Longevity Conferences 2023
January 19, 2023
Curated list of Longevity Conferences, where you can explore the latest research and developments in the field of aging and longevity.
All Articles
Restoring vision with gene therapy: Shedding the light on LUMEVOQ®
LUMEVOQ® or (GS010) is a gene therapy that has been tested as a treatment for Leber hereditary optic neuropathy (LHON).
Highlights:
- Leber hereditary optic neuropathy (LHON) is a genetic condition that affects the optic nerve and arises from mitochondrial dysfunction
- Males in their 20s and 30s are more liable to develop the condition
- There are several genes associated with the conditions
- The 11778G>A mutation is the most prevalent, constituting 70% of cases
- LUMEVOQ® gene therapy has been tested and proved to be effective in tackling this condition
Introduction
Leber hereditary optic neuropathy (LHON) is a maternally inherited condition characterized by rapid, severe, and progressive bilateral vision loss due to optic nerve damage. This condition arises from point mutations that affect mitochondrial DNA, disrupting the organelle’s function. The retinal ganglion cells are most affected by these mutations because these cells are highly susceptible to disrupted adenosine triphosphate (ATP) production and oxidative stress. The onset of LHON peaks around the second and third decades of life, leading to loss of vision before the age of 50 years in 90% of cases.
Understanding the disease
The first description of LHON dates back to 1871 when a German ophthalmologist named Theodore Leber described the clinical features of the disease (1). This condition was the first disorder attributed to mutations in the mitochondrial DNA (mtDNA) (2). Literature highlights that this condition affects males four to five times more likely than females; however, sex does not influence the severity of the disease (1).
LHON is a multifactorial condition where lifestyle and environmental factors play a role. A study by Kirkman et al. involving 196 affected individuals and 206 carriers highlighted that smoking was strongly associated with vision loss (3). The latter outcome was independent of alcohol consumption status or gender. Additionally, the study found that alcohol also contributes to vision loss; however, a strong correlation was found with heavy consumption only. The contribution of smoking to this condition is manifested in the fact that it compromises the activity of complex I (an enzyme involved in oxidative phosphorylation reactions that lead to energy production), reduces cytochrome c oxidase activity (an enzyme that regulates oxygen consumption by the mitochondria), and increases the production of reactive oxygen species (ROS) (2). Factors like the use of antiretroviral medications and antibiotics, like zidovudine, ethambutol, and aminoglycosides, have also been highlighted as triggers for LOHN. This is because these agents are known to interfere with mitochondrial respiratory function (4).
As mentioned earlier, LHON is a disease of genetic origin. According to research, the 11778G>A/ND4 mtDNA mutation in the MT-ND4 (MT-ND4 is a gene that codes NADH dehydrogenase, which is a part of complex I) is the most prevalent, accounting for 70% of cases worldwide (5, 6). Other dominant mutations include the m.14484T>C mutation in the MT-ND6 gene and the m.3460G>A in the MT-ND1 gene. These mutations affect various targets and pathways like complex I, leading to degeneration and activation of apoptosis in the retinal ganglion cells.
Estimates reveal that the incidence of LHON is between 1:31,000 and 1:54,000 (5). As mentioned earlier, LHON is more prevalent in young adults; however, there have been reports highlighting that people aged 2 to 87 years have been affected by the disease.
Literature mentions that visual recovery is affected by the type of mitochondrial mutation, with the majority of the individuals affected by LHON remaining significantly visually impaired for life (7). Less harmful forms of the mutations, like the m.14484T>C mutation, have a recovery rate of up to 60%, while more deleterious ones like the m.11778G>A mutation only have less than 20% chance to have some visual recovery.
LHON treatment modalities
Different treatment modalities have been suggested to tackle the condition. These management strategies are incorporated in various phases of the disease, before, during, or after vision loss (8).
