The burden of proof is on the drug company to demonstrate the quality of medical benefit their gene therapy delivers. That said, I am in favor of using a cost-effective approach when approaching the issue.
Most concerns center on potentially poorer quality and outcomes of care from limited access to mental health specialists, reduced length of inpatient care, and reductions in intensity of outpatient mental health services Mechanic, ; Mechanic, The burden of proof is on the drug company to demonstrate the quality of medical benefit their gene therapy delivers. Clinical Case Studies. Some inmates only get out of their cell when they seek health care. About 60—70 percent of respondents in large, community-based surveys say they are worried about cost Sturm and Sherbourne, ; Sussman et al. First identify the gene missing from a sick patient.
These metrics keep the focus of appropriate drug price centered on patient experience and the quality of medical outcome. Footnote: Many gene therapies target rare diseases. For this reason, a fair price based on traditional, cost-effectiveness calculations may not be sufficient motivation for a company to commit capital towards certain rare diseases. In these scenarios, either the CE equation needs to be tweaked or additional incentives should be provided in order to maintain innovation in these disease areas. When optimizing the efficacy of a new drug, a central challenge is the search for minimum effective dose MED.
These proteins need to be functional and actually fix the cellular deficiency that is responsible for the genetic disorder. As you increase the intensity of the gene therapy viral load , you should be inserting more genetic material for the deficient protein into the necessary cells. However, an excessively high viral load can cause toxicity issues liver damage, hyper-activated immune system. So, an ideal gene therapy protocol will administer the minimum effective dose of virus. This ideal viral dose will generate a protein level sufficient to eliminate all symptoms of the genetic disorder — and it will do so without triggering a toxic reaction to the virus.
We currently see the quest for minimum effective dose in the hemophilia space. Multiple companies Spark, Sangamo, BioMarin, etc. Hemophilia is a genetic disorder caused by a missing or defective clotting protein.
The disorder is passed down from parents to children, however about a third of all cases are caused by somatic mutations. About 1 in babies are born with hemophilia, resulting in about 20, hemophiliacs in the US. Hemophilia A is 4 times more common than hemophilia B. Spark is one of the front-runners in the quest to develop an approved gene therapy for hemophilia A. Like most companies, Spark is monitoring a dose-dependent response. A dose-dependent experiment will test multiple dosages and examine results for efficacy and safety.
Dose-dependent experiments allow a company to explore their MED minimum effective dose. In August, ALT is a readout for problems with the liver. Alanine aminotransferase is an enzyme released by the liver when the liver is in trouble.
When physicians observe patients struggling with a toxic reaction to a therapy, they administer steroids to lessen the effect. The long term goal is a cure for hemophilia. To reach that goal, companies need to optimize many experimental variables, including MED. When we look ahead to the future of gene therapy. In the case of hemophilia, a gene therapy must boost factor VII protein levels in the blood to the point where bleeding events are severely reduced, possibly eliminated. Furthermore, this outcome must occur in the absence of a toxic reaction, i. The genome edits seemed to work, but dosage should be increased and the transgene should be optimized for potency.
However — keep in mind, this trial represents the first genome edits delivered to a live human. Sangamo made a historic step. They did not, however, make a clinically significant step. The science, the history and the future of gene therapy.
The gene therapy sector is experiencing an acceleration. In this article, I attempt to make sense of this world. I provide a brief background on the science and then discuss both the history and the future of gene therapy.
All of this seems to be changing. Here is a list of topics discussed below. Click on a topic to jump straight to that section. Click an icon below to share page with friends. Introduction to gene therapy Gene therapy is the use of genetic modification to treat human disease. The general strategy of gene therapy is relatively straightforward. Identify the genetic cause of a disease. In a laboratory, cut and paste some DNA so as to create a genetic fix for the problem. Importance of the virus in gene therapy.
Semantics aside, viruses are dangerous and have been killing people since the dawn of humanity HIV, Polio, Spanish flu, small pox In an interesting turn of fate, viruses are now being employed by the medical community as a means to save human lives. The basic concept is simple… Identify the gene that is missing in a patient suffering from a genetic disease. Install this gene into the DNA of a modified virus. A modified virus is no longer dangerous but can still infect cells. Allow this modified virus to infect the cells of the sick patient.
