In this week’s bumper edition, we discuss the latest CRISPR developments in human embryos and pig organs, a computer chip that can reprogram skin cells, new insights into Parkinson’s Disease, questions about antibiotic treatment guidance and how transparent pharma companies are being with clinical trial data.
Inherited cardiac disease deleted from embryos
In another step forward for CRISPR, the gene editing tool was successfully used to remove a faulty gene in embryos that would otherwise result in hypertrophic cardiomyopathy, a disease in which the heart can suddenly stop beating. The study, published in Nature, used IVF with mutated sperm and healthy eggs. CRISPR was used to disrupt the faulty gene from the sperm, which was then replaced by the healthy version of the gene from the egg following fertilization. CRISPR normally detects a gene sequence and replaces it, so this method is slightly different as it caused the gene to instead be identified as faulty and thus the healthy copy was selected instead.
The results were successful in 72% of the embryos, meaning the faulty gene was completely eradicated from all future generations. “Mosaicism,” whereby embryos contain cells with both mutated and non-mutated genes, was avoided, demonstrating the need to interfere early in development. This study could pave the way for combatting inherited diseases, e.g., cystic fibrosis, in the future, however long-term safety would need to be established and ethical questions surrounding editing of human embryos remains a controversial subject.
Coincidentally, a day after this news, the American Society of Human Genetics and the American Society for Reproductive Medicine published guidelines for germline genome editing.
CRISPR may enable pig organ use in humans
In a second landmark development, CRISPR was used to alter pig DNA to potentially enable use of pig organs in humans. Many pig organs are of similar size/function to human organs and could provide a solution to the organ donation shortage. However, pigs cells contain viruses called porcine endogenous retroviruses (unfortunately called PERVs), which can transfer to human cells and may result in diseases such as cancer. In the study, reported in Science, CRISPR was used to remove PERVs from pig cells in a dish, and then the cell content was transferred into embryos and implanted into hosts. 37 PERV-free pig clones were successfully born.
The pigs could still contain other viruses that may transfer to humans, but this is a major step forward in making them more compatible, overcoming a long-standing hurdle in their use. The team plans to further alter the pig cells to make them less likely to be rejected by the human immune system and initial tests in primates would be required prior to the first human transplant, meaning it may be some time before becoming a reality.
Groundbreaking Sci-Fi-like chip reprograms skin cells
It sounds like something out of a futuristic sci-fi movie – a small chip placed on the skin that can stimulate skin cells to turn into any type of cell, rescuing diseased or dying tissue. The technology, however, is real and details of successful studies in mice were published in Nature Nanotechnology. The technology, called Tissue Nanotransfection (TNT), sits on the skin and when stimulated, creates tiny pores in the cell membrane of cells, through which reprogramming factors are inserted, converting them into different cells. The method was tested in mice that had badly injured legs with restricted blood flow or necrotic tissue. In the study, skin cells were turned into vascular cells, which formed new blood vessels within a week, rescuing the limb. The study reported a success rate of a whopping 98%.
Human testing is planned for next year and, if successful, could revolutionize the treatment of ischemic injuries. The developers also believe it could be used to treat a range of diseases and conditions, e.g., generating new brain tissue in Alzheimer’s, or stimulating white fat cells to turn into brown fat cells to help combat obesity.
Diabetes medicines may stall Parkinson’s Disease
Parkinson’s Disease (PD) is a progressive disorder which results in death of certain brain nerve cells and reduced production of the neurotransmitter dopamine, causing tremors and movement issues. The cause is unknown and there is no cure, with current treatments aiming to treat symptoms by replenishing dopamine. Now, a new study published in The Lancet has found that a diabetes medicine (Exenatide) improved symptoms in PD patients after 60 weeks of treatment, whereas those in the placebo group experienced a decline in line with normal disease progression. Brain scans also showed less degeneration in the drug-treated group. This suggests the treatment may be targeting the underlying cause of the disease and not just the symptoms.
This was a relatively small Phase II study, but is extremely promising and, as the drug is already approved and widely used, concerns about safety are reduced. The study may also help us understand the cause of PD, as well as provide new treatment options that directly target it.
Staying the course: Antibiotic guidance questioned
It has long been recommended that a patient should take a full course of prescribed antibiotics to fully destroy the harmful bacteria and prevent development of antibiotic resistance. A group of medical professionals has called this guidance into question in a piece in the BMJ. They state that there is no clear evidence that shows not taking a full course leads to resistance and argue that the opposite might be true – taking the drug for too long may increase the chance of resistance occurring. They advise treatment should be taken until the patient feels better, noting, “Antibiotics are a precious and finite natural resource which should be conserved by tailoring treatment duration for individual patients.” They also call for greater patient education to avoid taking unnecessary antibiotics.
Leaders in the field have welcomed the piece in opening the debate and looking for solution to combat the antibiotic resistance threat, however have cautioned against unclear messaging for patients and that further work is required to investigate what optimum treatment length may be. Until then, they advise following doctors’ orders.
Audit shows long way to go for clinical trial transparency
Ben Goldacre continued his campaign for clinical trial transparency with a study published in the BMJ assessing the policies of 42 major pharmaceutical companies on transparency in reporting trials and adherence to ethical and legal guidelines. The audit found that policies were highly variable and often ambiguous, e.g., commitment to publishing data without a given timeframe. Within the article, GlaxoSmithKline was praised for its commitment to share clinical study reports (CSRs) for all trials back to 2000, setting up a company unit dedicated to that. In contrast, AbbVie and Intermune were noted to have sued the EMA to prevent disclosure of similar documents.
In the current environment, the call to publish all trials is not surprising. Full accessibility to data would allow researchers to better understand failed results and learn from them, as well as allowing doctors and patients to make more informed treatment decisions. From the results of this study, it looks like pharma still has some way to go.