Neurologic Paediatric Disease and Gene Therapy

Renée Shellhaas^*
*Correspondence: Renée Shellhaas, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA, Email:

Keywords

Child neurology • Disparities • Diagnosis • Gene therapy • Rare disease • Ethics • Health economics • Antisense oligonucleotide

Introduction

Just picture your kid hitting a baseball through the windshield of one of your neighbours. What options do you have? You may dismiss the problem by denying that your youngster smashed the windshield. With one of the convenient tool kits from an auto repair company, you may stop more windshield cracks from forming, but this is not a long-term fix. Finally, you might install a brand-new, functional windshield in place of the old one. So what does the discussion about cracked windshields have to do with gene therapy technology? A hereditary disease or problem can easily be compared to a "cracked windshield." Numerous medical conditions or genetic illnesses are brought on by mistakes or mutations in one or more specific genes. Consequently, the potential of gene therapy is comparable to the remedies mentioned in the case of fixing a cracked windshield or a damaged gene. Nothing is restored if the choice is to keep mute and provide no assistance: The genetic condition or deficiency will cause the patient's death. The patient will live if it is decided to offer adjunct therapy, similar to a repair kit in the windshield, but frequently, consequences from the hereditary condition still exist. The issue, however, will be resolved if the choice is made to delete the dysfunctional gene and replace it with a completely new, functional gene.

Description

Cardiomyopathy is a chronic, frequently progressive condition with severe morbidity that affects newborns and children. Cardiomyopathy most usually has genetic or infectious etiologies in the paediatric population. Even while there are comparable clinical groups of cardiomyopathy, there is more variation in the genetic reasons than is observed in the adult population.

After years of failures, gene therapy (GT) is now making significant strides. Since 2017, five GTs have obtained US regulatory clearance and more than 900 more are now under development. Since there are few viable therapies for many of these uncommon paediatric disorders, they substantially shorten patients' lives. Specific ethical issues in three areas—assessing hazards and possible benefits, equitably choosing participants and interacting with patient communities—remain unsolved as these GTs reach early-phase clinical trials. We examine these ethical issues and provide considerations for future GT studies by drawing on our experience as clinical investigators, fundamental scientists and bioethicists engaged in a first-in-human GT experiment for an ultrarare paediatric illness.

Creating healthy Manacells from autologous blood and using it to treat paediatric cases. With the use of unique methods and materials, a gene treatment procedure has been developed. Exon shuffling, modifications to cisregulatory regions, horizontal transfer, cell fusions and entire genome doubling are just a few examples of the significant mobile DNA activities and massive genome remodelling events that have been revealed by genome sequencing during critical points in evolution. Multiple triggers, including microbial infection, interspecific hybridization that results in the generation of allotetraploids and events comparable to those documented in the DNA record, activate the natural genetic engineering processes that mediate genome restructuring. These molecular genetic findings, along with an analysis of how mobile DNA rearrangements boost the effectiveness of producing fresh functional genomic sequences, enable the formulation of an interactive evolutionary processes perspective for the twenty-first century. This perspective combines traditional cytogenetic knowledge of the function of hybridization in species diversification with modern knowledge of the molecular basis of genetic change, significant genome events in evolution and triggers that activate DNA restructuring. When particular stimuli help the patients' DNA undergo a hybridization procedure, it is now feasible to really see the DNA remodelling under the microscope thanks to this clear knowledge. The patient's serum already has the final imprint of the DNA that needs to be reconstructed; these properties are reinforced when the DNA is injected into the patient's body. We have long known about TRANSPOSONS, which are transposable elements or sequences that may move across the genome through a process known as transposition (McClintock Nobel Prize 1993). They stand for a strong force for genomic change. They might be a significant source of mutation. If the transposon is completely removed, these alterations may occasionally be fully reversible. Simple transposon elements are the transcription and translation termination signals, promoters and genes that encode the transposase enzyme, which catalyses transposition. Short inverted repetitions are always present on each side of the insertion sequence.

Each insertion sequence has between 800 and 2000 nucleotides and is transposed conservatively, which means that it is removed from one site and moved to a different location without being replicated. Transposes precisely cleaves at the ends of the insertion sequence's inverted repetitions and makes staggered cuts to the target sequence as well. The target sequence's overhanging ends are subsequently joined to the transposable element by the transposes enzyme. Using DNA polymerase and DNA ligase, the transposon's short single-stranded DNA segment on both sides is eventually repaired. A brief direct repetition of the target sequence that flanks the transposon is always produced by transposition.

So long as it is flanked by insertion sequences, any type of DNA sequence can be a component of a transposon and migrate across the genome. However, transposons' mutations are what trigger evolution [1-5].

Conclusion

The paediatric neurology community can play a crucial role in guiding and implementing gene-targeted therapeutics for neurological illnesses since they are still in their early stages of development. This responsibility include assisting in the creation of infrastructure and rules, guaranteeing the ethical, effective and fair use of therapies and lobbying for universal access that is both inexpensive and widespread for all children.

Acknowledgement

None.

Conflict of Interest

The author shows no conflict of interest towards this manuscript.

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