The use of antioxidants to address LHON has been suggested. The goal of this approach is to improve mitochondrial respiration and reduce the deleterious effects of ROS (8). To validate this approach, various interventions with antioxidant capacity have been suggested; examples include vitamins like B2, E, and B2 and supplements like glutathione (9, 10). Data supporting these interventions have been evaluated in a systematic review by Pferffer et al. The results of their study highlighted insufficient evidence to reach a definitive conclusion regarding these interventions in mitochondrial disorders (10). Stem cell therapy has also been suggested as a treatment modality; however, there is insufficient clinical data to draw a conclusion that supports its use (8).
Another suggested approach to tackle LHON is mitochondrial replacement therapy, also known as mitochondrial donation. The concept of this approach depends on preventing transmission of the pathogenic mtDNA from mother to fetus by replacing the said defective genetic material (11). In this technique, parental nuclear material is transferred into a mitochondrial donor zygote that carries a normal mtDNA (11, 12). This way, when pregnancy concludes, and the fetus is delivered, the child’s genetic material will be from the biological parents, while the mitochondrial genome will be from the donor. This technique carries a number of risks, such as mismatch between mitochondrial and nuclear genome in addition to ethical considerations (12). Nevertheless, there is a documented case of utilization of such technique in a procedure that took place in Mexico in 2016. The outcome of the said case yielded the birth of a healthy young male who had an mtDNA mutation load of 2.36-9.23% (13). To understand the value of the latter outcome, literature has highlighted that a mutational load of 60-70% is required to display severe symptoms.
Gene therapy has also been explored as a treatment modality. This is because the effectiveness of using viral vectors to deliver gene therapy has shown promising results (12). Before utilizing this approach, it is important to understand some of the challenges that come with it. For example, a higher amount of the gene is required to be delivered to achieve a tangible effect upon its expression (8). In the case of LHON, it is even more challenging because the mitochondria possess a double membrane structure that makes it more difficult to deliver the treatment, mainly due to the low permeability of the inner layer (14). To overcome this physical barrier, an approach called allotopic expression has been leveraged (12). In this process, deliberate translocation of mitochondrial genes occurs through a polypeptide imported from the cytoplasm (15). In other words, it is the functional relocation of mitochondrial genes into the nucleus, followed by the import of the gene-encoded protein into the mitochondria (8). To achieve this delivery, the gene is required to be loaded on an adenovirus-associated vector (AAV) and the encoded protein tagged with a mitochondrial targeting sequence (MTS) to allow its import into the mitochondrial department (12, 15).
Experience with LUMEVOQ®
LUMEVOQ® or (GS010) is a gene therapy that has been tested as a treatment for LHON. The medication is a recombinant adenovirus vector that is loaded with a wild-type mitochondrial ND4 and an MTS to achieve mitochondrial translocation (16). It has been developed by GenSight Biologics, a company that specializes in developing innovative gene therapies for neurodegenerative disorders and central nervous system diseases (17). In the preclinical stages, the therapeutic agent restored complex I activity and ATP synthesis in defective mitochondria. These promising results prompted the initiation of human studies, where primary studies of this genetic therapy on humans deemed it safe and well-tolerated (18, 19). The RESCUE and REVERSE were phase III pivotal trials that demonstrated the efficacy and safety of this treatment in patients suffering from LHON (16, 17, 20).
The efficacy of this agent has been tested on human subjects carrying the m.11778G>A mutation and suffering from bilateral vision loss within the 6 to 12 months prior to the study (16). The trial subjects received the therapeutic agent in one eye and a placebo in the other, and efficacy was evaluated based on measuring best-corrected visual acuity (BCVA) using the early treatment of diabetic retinopathy study (ETDRS) chart, among other tests. BCVA test and the ETDRS chart tell how good a vision is by the capacity to read letters. Results of the study highlighted that the eyes treated with the gs010 showed an improvement in BCVA results translated in the form of +15 ETDRS letters compared to +13 in placebo. The results indicated that the primary endpoint was not met. To better understand the results obtained with placebo, the investigators suggested that this improvement is attributed to the transfer of the viral vector from the treated eye to the other (16). These results were later consolidated by outcomes from other studies, including a systematic review that indicated that statistically significant and clinically relevant outcomes were maintained for over four years of follow-up (20,21). Currently, the review of the European Marketing Authorization Application for LUMEVOQ® is ongoing, with the decision from the Committee for Medicinal Products for Human Use expected in the fourth quarter of 2022 (17).
