Most traditional treatments today are designed using a one-size-fits-all to cover the “average” patient. But advances in biotechnology and Artificial intelligence (AI) medical researchers are now equipped with vast amounts of personalized datasets at their disposal, and can analyze unique situations based on our genetic profiles, family medical histories and other relevant medical conditions to better understand what types of therapies work best for each segments of the human population.
This laser targeted approach to healthcare is a huge deal, and billions are being invested to fund biologists, geneticists, computer scientists and experts in AI (artificial intelligence) to more accurately predict how specific genetic mutations around the world will respond to such personalized treatments. We are slowly building a map of the human genetic variations giving regenerative medical physicians better tools to craft medical therapies and achieve better response rates with less risk. The regeneration center offers functional medical programs using Genomics to customize nutrition and wellness recommendations based on each patients unique DNA profiles. Many new gene therapies currently being tested are not looking to correct the genetic defects direct but instead are looking to introduce a new copy of altered genes with the hopes of fixing the underlying issues.[1]
One example is research in Thailand on gene therapy for beta-thalassemia using modified globin genes. β-hemoglobinopathies such as β-thalassemia and sickle cell disease, are some of the most prevalent monogenic disorders around the world and quite frequent in Thailand where nearly 3,500 babies are born each year with beta-thalassemia disease. Severe, transfusion-dependent forms of the disease usually need regular blood transfusions throughout life. Even with previous treatment options, complications are frequent, and patient life expectancy is quite short. Researchers including the Institute of Personalized Genomics and Gene Therapy at Mahidol University in Thailand and Harvard Medical School reported early results of autologous gene therapy for thalassemia, and results from the first group of trial patients were published in The New England Journal of Medicine. Since then, gene therapies for transfusion-dependent beta-thalassemia have been approved in some countries, and long-term follow-up of treated patients continues.[2]
Other Areas Experimenting with Gene Therapies:
Autoimmune Diseases – Understanding the molecular basis of autoimmune conditions have helped create new modified gene therapies to treat affected patients who previously did not have
Anti-aging – Whether ageing should be treated as a disease is debated, and researchers are studying whether gene therapy could one day slow some age-related changes. Current Anti-aging treatments offer only slight benefits for men and women dealing with the aging process. Lifestyle measures such as regular exercise, a healthy diet, not smoking and good sleep have strong evidence for lowering the risk of many age-related diseases, while gene therapies for ageing remain experimental. In the Aging or sustained cell division process, telomeres act as natural buffers for wear and tear but eventually get too short and are unable to protect the chromosomes. When they get too short, cells stop dividing and enter a state called senescence, or sometimes die through programmed cell death, which contributes to what we call “aging.” Telomerase gene therapy has slowed some age-related changes in mice, but it has not been shown in clinical trials to slow aging or extend lifespan in people. Shorter telomere lengths have been shown to have a direct relationship with increased risk in cardiovascular diseases and many types of cancers including prostate cancer.
Hereditary Brain Disorders – Researchers are developing new treatments, including gene therapies using CRISPR gene editing, for rare inherited disorders and are studying whether they could help conditions such as Huntington’s disease and leukodystrophies that affect the white matter in the brain. One approach involves collecting blood-forming stem cells from the patient’s peripheral blood, editing their DNA in the laboratory with CRISPR-Cas 9 technology and returning the modified cells to the patient; these treatments remain experimental for most conditions, and there is no cure for Huntington’s disease.[5]
Cancer – The first CAR T-cell gene therapy was approved by the US FDA in 2017 for children and young adults up to 25 years old with acute lymphoblastic leukemia (ALL). Cancer immunotherapies are a new frontier in medical innovation & biotechnology. The treatments use the patient’s own cells then reprogram them to attacks the cancer cells in the patient’s body. NK cell therapies, used alone or as a combination treatment with NK cells and other therapies, are being studied in clinical trials for several cancers, including lung, prostate and pancreatic tumours, and results so far are early. Other types of diseases that are being targeted included squamous cell cancer of the neck, ovarian cancer, breast cancer, liver cancer, bladder cancer, and brain cancer.[6]
Other new gene therapies currently being tested are cancer vaccines. Vaccines require the collection of tumor cells directly from the patient and editing them with a specific genetic encoding that causes them to be much more visible to the immune system defense mechanisms. The modified cells are edited then reintroduced back into the patient along with immune-stimulating growth factors. The aim is for the patient’s immune system to recognize the modified cells and then attack similar cancer cells in the body that it previously ignored, although responses vary and most of these vaccines are still in clinical trials.
