yes to this question, you can be sure that the day after, all the drugs in the market will be asking for much higher prices.

Its a very expensive drug, Heon acknowledged.

However, she pointed out that this is a rare disease, and its not a recurrent treatment. Its a one-time injection to the eyes.

You treat both eyes and then thats it, she said.

To be able to change someone's life is quite a privilege. And to be able to prevent someone from going blind is a real privilege.

For Sam and his mother, the gift of independence has been priceless.

This is a story of hope, his mother said. A child told it is what it is.

And now, when he looks up at night, he can see stars.

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'I never saw stars before': Gene therapy brings back 8-year-old Canadian boy's sight - CTV News