Conclusions
LHON is a hereditary condition that is predominant primarily in males. In most instances, this condition affects people at a young age, causing a significant reduction in life quality. Many treatment modalities have been suggested, but the efficacy of some is questionable. Genetic therapy has been investigated and demonstrated effectiveness in several clinical settings. In addition to treatment, genetic counseling provides a great value, as parents would be able to understand the risks associated with the disease and how their offspring might be affected by the condition. Individuals living with LHON should be recommended to quit tobacco smoking, avoid exposure to smoke, minimize or avoid alcohol use, and implement a healthy diet. Additionally, people should also be warned against scamming activities that suggest the use of stem cells to promote optic nerve regeneration, as there is insufficient clinical evidence to support this approach.
References
1. Yu-Wai-Man P, Chinnery PF. Leber Hereditary Optic Neuropathy - Therapeutic Challenges and Early Promise. Taiwan journal of ophthalmology. 2011;1(1):12-5.
2. Meyerson C, Van Stavern G, McClelland C. Leber hereditary optic neuropathy: current perspectives. Clinical ophthalmology (Auckland, NZ). 2015;9:1165-76.
3. Kirkman MA, Yu-Wai-Man P, Korsten A, Leonhardt M, Dimitriadis K, De Coo IF, et al. Gene-environment interactions in Leber hereditary optic neuropathy. Brain : a journal of neurology. 2009;132(Pt 9):2317-26.
4. Sadun AA, La Morgia C, Carelli V. Leber's Hereditary Optic Neuropathy. Curr Treat Options Neurol. 2011;13(1):109-17.
5. Theodorou-Kanakari A, Karampitianis S, Karageorgou V, Kampourelli E, Kapasakis E, Theodossiadis P, et al. Current and Emerging Treatment Modalities for Leber's Hereditary Optic Neuropathy: A Review of the Literature. Advances in therapy. 2018;35(10):1510-8.
6. Catarino CB, Ahting U, Gusic M, Iuso A, Repp B, Peters K, et al. Characterization of a Leber's hereditary optic neuropathy (LHON) family harboring two primary LHON mutations m.11778G>A and m.14484T>C of the mitochondrial DNA. Mitochondrion. 2017;36:15-20.
7. Jurkute N, Yu-Wai-Man P. Leber hereditary optic neuropathy: bridging the translational gap. Current opinion in ophthalmology. 2017;28(5):403-9.
8. Hage R, Vignal-Clermont C. Leber Hereditary Optic Neuropathy: Review of Treatment and Management. Frontiers in Neurology. 2021;12.
9. Newman NJ. Treatment of Leber hereditary optic neuropathy. Brain : a journal of neurology. 2011;134(Pt 9):2447-50.
10. Pfeffer G, Majamaa K, Turnbull DM, Thorburn D, Chinnery PF. Treatment for mitochondrial disorders. Cochrane Database of Systematic Reviews. 2012(4).
11. Kang E, Wu J, Gutierrez NM, Koski A, Tippner-Hedges R, Agaronyan K, et al. Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Nature. 2016;540(7632):270-5.
12. Kim US, Jurkute N, Yu-Wai-Man P. Leber Hereditary Optic Neuropathy—Light at the End of the Tunnel? The Asia-Pacific Journal of Ophthalmology. 2018;7(4).
13. Zhang J, Liu H, Luo S, Lu Z, Chávez-Badiola A, Liu Z, et al. Live birth derived from oocyte spindle transfer to prevent mitochondrial disease. Reprod Biomed Online. 2017;34(4):361-8.