Vision Loss and Blindness – Until recently, the genetic cause of blindness have been untreatable. Gene therapy for inherited retinal disease works at the DNA level: a modified, harmless virus carries a working copy of the missing gene into retinal cells, usually by an injection under the retina. In suitable patients this can improve or stabilize some aspects of vision, but it does not reverse all vision loss. Luxturna (voretigene neparvovec) was approved by the US FDA in 2017 and in Europe in 2018 for people with inherited retinal disease caused by mutations in both copies of the RPE65 gene, which causes retinal cells to die over time and vision to be lost slowly. It is given as a one-time injection under the retina of each eye, and in its Phase III trial, improvements in functional vision were seen as early as 30 days after treatment.[7]
Lung Diseases and Hereditary Asthma – New pulmonary gene therapies are looking to treat idiopathic lung diseases that were caused by both genetic and environmental conditions.[8] One such treatment uses modified cells to ‘turn-off’ the bodies immune system response which results in allergic reactions to asthma or even food allergies. The current challenge or treating conditions due to allergies or asthma is that T-cells quickly develop a ‘memory’ making them resistant to traditional treatments methods. By altering the Immune T-Cells, doctors will be able to clean the memory of these cells allowing the immune system to tolerate the proteins that cause the undesired immune reactions. Other Gene therapies in clinical trials for Lung Diseases include:
- Cystic Fibrosis [9]
- Lung cancer [10]
- Chronic lung diseases such as COPD, Emphysema and IPF [11]
Gene therapy for lungs uses nucleic acids such as DNA or RNA as a delivery vehicle into the body to facilitate the desired expressions of proteins. Gene therapies are implemented using gene addition (gene replacement), gene repair or gene reprogramming. Currently, the most common treatments use Gene addition as the primary method of treating inherited genetic mutations.
Spinal Cord Injuries – Stitching Together Damaged Spinal Cords? Experimental new gene therapy is being tested in paralyzed mice helping them walk and grab again. When the spinal cord gets damaged, patients lose a little or all ability to control parts of the body and limbs. For most spinal cord injury patients’, patients with burst fractures, Spinal compression fractures, with and neurological conditions, the formation of scar tissue blocks the neural and nerve cells from communicating with the brain, each other and with any muscles that they control. A new spinal gene therapy looks to break down any scar tissue thus enabling neurogenesis at the site of allowing patients with control over their previously paralyzed limbs. For most patients treated for spinal cord injuries, recovering the use of hands is usually the top priority. If successful, the new gene therapy would allow such improvements in just a few weeks are enabling spinal cord injury patients to wash once again or dress independently and eat without assistance resulting in a significant improvement in the overall quality of life.[12]
Parkinson’s Disease – Levodopa (L-Dopa) remains the most effective medicine for Parkinson’s symptoms, but after several years many patients notice its effect wearing off between doses. Over time the medications become much
less predictable, and higher or more frequent doses can bring side effects such as involuntary movements (dyskinesia). One reason is that as Parkinson’s progresses, the brain loses more of the cells that contain the AADC enzyme (aromatic L-amino acid decarboxylase), which converts L-Dopa into dopamine. Unlike conventional studies, gene therapy for Parkinson’s uses a modified virus called adeno-associated viral vector (AAV) to carry the gene needed to produce AADC enzyme in the brain. The viral vector is then infused directly into a targeted area of the brain, the putamen, using MRI-guided surgery. MRI scans taken after treatment show new links formations between the cortical premotor, basal ganglia and motor regions.[13]
Multiple Sclerosis – Multiple sclerosis starts as an inflammatory disease which if left untreated turns into neurodegenerative disease. Gene therapy for MS and Ataxia allows modified allogeneic cells that help induce larger populations of regulatory cells such as markers CD4, CD25, and FOXP3 that are responsible for suppressing the inflammation. This new therapy for MS is still experimental, and it has not been shown to stop or reverse MS.
Tracking Changes in Cancers on a Global Level
Another advancement in epigenomics, genetics, and biotechnology is the study of cancers and how they mutate after traditional treatments. Understanding who or what turns our
genes on and off can help us understand how tumors mutate. Such knowledge is crucial for doctors so they can develop new immunotherapy protocols that are resistant to mutations allowing us to target tumor cells like ordinary and manageable chronic conditions.[14]
Every cell in the human body carries the same genetic coding however cells in the brain, heart, skin and bone function very differently based on the chemical signaling that can either activate or silence genetic expressions. This nature vs nurture response is unique and challenging to predict patient to patient. Changes in this signaling are thought to contribute to many diseases, including diabetes, lung cancers and neurological conditions such as Alzheimer’s and MND, together with inherited, environmental and lifestyle factors. Learn more in the stem cell glossary.
Understanding these unique circumstances on the molecular level gives doctors the power to find the optimal options for each condition the patient might be facing and how they might respond to particular treatment even before the procedure begins.
The Beginning of Precision Medicine
The challenge for gene and exosome therapies is finding ways to administer a very complex, life-saving treatment in an affordable manner and especially in areas of the world where healthcare is limited, to begin with. Although cord blood and marrow stem cell transplants exist throughout the world, the ability to sequence genes in an efficient way is not widely available.
