- Gene Therapy for Sickle Cell Disease
- Volunteerism and Disability Inclusion
Less than a month after receiving approval from the UK drug regulator for Casgevy, a gene therapy designed to treat individuals aged 12 and above with sickle cell disease and beta thalassemia, the U.S. FDA has now granted approval for two gene therapies—Casgevy and Lyfgenia—to address sickle cell disease in patients over the age of 12.
GS3- Science and Technology
- Developments and their Applications and Effects in Everyday Life
- Awareness in the field of Biotechnology
In the context of recent national and global efforts to treat Sickle Cell Disease, explain the causes and symptoms of the disease. Also, highlight the current developments in its treatment and their efficacy. (15 Marks, 250 Words)
Background: About Sickle Cell Disease:
- Sickle cell disease (SCD), also known as sickle cell anemia, is a genetic blood disorder that significantly impacts the affected individual’s entire life.
- It belongs to a group of inherited red blood cell disorders that affect hemoglobin, the protein responsible for carrying oxygen throughout the body.
- In normal circumstances, red blood cells exhibit a disc-shaped and flexible structure, allowing easy movement through blood vessels. However, in individuals with sickle cell disease, their red blood cells take on a crescent or “sickle”-shaped form.
- These abnormal cells lack flexibility and can obstruct blood flow, leading to severe complications such as stroke, eye issues, infections, and episodes of intense pain known as pain crises.
- SCD is an autosomal recessive condition, requiring two copies of the gene for the disease to manifest, while individuals with only one copy have sickle cell trait.
- Symptoms of sickle cell anemia typically manifest at a young age, with onset occurring around six months, though they may appear as early as four months in babies.
- The symptoms, which vary in severity across different types of SCD, include fatigue, irritability, fussiness in babies, bedwetting, jaundice (yellowing of the eyes and skin), swelling and pain in hands and feet, frequent infections, and chest, back, arm, or leg pain.
- Various government initiatives aim to address SCD, including the release of technical operational guidelines in 2016, the establishment of integrated centers for treatment and diagnosis in tribal districts, and the creation of the State Haemoglobinopathy Mission in Madhya Pradesh.
- The National Health Mission, supported by the Government of India, assists states in preventing and managing sickle cell disease.
- In the Union Budget 2023-24, the government announced a mission to eliminate Sickle cell Anaemia by 2047.
Working of the Recent Gene Therapies:
- These significant approvals signal the commencement of gene therapy utilizing the CRISPR-Cas9 tool to address diseases that traditionally could only be cured through bone marrow transplantation.
- CRISPR is a gene-editing technology that mimics the natural defense mechanism in bacteria. It involves the use of a special protein called Cas9 to cut and replace a specific DNA sequence responsible for the disease. The technology is often likened to “genetic scissors” and offers a programmable and efficient way to address genetic disorders, although the potential for errors exists.
- While Lyfgenia utilizes a disabled lentivirus as a vector to introduce a new gene for hemoglobin mimicking the healthy version into blood stem cells, Casgevy employs the gene-editing capabilities of CRISPR-Cas9 to disable a specific gene (BCL11A) responsible for inhibiting fetal hemoglobin production in blood stem cells.
- Approximately 10% of adults naturally continue to produce fetal hemoglobin, while in others, the BCL11A gene hinders fetal hemoglobin production.
- Disabling the BCL11A gene allows the production of fetal hemoglobin, which lacks the abnormalities of adult hemoglobin, providing effective treatment for patients with sickle cell disease or beta thalassemia.
Analysing the Efficacy of the Therapies:
- Clinical trials for Casgevy demonstrated that 28 out of 29 sickle cell disease patients receiving the gene therapy experienced relief from the debilitating effects of the disease for one year.
- In the case of beta thalassemia, 39 out of 42 patients did not require blood transfusions for one year, and in the remaining three, the need for blood transfusion was reduced by over 70%.