14. Yu-Wai-Man P. Genetic manipulation for inherited neurodegenerative diseases: myth or reality? The British journal of ophthalmology. 2016;100(10):1322-31.
15. Artika IM. Allotopic expression of mitochondrial genes: Basic strategy and progress. Genes & Diseases. 2020;7(4):578-84.
16. Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Sadun AA, et al. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Sci Transl Med. 2020;12(573).
17. Center AE. GenSight Biologics reports clinically meaningful vision improvement is maintained 4 years after one-time treatment with LUMEVOQ® gene therapy.
18. Vignal C, Uretsky S, Fitoussi S, Galy A, Blouin L, Girmens J-F, et al. Safety of rAAV2/2-<em>ND4</em> Gene Therapy for Leber Hereditary Optic Neuropathy. Ophthalmology. 2018;125(6):945-7.
19. Bouquet C, Vignal Clermont C, Galy A, Fitoussi S, Blouin L, Munk MR, et al. Immune Response and Intraocular Inflammation in Patients With Leber Hereditary Optic Neuropathy Treated With Intravitreal Injection of Recombinant Adeno-Associated Virus 2 Carrying the ND4 Gene: A Secondary Analysis of a Phase 1/2 Clinical Trial. JAMA Ophthalmol. 2019;137(4):399-406.
20. Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, et al. Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset. Ophthalmology. 2021;128(5):649-60.
21. Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, et al. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Frontiers in neurology. 2021;12:662838-.
Read this article now
Sign up to get immediate access to this article and professional education in longevity medicine.
Oops! Something went wrong while submitting the form.
OUR partnering associations
Highlights:
- Leber hereditary optic neuropathy (LHON) is a genetic condition that affects the optic nerve and arises from mitochondrial dysfunction
- Males in their 20s and 30s are more liable to develop the condition
- There are several genes associated with the conditions
- The 11778G>A mutation is the most prevalent, constituting 70% of cases
- LUMEVOQ® gene therapy has been tested and proved to be effective in tackling this condition
Introduction
Leber hereditary optic neuropathy (LHON) is a maternally inherited condition characterized by rapid, severe, and progressive bilateral vision loss due to optic nerve damage. This condition arises from point mutations that affect mitochondrial DNA, disrupting the organelle’s function. The retinal ganglion cells are most affected by these mutations because these cells are highly susceptible to disrupted adenosine triphosphate (ATP) production and oxidative stress. The onset of LHON peaks around the second and third decades of life, leading to loss of vision before the age of 50 years in 90% of cases.
Understanding the disease
The first description of LHON dates back to 1871 when a German ophthalmologist named Theodore Leber described the clinical features of the disease (1). This condition was the first disorder attributed to mutations in the mitochondrial DNA (mtDNA) (2). Literature highlights that this condition affects males four to five times more likely than females; however, sex does not influence the severity of the disease (1).
LHON is a multifactorial condition where lifestyle and environmental factors play a role. A study by Kirkman et al. involving 196 affected individuals and 206 carriers highlighted that smoking was strongly associated with vision loss (3). The latter outcome was independent of alcohol consumption status or gender. Additionally, the study found that alcohol also contributes to vision loss; however, a strong correlation was found with heavy consumption only. The contribution of smoking to this condition is manifested in the fact that it compromises the activity of complex I (an enzyme involved in oxidative phosphorylation reactions that lead to energy production), reduces cytochrome c oxidase activity (an enzyme that regulates oxygen consumption by the mitochondria), and increases the production of reactive oxygen species (ROS) (2). Factors like the use of antiretroviral medications and antibiotics, like zidovudine, ethambutol, and aminoglycosides, have also been highlighted as triggers for LOHN. This is because these agents are known to interfere with mitochondrial respiratory function (4).
