Written By Vrinda Somisetty
1.1 Autism Spectrum Disorder (ASD)
Autism spectrum disorder (ASD) is a developmental disability caused by differences in the brain. Some people with ASD have a known difference, such as a genetic condition. Other causes are not yet known. Scientists believe multiple causes of ASD act together to change the most common ways people develop. We still have much to learn about these causes and how they impact people with ASD (CDC).
People with ASD may behave, communicate, interact, and learn in ways that are different from most other people. There is often nothing about how they look that sets them apart from other people. The abilities of people with ASD can vary significantly. For example, some people with ASD may have advanced conversation skills whereas others may be nonverbal. Some people with ASD need a lot of help in their daily lives; others can work and live with little to no support. ASD begins before the age of 3 years and can last throughout a person’s life, although symptoms may improve over time. Some children show ASD symptoms within the first 12 months of life. In others, symptoms may not show up until 24 months of age or later. Some children with ASD gain new skills and meet developmental milestones until around 18 to 24 months of age, and then they stop gaining new skills or lose the skills they once had.
As children with ASD become adolescents and young adults, they may have difficulties developing and maintaining friendships, communicating with peers and adults, or understanding what behaviors are expected in school or on the job. They may come to the attention of healthcare providers because they also have conditions such as anxiety, depression, or attention-deficit/hyperactivity disorder, which occur more often in people with ASD than in people without ASD (CDC).
1.2 CRISPR-Cas9 Technology
Autism Spectrum Disorder occurs in about 2 to 4 percent of people with ASD, rare gene mutations or chromosome abnormalities are thought to be the cause of the condition, often as a feature of syndromes that also involve additional signs and symptoms affecting various parts of the body. For example, mutations in the ADNP gene cause a disorder called ADNP syndrome. In addition to ASD and intellectual disability, this condition involves distinctive facial features and a wide variety of other signs and symptoms. Some of the other genes in which rare mutations are associated with ASD, often with other signs and symptoms, are ARID1B, ASH1L, CHD2, CHD8, DYRK1A, POGZ, SHANK3, and SYNGAP1. In most individuals with ASD caused by rare gene mutations, the mutations occur in only a single gene (“Autism Spectrum Disorder: MedlinePlus Genetics”).
However, a well-established model and perfect treatment for this spectrum disease have not been discovered. The rising era of the clustered regularly interspaced palindromic repeats (CRISPR)-associated protein 9 (Cas9) system can streamline the complexity underlying the pathogenesis of ASD (Sandhu et al.). CRISPR/Cas9 is a gene-editing technology that involves two essential components: a guide RNA to match a desired target gene, and Cas9 (CRISPR-associated protein 9)—an endonuclease that causes a double-stranded DNA break, allowing modifications to the genome. One of the most exciting applications of CRISPR/Cas9 is its potential use to treat genetic disorders caused by single gene mutations. Examples of such diseases include cystic fibrosis (CF), Duchenne's muscular dystrophy (DMD), and hemoglobinopathies. The approach so far has currently only been validated in preclinical models, but there is hope it can soon be translated into clinical practice (Redman et al.).
1.3 Ethical Considerations
The process of gene editing interferes with the natural identity of individuals due to the manipulation of human germline cells, becoming a matter of public concern, specifically in the case of ethics. Compared to early genetic clinical research yielding reported adverse outcomes, CRISPR treatment has benefits in terms of financial burden and simplicity. However, the assumption of therapeutic use has taken a toll on fundamental clinical research in a clinical setting. For instance, despite the success of editing genomes non-pathogenically, the pathogenic variants that existed in the brain for long periods may have long-term adverse effects, which, in turn, will halt the intervention of CRISPR to reduce such symptoms (Farrell et al.). However, the use of CRISPR treatment is much more prevalent in the therapeutic approach to curing HIV or herpes infections. Despite the reported clinical trial identifying a cure strategy, additional ethical considerations and practices are required, for instance by including historically marginalized individuals and clinical groups (Dubé et al.). A related idea is "solidarity," which is the phenomenon of pursuing the common good (Mulvihill et al.).
Human potential and current vulnerabilities, as well as fostering intergenerational mutuality and taking into account the benefits and risks of experimentation, should all be taken into account when changing the human genome for the benefit of society. Genetic tools like CRISPR-Cas9, which support the affirmation of successful human research, are proponents of creating the framework for solidarity. The underlying idea is that genetic research and treatment should be carried out for the benefit of the public and the greater good rather than for fame and financial gain. Once more, solidarity is based on equally sharing expenses without taking advantage of ownership or profits. The importance of ethics in any treatment from such a perspective is highlighted by the distribution of crucial information to stakeholders and patients rather than the general public.
The early developmental stages of an individual, which cover the first two years after birth, are when autism symptoms can be seen. Early detection and intervention can help to improve the genetically predisposed or environmental causes of autism. Even though the only way to diagnose ASD is with clinical standard tests, the condition necessitates extensive therapy and the associated costs. To increase the accuracy and speed of diagnosis, ASD can also be assessed in children using a variety of machine-learning techniques, such as Logistic Regression. Even so, the clinical application of CRISPR therapy forces parents of minors to choose whether or not to proceed with such treatment.
1.4 Future Implications
Nevertheless, gene therapies like CRISPR are growing more common in a variety of medical specialties, and some have even been successful in treating certain diseases. For instance, voretigene neparvovecrzyl, which was sold under the brand name Luxurtna and received FDA approval, was used to treat any heritable retinal dystrophy brought on by a mutated RPE65 gene. Even though it was claimed that each injection cost $425,000, this was not the main factor in some patients' inability to receive the gene swap. According to reports, a three-year follow-up showed that all 20 patients who had received Luxurtna treatment had kept their vision, and a five-year follow-up showed similar positive outcomes. Furthermore, three months of treatment with precision editing, such as CTC001, for patients with blood disorders like beta thalassemia has resulted in improved hemoglobin levels and a reduction in the need for blood transfusions. Seven patients with severe sickle cell disease who received the same treatment showed comparable outcomes. Additionally, nusinersen, sold under the brand name Spinraza, was used to treat patients with spinal muscular atrophy for an initial $750,000 cost and a subsequent $375,000 annual cost. Spinraza has improved motor function and can support children in living longer, more active lives, even though it cannot restore normal function. Medical professionals can delay the onset of that disease for years when a newborn receives a genetic diagnosis as a result of screening (Daley). As mentioned, reported trials have yielded positive outcomes, despite the costs of therapy and medications, CRISPR treatment for Autism Spectrum Disorder (ASD) has the potential to succumb to a new future through machine learning techniques and the concept of the public good.
References
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Autistic Spectrum Disorder - Lanc UK. (n.d.). Learning Assessment and Neurocare Centre. Retrieved December 31, 2023, from https://www.lanc.org.uk/related-conditions/autistic-spectrum-difficulties-asd-adhd/
Daley, J. (2021, November 1). Four Success Stories in Gene Therapy. Scientific American. Retrieved December 31, 2023, from https://www.scientificamerican.com/article/four-success-stories-in-gene-therapy/
Ethical and practical considerations for cell and gene therapy toward an HIV cure: findings from a qualitative in-depth interview study in the United States - BMC Medical Ethics. (2022, April 9). BMC Medical Ethics. Retrieved December 31, 2023, from https://bmcmedethics.biomedcentral.com/articles/10.1186/s12910-022-00780-1
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Saunders, M. (2018, July 10). Disability Rights Activists Raise Concerns Over Genetic Editing for Autism. The Globe Post. Retrieved December 31, 2023, from https://theglobepost.com/2018/07/10/genetic-editing-autism-disability/
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