These infected cells now contain a copy of the missing gene. Symptoms of the genetic disease begin to disappear. The disease is considered cured. Using a virus to conduct gene therapy is a classic example of scientists co-opting i. Common forms of virus used for gene therapy. Retrovirus Many early gene therapy experiments used a type of virus called a retrovirus. Adeno-associated virus Recently, many gene therapy trials are conducted with a virus called an AAV adeno-associated virus. AAV is a small virus that infects humans and some monkeys. AAV has become the preferred virus for the following reasons: only causes a mild immune response infects both dividing and non-dividing cells persists in cells without directly inserting into the host genome remains in an extra-chromosomal state.
Challenges in the implementation of gene therapy Scientist have been trying to insert missing genes into sick patients for about 40 years. Figuring out the best virus to use. I mentioned the virus needs to be modified before its used to deliver a gene safely. Its been tricky learning exactly how to make a virus safe and non-toxic for patients. Immune rejection. Our body is designed to reject and attack foreign DNA. Great lengths have been taken to reduce or eliminate any harmful immune response our body may generate in response to gene therapy.
Creating a long term cure. Once the missing gene is inserted into our body, that gene may not stick around for long. Dividing cells may eventually stop reproducing the inserted gene. In that sense, the therapy is diluted out. This means the patient requires multiple treatments. Many diseases are caused by multiple genes. In fact, most inherited diseases are the cause of multiple genes.
This complicates the gene delivery strategy. Delivering 1 gene is tricky… delivering 8 genes is very tricky. Ethical issues. Before moving forward with a therapy, you need to demonstrate that your proposed DNA modification is not germline sperm or egg modification. Inserting the gene in the right place.
If your gene therapy strategy inserts the missing gene on top of another critical gene, then that critical gene becomes mutated and non-functional. High cost of therapy. As you may imagine, almost nobody could afford the cure. The science has come a long way since Now, we need to figure out a reasonable pricing system. Q : How did we get to approved gene therapies? Below, I summarize the significant milestones along the way. The s… In , a key scientific experiment revealed that DNA could be injected into human cells and that this injected DNA could fix a biological problem in those cells Merril, The s… In the s , scientists such as Martin Cline and French Anderson, were learning how to use viruses to deliver DNA into human or mouse cells.
The s… In this report from NCI in Bethesda, scientists removed white blood cells from patients with advanced melanoma.
Sickle cell anemia modified umbilical stem cell cord blood, ref. Okay — by now you should have a solid understanding of the history of gene therapy and how gene therapy works. Now, I will share my thoughts on the future of gene therapy. Future of gene therapy The future is unwritten. Scroll down or click on a topic to jump straight to that section.
Sidenote: The number of companies pursuing gene therapies has rapidly increased. What is a fair price for gene therapy? If gene therapy delivers a cure…how much is that cure worth? Are organ transplant prices indicative of the cost of future gene therapies? In this regard, healthcare is fundamentally different than other industries. Yet, at the same time…drug manufacturers must be incentivized. So, where does this leave us? Below, I examine this question from three different paradigms. Determine the cost of not treating the genetic disorder.
Price your gene therapy under that number. Price your gene therapy as competitive to a preexisting treatment for the same disease. Use a cost-effective ratio to set price based on the number of quality-adjusted life years a therapy delivers. Leerink analysts wrote the following: It appears the seemingly impervious million-dollar threshold may be breached with hemophilia gene therapy, which could do so while still creating value for society by reducing the cost of factor replacement therapy. Ok, so how do we arrive at the numbers for this ratio.
Hoarding disorder. New England Journal of Medicine. Mataix-Cols D, et al. Hoarding disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis.
Treatment of hoarding disorder in adults. Phillips KA, et al. Merck Manual Professional Version. Brakoulias V, et al. A meta-analysis of the response of pathological hoarding to pharmacotherapy. Psychiatry Research. Tolin DF, et al. Cognitive behavioral therapy for hoarding disorder: A meta-analysis. Depression and Anxiety. Ale CM, et al. Family-based behavioral treatment of pediatric compulsive hoarding: A case example. Clinical Case Studies. Morris SH, et al.
Hoarding in children and adolescents: A review. Child Psychiatry and Human Development. Sawchuk CN expert opinion. Mayo Clinic, Rochester, Minn.
March 1, Mayo Clinic Marketplace Check out these best-sellers and special offers on books and newsletters from Mayo Clinic. Adopt a diet rich in whole grains, fruits, vegetables, lean meats, skinless poultry and non-fried fish, and low-fat or fat-free dairy products. Avoid processed foods, which are often high in saturated and trans fats, sodium and added sugar. Get active. Incorporate at least minutes of moderately vigorous physical activity into your weekly routine. Walking is the easiest place to start, but you may want to experiment to find something else you like to do that gets your heart rate up.
If needed, break your exercise up into several short, sessions throughout the day to reach your goal.