As mentioned earlier, LHON is a disease of genetic origin. According to research, the 11778G>A/ND4 mtDNA mutation in the MT-ND4 (MT-ND4 is a gene that codes NADH dehydrogenase, which is a part of complex I) is the most prevalent, accounting for 70% of cases worldwide (5, 6). Other dominant mutations include the m.14484T>C mutation in the MT-ND6 gene and the m.3460G>A in the MT-ND1 gene. These mutations affect various targets and pathways like complex I, leading to degeneration and activation of apoptosis in the retinal ganglion cells.
Estimates reveal that the incidence of LHON is between 1:31,000 and 1:54,000 (5). As mentioned earlier, LHON is more prevalent in young adults; however, there have been reports highlighting that people aged 2 to 87 years have been affected by the disease.
Literature mentions that visual recovery is affected by the type of mitochondrial mutation, with the majority of the individuals affected by LHON remaining significantly visually impaired for life (7). Less harmful forms of the mutations, like the m.14484T>C mutation, have a recovery rate of up to 60%, while more deleterious ones like the m.11778G>A mutation only have less than 20% chance to have some visual recovery.
LHON treatment modalities
Different treatment modalities have been suggested to tackle the condition. These management strategies are incorporated in various phases of the disease, before, during, or after vision loss (8).
The use of antioxidants to address LHON has been suggested. The goal of this approach is to improve mitochondrial respiration and reduce the deleterious effects of ROS (8). To validate this approach, various interventions with antioxidant capacity have been suggested; examples include vitamins like B2, E, and B2 and supplements like glutathione (9, 10). Data supporting these interventions have been evaluated in a systematic review by Pferffer et al. The results of their study highlighted insufficient evidence to reach a definitive conclusion regarding these interventions in mitochondrial disorders (10). Stem cell therapy has also been suggested as a treatment modality; however, there is insufficient clinical data to draw a conclusion that supports its use (8).
Another suggested approach to tackle LHON is mitochondrial replacement therapy, also known as mitochondrial donation. The concept of this approach depends on preventing transmission of the pathogenic mtDNA from mother to fetus by replacing the said defective genetic material (11). In this technique, parental nuclear material is transferred into a mitochondrial donor zygote that carries a normal mtDNA (11, 12). This way, when pregnancy concludes, and the fetus is delivered, the child’s genetic material will be from the biological parents, while the mitochondrial genome will be from the donor. This technique carries a number of risks, such as mismatch between mitochondrial and nuclear genome in addition to ethical considerations (12). Nevertheless, there is a documented case of utilization of such technique in a procedure that took place in Mexico in 2016. The outcome of the said case yielded the birth of a healthy young male who had an mtDNA mutation load of 2.36-9.23% (13). To understand the value of the latter outcome, literature has highlighted that a mutational load of 60-70% is required to display severe symptoms.
Gene therapy has also been explored as a treatment modality. This is because the effectiveness of using viral vectors to deliver gene therapy has shown promising results (12). Before utilizing this approach, it is important to understand some of the challenges that come with it. For example, a higher amount of the gene is required to be delivered to achieve a tangible effect upon its expression (8). In the case of LHON, it is even more challenging because the mitochondria possess a double membrane structure that makes it more difficult to deliver the treatment, mainly due to the low permeability of the inner layer (14). To overcome this physical barrier, an approach called allotopic expression has been leveraged (12). In this process, deliberate translocation of mitochondrial genes occurs through a polypeptide imported from the cytoplasm (15). In other words, it is the functional relocation of mitochondrial genes into the nucleus, followed by the import of the gene-encoded protein into the mitochondria (8). To achieve this delivery, the gene is required to be loaded on an adenovirus-associated vector (AAV) and the encoded protein tagged with a mitochondrial targeting sequence (MTS) to allow its import into the mitochondrial department (12, 15).