There is a sound humanitarian argument in favor of funding and building more gene therapy trials around the globe. Beta thalassemia and sickle cell disease are very expensive to treat over the long term of a patient’s life, and one-time gene therapies now approved in some countries aim to reduce or remove the need for lifelong treatment, although long-term outcomes are still being studied. These genetic diseases result in life long disability and often result in early death. Science and medical researchers have once again found solutions to previously impossible conditions and will continue to do so if we make healthcare a priority.
Published Clinical Citations
[1] ^ Cappa, Ryan, Liana Theroux, and J Nicholas Brenton. 2017. Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach. Pediatric neurology (July 13). doi:S0887-8994(17)30297-7. https://www.ncbi.nlm.nih.gov/pubmed/28843454
[2] ^ Cha, Charles W, and Scott D Boden. 2003. Gene therapy applications for spine fusion. Spine, no. 15 Suppl ( 1). https://www.ncbi.nlm.nih.gov/pubmed/12897478
[3] ^ Chen, Y, V K Kuchroo, J Inobe, D A Hafler, and H L Weiner. 1994. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science (New York, N.Y.), no. 5176 ( 26). https://www.ncbi.nlm.nih.gov/pubmed/7520605
[4] ^ Choong, Chi-Jing, Kousuke Baba, and Hideki Mochizuki. 2015. Gene therapy for neurological disorders. Expert opinion on biological therapy, no. 2 (December 5). doi:10.1517/14712598.2016.1114096. https://www.ncbi.nlm.nih.gov/pubmed/ 26642082
[5] ^ Choong, Chi-Jing, and Hideki Mochizuki. 2016. Gene therapy targeting mitochondrial pathway in Parkinson’s disease. Journal of neural transmission (Vienna, Austria : 1996), no. 2 (September 16). doi:10.1007/s00702-016-1616-4. https://www.ncbi.nlm.nih.gov/pubmed/27638713
[6] ^ Cmielewski, Patricia, Nigel Farrow, Sharnna Devereux, David Parsons, and Martin Donnelley. 2017. Gene therapy for Cystic Fibrosis: Improved delivery techniques and conditioning with lysophosphatidylcholine enhance lentiviral gene transfer in mouse lung airways. Experimental lung research, no. 9-10 (December 13). doi:10.1080/01902148.2017.1395931. https://www.ncbi.nlm.nih.gov/pubmed/29236544.
[7] ^ Dalkara, Deniz, Olivier Goureau, Katia Marazova, and José-Alain Sahel. 2016. Let There Be Light: Gene and Cell Therapy for Blindness. Human gene therapy, no. 2. doi:10.1089/hum.2015.147. https://www.ncbi.nlm.nih.gov/pubmed/ 26751519.
[8] ^ Husain, S R, J Han, P Au, K Shannon, and R K Puri. 2015. Gene therapy for cancer: regulatory considerations for approval. Cancer gene therapy, no. 12 (November 20). doi:10.1038/cgt.2015.58. https://www.ncbi.nlm.nih.gov/pubmed/26584531.
[9] ^ Kim, Namho, Gregg A Duncan, Justin Hanes, and Jung Soo Suk. 2016. Barriers to inhaled gene therapy of obstructive lung diseases: A review. Journal of controlled release : official journal of the Controlled Release Society (May 16). doi:S0168-3659(16)30310-8. https://www.ncbi.nlm.nih.gov/pubmed/ 27196742.
[10] ^ Biasco, Luca. 2017. Integration Site Analysis in Gene Therapy Patients: Expectations and Reality. Human gene therapy, no. 12 (December 0). doi:10.1089/hum.2017.183. https://www.ncbi.nlm.nih.gov/pubmed/29160103
[11] ^ Lara-Guerra, Humberto, and Jack A Roth. 2016. Gene Therapy for Lung Cancer. Critical reviews in oncogenesis, no. 1-2. doi:10.1615/CritRevOncog.2016016084. https://www.ncbi.nlm.nih.gov/pubmed/27481008.
[12] ^ Macer, D R, S Akiyama, A T Alora, Y Asada, J Azariah, H Azariah, M V Boost, P Chatwachirawong, Y Kato, and V Kaushik. 1995. International perceptions and approval of gene therapy. Human gene therapy, no. 6. https://www.ncbi.nlm.nih.gov/pubmed/7548279.
[13] ^ Stabler, Collin T, and Edward E Morrisey. 2016. Developmental pathways in lung regeneration. Cell and tissue research, no. 3 (December 13). doi:10.1007/s00441-016-2537-0. https://www.ncbi.nlm.nih.gov/pubmed/27957616
[14] ^ Wirth, Thomas, Nigel Parker, and Seppo Ylä-Herttuala. 2013. History of gene therapy. Gene, no. 2 (April 23). doi:10.1016/j.gene.2013.03.137. https://www.ncbi.nlm.nih.gov/pubmed/23618815