Written by: Dr. Raymond Cruz
“With genetic engineering, we will be able to increase the complexity of our DNA, and improve the human race. But it will be a slow process, because one will have to wait … to see the effect of changes to the genetic code.” - Stephen Hawking
It is now possible: Gene therapy to treat diseases.
Previously thought of as science fiction, we are now at the threshold of modifying disease processes by altering the director of all cellular processes: the gene. Think about limiting damage from a typhoon by altering its wind speed and trajectory. Or slowing down an earthquake by “holding” land masses together to inhibit their movement. At least for this disease, we now have a new, innovative, and potentially life-changing weapon.
We now have a new, innovative, and potentially life-changing weapon.
Gene therapy can use a protein without triggering immune responses, known to hinder other therapeutic approaches. With their modified gene therapy approach, the research team engineered non-harmful viral vectors to deliver a ‘substitute’ protein for dystrophin – the defective protein in Duchenne Muscular Dystrophy (DMD). The synthetic substitute may be an effective and safe alternative, as it protects muscle in mice and dogs with naturally occurring mutations, including a large deletion that resembles the large dystrophin deletions found in humans.
Children born with Duchenne muscular dystrophy have a mutation on their dystrophin gene, the longest gene in the body. They cannot produce the protein dystrophin, because a functional gene is essential for proper formation of this protein. Skeletal and cardiac muscles become damaged as they repeatedly contract and relax with use. The damaged cells weaken and die over time, causing the characteristic muscle weakness and wasting and heart problems seen in Duchenne.
If the dystrophin gene could be replaced with a healthy gene, muscles would produce dystrophin and any further damage would be reduced.
At present, corticosteroids (similar to treatments given for asthma and other inflammatory diseases) are prescribed routinely to patients with DMD, and are now part of the recognized standard of care. Drugs to prevent the onset of heart failure are also prescribed. Patients with DMD also have reduced bone strength. In recent years, patients have been given bisphosphonate treatments such as zoledronic acid - used successfully to treat osteoporosis. All of these treatments treat the symptoms of DMD; they do not address the underlying cause, which is a lack of dystrophin.
How can we repair damaged genes? The biggest barrier to gene-based therapy is the fact that our cells have mechanisms to prevent intrusion of foreign molecules. To overcome this we use vectors, or carriers, to carry the new gene into the cell. Currently, the most promising approach is based on the use of a harmless virus called Adeno-associated virus (AAV) as a vector. Viruses have evolved to recognize certain cells and then insert themselves via the cell membrane, and deliver their genetic material into the cell. However, if scientists remove the unwanted, disease-causing genes and replace them with appropriate beneficial genes, they could restore gene expression. This is the basis of the ‘gene therapy’ that is causing great excitement at the moment.
Source: FDA.gov
Another approach could be the development of techniques involving the CRISPR /Cas9 system. Cas9 is an enzyme that can cut DNA at a precise location. CRISPR, a short strand of RNA (a chemical messenger similar to DNA) can complete the process of restoring the gene. Recent reports in the journal Science have used the CRISPR-Cas9 technique to treat mice with a defective dystrophin gene.
Source: Cambriddge.org
Like most medical treatments, gene therapy is not without risk. Viral vectors may induce unwanted immune system reactions. Wrong cells may also be targeted, causing tumors or cancer cells to develop. Finally, the viral vector itself may cause an infection in the host cell.
There are always risks and challenges when developing a new treatment. Regulators have strict scientific guidelines for clinical trials to ensure the intervention is as safe as it can be before tested on patients. One cannot underestimate the painstaking efforts of scientists and drug companies to come up with novel treatments for disease. It is a lengthy process, but it is worth pursuing. After all, such is the value of life.