Experience with LUMEVOQ®
LUMEVOQ® or (GS010) is a gene therapy that has been tested as a treatment for LHON. The medication is a recombinant adenovirus vector that is loaded with a wild-type mitochondrial ND4 and an MTS to achieve mitochondrial translocation (16). It has been developed by GenSight Biologics, a company that specializes in developing innovative gene therapies for neurodegenerative disorders and central nervous system diseases (17). In the preclinical stages, the therapeutic agent restored complex I activity and ATP synthesis in defective mitochondria. These promising results prompted the initiation of human studies, where primary studies of this genetic therapy on humans deemed it safe and well-tolerated (18, 19). The RESCUE and REVERSE were phase III pivotal trials that demonstrated the efficacy and safety of this treatment in patients suffering from LHON (16, 17, 20).
The efficacy of this agent has been tested on human subjects carrying the m.11778G>A mutation and suffering from bilateral vision loss within the 6 to 12 months prior to the study (16). The trial subjects received the therapeutic agent in one eye and a placebo in the other, and efficacy was evaluated based on measuring best-corrected visual acuity (BCVA) using the early treatment of diabetic retinopathy study (ETDRS) chart, among other tests. BCVA test and the ETDRS chart tell how good a vision is by the capacity to read letters. Results of the study highlighted that the eyes treated with the gs010 showed an improvement in BCVA results translated in the form of +15 ETDRS letters compared to +13 in placebo. The results indicated that the primary endpoint was not met. To better understand the results obtained with placebo, the investigators suggested that this improvement is attributed to the transfer of the viral vector from the treated eye to the other (16). These results were later consolidated by outcomes from other studies, including a systematic review that indicated that statistically significant and clinically relevant outcomes were maintained for over four years of follow-up (20,21). Currently, the review of the European Marketing Authorization Application for LUMEVOQ® is ongoing, with the decision from the Committee for Medicinal Products for Human Use expected in the fourth quarter of 2022 (17).
Conclusions
LHON is a hereditary condition that is predominant primarily in males. In most instances, this condition affects people at a young age, causing a significant reduction in life quality. Many treatment modalities have been suggested, but the efficacy of some is questionable. Genetic therapy has been investigated and demonstrated effectiveness in several clinical settings. In addition to treatment, genetic counseling provides a great value, as parents would be able to understand the risks associated with the disease and how their offspring might be affected by the condition. Individuals living with LHON should be recommended to quit tobacco smoking, avoid exposure to smoke, minimize or avoid alcohol use, and implement a healthy diet. Additionally, people should also be warned against scamming activities that suggest the use of stem cells to promote optic nerve regeneration, as there is insufficient clinical evidence to support this approach.
References
1. Yu-Wai-Man P, Chinnery PF. Leber Hereditary Optic Neuropathy - Therapeutic Challenges and Early Promise. Taiwan journal of ophthalmology. 2011;1(1):12-5.
2. Meyerson C, Van Stavern G, McClelland C. Leber hereditary optic neuropathy: current perspectives. Clinical ophthalmology (Auckland, NZ). 2015;9:1165-76.
3. Kirkman MA, Yu-Wai-Man P, Korsten A, Leonhardt M, Dimitriadis K, De Coo IF, et al. Gene-environment interactions in Leber hereditary optic neuropathy. Brain : a journal of neurology. 2009;132(Pt 9):2317-26.
4. Sadun AA, La Morgia C, Carelli V. Leber's Hereditary Optic Neuropathy. Curr Treat Options Neurol. 2011;13(1):109-17.
5. Theodorou-Kanakari A, Karampitianis S, Karageorgou V, Kampourelli E, Kapasakis E, Theodossiadis P, et al. Current and Emerging Treatment Modalities for Leber's Hereditary Optic Neuropathy: A Review of the Literature. Advances in therapy. 2018;35(10):1510-8.
6. Catarino CB, Ahting U, Gusic M, Iuso A, Repp B, Peters K, et al. Characterization of a Leber's hereditary optic neuropathy (LHON) family harboring two primary LHON mutations m.11778G>A and m.14484T>C of the mitochondrial DNA. Mitochondrion. 2017;36:15-20.
