“Doctors won’t make you healthy. Nutritionists won’t make you slim. Teachers won’t make you smart. Gurus won’t make you calm. Mentors won’t make you rich. Trainers won’t make you fit. Ultimately, you have to take responsibility. Save yourself.”- Naval Ravikant
As medical innovation evolves, one of the emerging treatments involves the utilization of gene therapy to treat the patient from within. The advances in the field are influenced by the discovery of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins. As genetic research utilizing these compounds increases, the approaches to gene therapy are being constantly upgraded.
Gene therapy as a method does have some limitations that the utilization of CRISPR is able to overcome. The primary concerns for the therapy include the utilization of viral vector delivery, which can expose the patient to conditions such as immunogenic toxicity. CRISPR does not cause these conditions, and is welcome in the gene therapy realm because of advantages such as these.
The coronavirus has generated a global pandemic that has led to states of emergencies everywhere. With the current need for fast and efficient testing tools for diagnosis, the preventative route is being sought at this point in time. Current tests have their limitations, including the time to result, as well as the tests accuracy and sensitivity to the virus. With molecular testing and serological testing as the primary testing methods, the two methods are both with efficacy limitations that can lead to incorrect readings during testing. With CRISPR Cas 12, an assay was created for the detection of COVID-19. The test has the advantages of 40 minutes of testing time, with a 95% accuracy of test results.
As an excellent diagnostic tool, CRISPR will also provide a means to treat COVID-19 patients via the utilization of Cas13. Cas13 has a mechanism that is able to target the coronavirus. As a proven system, the utilization of CRISPR/Cas will be one of the methods that we can identify a solution to the current global pandemic.
Is Gene Therapy Applicable To The Orthopaedic Sphere?
With the aforementioned advent of therapies within the biologic realm, the focus of medicine now and in the future is to actually facilitate internal healing of the body. With increasing studies of how healing mechanisms are carried out in the body, it will be possible for the appropriate levers to be pulled, that will facilitate the enhancement, or even acceleration of the healing process in the human body.
One of the focus areas of internal healing is via the utilization of technologies such as gene therapy. Designed to introduce genetic materials into cells, as a means to compensate for any abnormalities in the genes, or to ensure that beneficial genes are being manufactured by an organism, gene therapy is really high level engineering that will facilitate future biological changes within a living system.
Genes are the underlying foundation of our human existence. Understanding their mechanisms will be the key to ensuring that the appropriate functional proteins are being generated by a system. If a gene with an appropriate carrier vector is delivered into a cell, it will be able to carry out its necessary functions. The utilization of modified viruses is one such way that a new gene can be delivered into a cell. Alternative methods also include the introduction of the genes to some extracted cells from a patient, in a laboratory. Once the genes have been introduced to the cells, after the appropriate incubation period, they will be returned to the patient.
While gene therapy is still in its infancy, there is still lots to be learned in order to ensure that the full mechanisms and applications of the therapy can be applied to the treatment of cases. Within the orthopaedic realm, there is ongoing research being carried out, to ensure that the applications of gene therapy can be facilitated.
Orthopaedic Gene Therapy
Orthopaedic Gene Therapy is an area of study that has spanned a few decades. Scientific studies have indicated that with the previous work that was done, there have been successful preclinical trials, and as a result the future for orthopaedic applications of genetic therapies looks very promising. At this point in time, many therapies that are under study are in the process of achieving FDA approval. Because of the underlying uncertainties that are associated with gene therapy, the track to FDA approval is still being worked on. There is still a lot to be learned about gene therapy, and as a result, the FDA often views the research as unsafe and risky. For projects that are deemed as having little ROI, the pharmaceutical industry will not be inclined to fund such activities.
Of course, the beauty of science and technology is that it is possible to self fund activities. Many start up companies have decided to challenge themselves to actually do the research that will enable the field to progress. Being bold enough to take on such critical challenges in the medical realm will only reap great rewards for those who are able to master the healing mechanisms.
The successful accomplishment of gene therapy will require the close interaction of scientists, clinicians and the regulatory bodies who will facilitate the approval and distribution to the masses. Science and technology is a realm that takes decades for success. With a little focus, perseverance and determination however, there will be a possibility for success. This has been revealed and documented in all realms of the scientific sphere. In the aerospace industry for instance, many of the rockets that are currently being deployed, were under construction for years before they were finally fit for orbit. The medical realm shouldn’t expect itself to be any different. There will be constraints, but nothing that will be impossible in the long run. Gene therapy is a very promising area of research, and with a sense of optimism, the orthopaedic realm will definitely benefit from the upsurge in the field.
How does Gene Therapy Work?
Via the ability to modify genes, it will be possible for mutations to be eliminated within a living organism. With the utilization of vectors, gene transfer will allow the therapeutic genes to enter a living system. Once in the living cell, the appropriate level and duration of transgene expression will be facilitated. Scientific studies have now facilitated the improvement in the knowledge of the level and duration of transgene expression. Via the utilization of biological promoters and other regulatory mechanisms, it will be possible to achieve the desired outcome.
What Orthopaedic conditions are treatable by Gene Therapy?
Four main areas of orthopaedic research have been found to be useful for the application of Gene Therapy in the orthopaedic realm. These four areas include:
Mendelian disorders
Tumors
Arthritis and other Joint Diseases
Tissue Repair and Regenerative Medicine
Additional Genetic Diseases
Arthritis is one of those areas that is statistically highest in the orthopaedic realm. With the ability to directly inject the critical gene modifiers into the diseased joints, it is possible to monitor any improvements in the healing process. Arthritis is a joint ailment, and the joint cavity does provide the space to inject healing solutions such as gene modifiers and even stem cells. The mechanism of the joint, with the synovium a joint component that allows gene delivery, the gene vectors will engage with the synovial cells and the interaction will start the gene modification process.
Once the synovial cells are genetically modified, the synovial cells can then start a new expression, and deliver the appropriate transgene products into the joint. The enhanced healing of the arthritic joint can then be facilitated, and the joint will heal itself.
With arthritis being such a prevalent condition, improving the health of patients with this condition will have great advantages in the medical realm.
Tissue Engineering and Regenerative Medicine
Another statistically high orthopaedic occurrence is that of the sports injury. During sports injuries, various soft tissues are impacted in a patient, and their healing time may range depending on the material. While tissues like cartilage can repair relatively fast, there are other hard materials such as bone that takes a longer time to repair, and often requires some scaffolding to hold the joint in place while the system is regenerating itself.
Orthopaedic gene therapy is a technology that can benefit the patient. With an improved understanding of the repair processes that are involved in healing a joint, it will be possible to start the healing process either in the laboratory or in vivo. Current studies have identified the appropriate carriers for healing agents of tissue and bone, and the appropriate healing mechanisms are being studied and trialled. There is always a pressing need to heal bone, and soft tissues such as tendons and ligaments. With the appropriate clinical trials, anticipation of treatment to patients will one day be available.
In conclusion, the orthopaedic realm is still a place with lots of potential to grow and develop. Once successful, the treatment of conditions such as arthritis and bone healing will be facilitated via this method. With orthobiologics, the sky is still the limit. Science and technology is always an area that is growing and evolving. Talk to your orthopaedic surgeon about treatments today that you can trial.
References:
- Orthopaedic Gene Therapy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264489/
- CRISPR Gene Therapy: https://www.frontiersin.org/articles/10.3389/fonc.2020.01387/full