- Clinical trials involving Lyfgenia revealed that 30 out of 32 sickle cell disease patients did not suffer from severe blocked blood flow caused by sickle cells, while 28 out of 32 patients did not experience any blocked blood flow events six to 18 months post-infusion.
- As both gene therapies involve the use of patients’ own blood cells for gene editing, the potential treatment scope is substantial, eliminating the need for matching bone marrow donors.
- In practice, these treatments are likely to be prohibitively expensive. Similar to bone marrow transplantation, only specific hospitals will have the capability to extract a patient’s blood stem cells, apply the genetic editing tool to these cells, and subsequently reintroduce them. Consequently, the number of beneficiaries is constrained.
- Given that clinical trials have assessed the therapies in a relatively small number of patients for a limited duration, the imperative of continuously monitoring their safety and effectiveness through real-world data cannot be overstated.
The utilization of the CRISPR–Cas9 tool introduces the genuine risk of unintended genetic modifications and the associated side effects. Therefore, careful scrutiny and ongoing assessment are crucial in navigating potential risks and ensuring the therapies’ long-term safety and efficacy.
On December 3rd, the world observes the ‘International Day of Persons with Disabilities,’ recognizing the unique challenges faced by those with disabilities and advocating for their rights and well-being. Following closely on December 5th, ‘International Volunteers Day’ pays tribute to global volunteers who selflessly contribute their time and effort to make a positive impact in their communities.
GS2- Social Justice
- Welfare Schemes for Vulnerable Sections of the population by the Centre and States and the Performance of these Schemes;
- Mechanisms, Laws, Institutions and Bodies constituted for the Protection and Betterment of these Vulnerable Sections.
The advocacy of activists has made a dent in societal attitude towards people with disabilities but still a lot needs to be done. Discuss. (10 Marks, 150 Words).
Background: About Disability:
Disability arises from the interplay between individuals with impairments and the hindrances posed by attitudinal and environmental barriers, limiting their complete and effective engagement in society on an equal footing with others.
According to the World Health Organization (WHO):
- Approximately 1.3 billion people encounter significant disabilities, constituting 16% of the global population or 1 in 6 individuals.
- Some individuals with disabilities experience a lifespan up to 20 years shorter than those without disabilities.
- Persons with disabilities have a twofold increased risk of developing conditions such as depression, asthma, diabetes, stroke, obesity, or poor oral health.
- Persons with disabilities confront numerous health disparities.
- Accessing transportation is 15 times more challenging for persons with disabilities due to issues of inaccessibility and unaffordability compared to those without disabilities.
- Health inequities result from unjust conditions faced by persons with disabilities, encompassing stigma, discrimination, poverty, exclusion from education and employment, and obstacles encountered within the health system itself.
International Day of Disabled Persons (IDPD):
- In 1992, the United Nations General Assembly declared the International Day of Disabled Persons (IDPD) through resolution 47/3.
- This day aims to raise awareness of disability issues, advocate for the rights of individuals with disabilities, and ensure dignity for the differently-abled.
- The theme for this year’s IDPD is “United in action to rescue and achieve the SDGs for, with, and by persons with disabilities,” focusing on deepening understanding, gaining support for their rights and dignity, and highlighting the benefits of their inclusion in all aspects of life.
International Volunteers Day (IVD):
- Similarly, International Volunteers Day (IVD) on December 5th annually acknowledges the invaluable contributions of volunteers worldwide.
- Established by the UN General Assembly in 1985, IVD honors those who dedicate their time and skills to address societal challenges and make a difference in the lives of others.
- With over a billion volunteers globally, the day emphasizes the transformative impact of collective efforts on social, economic, and environmental progress.
2016 Rights of Persons with Disabilities Act:
- India, driven by the 2016 Rights of Persons with Disabilities Act championed by activist Javed Abidi, has made significant progress in acknowledging and promoting inclusivity.
- The Rights of Persons with Disabilities Act 2016 defines disability within an evolving and dynamic context.