7. Jurkute N, Yu-Wai-Man P. Leber hereditary optic neuropathy: bridging the translational gap. Current opinion in ophthalmology. 2017;28(5):403-9.
8. Hage R, Vignal-Clermont C. Leber Hereditary Optic Neuropathy: Review of Treatment and Management. Frontiers in Neurology. 2021;12.
9. Newman NJ. Treatment of Leber hereditary optic neuropathy. Brain : a journal of neurology. 2011;134(Pt 9):2447-50.
10. Pfeffer G, Majamaa K, Turnbull DM, Thorburn D, Chinnery PF. Treatment for mitochondrial disorders. Cochrane Database of Systematic Reviews. 2012(4).
11. Kang E, Wu J, Gutierrez NM, Koski A, Tippner-Hedges R, Agaronyan K, et al. Mitochondrial replacement in human oocytes carrying pathogenic mitochondrial DNA mutations. Nature. 2016;540(7632):270-5.
12. Kim US, Jurkute N, Yu-Wai-Man P. Leber Hereditary Optic Neuropathy—Light at the End of the Tunnel? The Asia-Pacific Journal of Ophthalmology. 2018;7(4).
13. Zhang J, Liu H, Luo S, Lu Z, Chávez-Badiola A, Liu Z, et al. Live birth derived from oocyte spindle transfer to prevent mitochondrial disease. Reprod Biomed Online. 2017;34(4):361-8.
14. Yu-Wai-Man P. Genetic manipulation for inherited neurodegenerative diseases: myth or reality? The British journal of ophthalmology. 2016;100(10):1322-31.
15. Artika IM. Allotopic expression of mitochondrial genes: Basic strategy and progress. Genes & Diseases. 2020;7(4):578-84.
16. Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Sadun AA, et al. Bilateral visual improvement with unilateral gene therapy injection for Leber hereditary optic neuropathy. Sci Transl Med. 2020;12(573).
17. Center AE. GenSight Biologics reports clinically meaningful vision improvement is maintained 4 years after one-time treatment with LUMEVOQ® gene therapy.
18. Vignal C, Uretsky S, Fitoussi S, Galy A, Blouin L, Girmens J-F, et al. Safety of rAAV2/2-<em>ND4</em> Gene Therapy for Leber Hereditary Optic Neuropathy. Ophthalmology. 2018;125(6):945-7.
19. Bouquet C, Vignal Clermont C, Galy A, Fitoussi S, Blouin L, Munk MR, et al. Immune Response and Intraocular Inflammation in Patients With Leber Hereditary Optic Neuropathy Treated With Intravitreal Injection of Recombinant Adeno-Associated Virus 2 Carrying the ND4 Gene: A Secondary Analysis of a Phase 1/2 Clinical Trial. JAMA Ophthalmol. 2019;137(4):399-406.
20. Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, et al. Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset. Ophthalmology. 2021;128(5):649-60.
21. Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, et al. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Frontiers in neurology. 2021;12:662838-.
Article reviewed by
Close
Dr. Ana Baroni MD. Ph.D.
Scientific & Medical Advisor
Quality Garant
Ana has over 20 years of consultancy experience in longevity, regenerative and precision medicine. She has a multifaceted understanding of genomics, molecular biology, clinical biochemistry, nutrition, aging markers, hormones and physical training. This background allows her to bridge the gap between longevity basic sciences and evidence-based real interventions, putting them into the clinic, to enhance the healthy aging of people. She is co-founder of Origen.life, and Longevityzone. Board member at Breath of Health, BioOx and American Board of Clinical Nutrition. She is Director of International Medical Education of the American College of Integrative Medicine, Professor in IL3 Master of Longevity at Barcelona University and Professor of Nutrigenomics in Nutrition Grade in UNIR University.
DISCOVER
HealthyLongevity.guide
Professional science-based education
250+ Articles, video lectures, webinars
Community of 1000+ verified professionals
.jpg)