- It broadens the categories of disabilities from 7 to 21, encompassing mental illness, autism spectrum disorder, cerebral palsy, muscular dystrophy, chronic neurological conditions, speech and language disability, thalassemia, hemophilia, sickle cell disease, multiple disabilities (including deaf blindness), acid attack victims, and Parkinson’s disease—categories that were previously overlooked. Moreover, the government has the authority to designate any other specified disability category.
- The Act enhances the reservation quota for individuals with disabilities from 3% to 4% in government jobs and from 3% to 5% in higher education institutions.
- Every child aged between 6 and 18 years with a benchmark disability is entitled to free education, and government-funded as well as recognized educational institutions must offer inclusive education.
- Special emphasis is placed on ensuring accessibility in public buildings within a stipulated timeframe, aligning with the objectives of the Accessible India Campaign.
- The Chief Commissioner for Persons with Disabilities and State Commissioners serve as regulatory bodies and Grievance Redressal agencies, overseeing the Act’s implementation.
- To provide financial assistance to individuals with disabilities, separate National and State Funds are established.
- Despite advancements, challenges persist, including attitudinal barriers and inadequate infrastructure.
- A survey conducted by the Disability Rights India Foundation (DRIF) in 2018 assessing the enforcement of the Rights of Persons with Disabilities (RPWD) Act in 24 States indicates that over 50% of them have not yet officially adopted the State rules.
- Among the states that have notified the rules are Bihar, Chandigarh, Manipur, Meghalaya, Odisha, Telangana, Tamil Nadu, and West Bengal, with only ten states having done so.
- Leveraging a robust tradition of volunteerism, ranging from grassroots initiatives to established NGOs, India harnesses the transformative potential of volunteers to break stereotypes, provide support, and foster inclusivity.
‘Accessible India’ campaign:
- The ‘Accessible India’ campaign initiated by the Government of India aims to enhance accessibility in public spaces, transportation, and information for persons with disabilities.
- It serves as the flagship nationwide initiative of the Department of Empowerment of Persons with Disabilities (DEPwD), operating under the Ministry of Social Justice and Empowerment.
- Launched on the International Day of Persons with Disabilities on December 3, 2015, the primary objective of the campaign is to create a barrier-free and supportive environment for individuals with disabilities (Divyangjans) across the entire country.
- Volunteers play a crucial role in driving this initiative, actively participating in awareness campaigns, accessibility audits, and advocacy efforts. Their involvement in the Clean River (Ganga and Yamuna) campaign is also noteworthy.
Contribution of Individual Figures:
- Notable figures like Hellen Keller, an American author and activist, have played instrumental roles in changing perspectives about disability. Keller not only overcame her challenges but also tirelessly advocated for the rights of people with disabilities.
- The journey towards inclusivity has been guided by the wisdom and advocacy of thinkers and activists who have tirelessly worked to dismantle barriers and challenge societal attitudes.
- Figures like the late Stephen Hawking, a renowned theoretical physicist diagnosed with ALS, and great individuals like Beethoven, Pandit Hariprasad Chaurasia, Sudha Chandran, among others, demonstrate unparalleled dedication to their art despite physical obstacles.
Success Stories in the Sports Domain:
- In the realm of sports, the Paralympic Games showcase extraordinary feats by athletes with disabilities, exemplifying resilience and athletic prowess.
- Icons like Deepa Malik, paralyzed from the waist down, embody an indomitable spirit.
- India’s outstanding performance in the 2023 Asian Para Games, with 111 medals, including 29 gold, 31 silver, and 51 bronze, underscores the achievements of these remarkable sportspersons.
- Arunima Sinha’s determination in scaling Mount Everest with her prosthetic leg is also unforgettable.
Volunteerism serves as a catalyst for social change by fostering inclusivity and challenging societal norms. The commitment to the UN Convention on the Rights of Persons with Disabilities signals a global push for inclusivity, emphasizing the need for a shift in attitude to create a more equitable world.