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Competitive athletes are always looking for an extra edge that can help them improve performance. According to a new study by Concordia researchers published in the journal Physical Activity and Nutrition, they can find one in the common cranberry.

In a series of trials involving trained distance runners, the researchers found that ingesting a cranberry supplement for 28 consecutive days led to noticeable improvements in both performance and muscle fatigue following 1,500-metre time trials. Reoxygenation rates were faster and running speeds improved by 1.5 per cent.

“When it comes to elite athletes, any advantage can make the difference between finishing fifth or on the podium,” says Andreas Bergdahl, an associate professor in the Department of Health, Kinesiology and Applied Physiology and the paper’s senior author.

Effects of different energy systems

The researchers recruited 14 high-level runners from Concordia’s varsity track and field team and from two Montreal running clubs, who are performing at least five hours of endurance training a week.

The athletes ran two time trials over three separate visits, one a 1,500-metre, the other a 400-metre. The first visit was used as a baseline. At the second, they were given a single large dose of cranberry extract two hours before running. The athletes were then instructed to consume a small dose of cranberry extract daily for 28 days, after which they repeated the runs for a third time.

“We selected these distances to test the effects the cranberry extract had on different energy systems,” says Francis Parenteau, a PhD candidate and the paper’s lead author. “The 400-metre is shorter and of higher intensity and involves the anaerobic system. The 1,500-metre uses the aerobic system but is shorter than what the athletes usually run. Since they do not train to run that distance, we were able to isolate training effects as a variable.”

Besides their running time, the researchers measured their post-exercise blood lactate, a marker for potential muscle fatigue and lack of oxygen. They also attached a portable near-infrared spectroscopy device to the runners to measure muscle oxygenation levels before, during and after their runs.

Following data analysis, the researchers found that 28 days of cranberry extract consumption demonstrated a trend toward increased speed in the 1,500-metre time trial but not in the 400-metre. However, they did notice that lactate buildup was reduced following the 400-metre but not the 1,500-metre compared to baseline.

The data also indicated that the cranberry extract promoted better oxygen extraction by the muscle, improved lactate clearance and slower muscle deoxygenation.

A runner’s best friend, made in Quebec

Cranberries are extraordinarily rich in polyphenols, a natural compound with antioxidant properties. These characteristics help protect the body from the harmful effects of free radical molecules produced by strenuous exercise.

Cranberries are also indigenous to and a major industrial crop for Quebec. The province produces roughly 60 per cent of Canada’s cranberry yield, according to Statistics Canada.

“The beauty of this is that it is all natural,” says Bergdahl. “It is an ergogenic aid, meaning that it is performance-enhancing, but it is not an anabolic steroid. Athletes can get this important boost in their performance just by consuming more cranberries.”

Reference:

Parenteau F, Puglia VF, Roberts M, Comtois AS, Bergdahl A. Cranberry supplementation improves physiological markers of performance in trained runners. Phys Act Nutr. 2023 Dec;27(4):8-14. doi: 10.20463/pan.2023.0032. 

Recently, there has been increasing interest in alternative remedies to support weight management, and one such remedy that has gained popularity is apple cider vinegar.

A recent study conducted in Lebanon aimed to investigate the potential benefits of ACV consumption on weight reduction and metabolic health parameters. This study was published in the journal of BMJ Nutrition Prevention & Health by Rony A. and colleagues.

An investigational gene therapy for a rare neurodegenerative disease that begins in early childhood, known as giant axonal neuropathy (GAN), was well tolerated and showed signs of therapeutic benefit in a clinical trial led by the National Institutes of Health (NIH). Currently, there is no treatment for GAN and the disease is usually fatal by 30 years of age. Fourteen children with GAN, ages 6 to 14 years, were treated with gene transfer therapy at the NIH Clinical Center and then followed for about six years to assess safety. Results of the early-stage clinical trial appear in the New England Journal of Medicine.

The gene therapy uses a modified virus to deliver functional copies of the defective GAN gene to nerve cells in the body. It is the first time a gene therapy has been administered directly into the spinal fluid, allowing it to target the motor and sensory neurons affected in GAN. At some dose levels, the treatment appeared to slow the rate of motor function decline. The findings also suggest regeneration of sensory nerves may be possible in some patients. The trial results are an early indication that the therapy may have favorable safety and tolerability and could help people with the rapidly progressive disease.

“One striking finding in the study was that the sensory nerves, which are affected earliest in GAN, started ‘waking up’ again in some of the patients,” said Carsten G. Bonnemann, M.D., senior author and chief of the Neuromuscular and Neurogenetic Disorders of Childhood Section at the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH. “I think it marks the first time it has been shown that a sensory nerve affected in a genetic degenerative disease can actually be rescued with a gene therapy such as this.”

Participants in this “first-in-human” trial, which began in 2015, received a single dose of the gene therapy, called scAAV9/JeT-GAN, through an injection into the fluid surrounding the spine. The first two patients received the lowest dose of the gene transfer, which was increased in subsequent patients. Four dose levels were tested over the course of the trial, which were estimated based on results from studies in animal models. Only one serious adverse event – a fever – was potentially linked to the gene therapy. The treatment resulted in 129 related adverse events of lesser seriousness, including headache, back pain, irregular heart rhythms, and inflammation in spinal fluid that was treated with corticosteroids. Two patients who were older and received the lowest-dose therapy died during the study period due to events related to their underlying disease.

In addition to safety, Dr. Bonnemann and his colleagues also assessed motor function scores and tests of nerve function among the study participants. With increasing dose levels, they found the probability of any slowing of motor decline was 44%, 92%, 99%, and 90%, respectively. As GAN progresses, electrical measures of sensory nerves decline and eventually disappear. With gene therapy, 6 of 14 patients regained sensory nerve response after treatment—electrical measures increased, stopped declining, or became measurable after being absent.

Mutations to the GAN gene result in an inability to break down intermediate filaments, which are cellular structures that make up the framework of nerve cell extensions called axons. Axons are essential for transmission of signals between brain cells. The disease name refers to the enlarged and bloated appearance of the axon under the microscope. As GAN progresses, the axons of motor and sensory nerves break down, resulting in difficulty with movement and sensation because nerve cells cannot communicate with each other.

The first symptoms of GAN are often a clumsy and unsteady gait, becoming evident as early as 2 or 3 years of age. The disease progresses so that by age 8 or 9, patients typically require the use of a wheelchair, followed by increasingly limited use of the arms and little to no use of their legs. In the later stages, people with GAN often require breathing assistance and a feeding tube.

This trial could also benefit gene therapy for other diseases. Researchers testing other gene therapies have already adopted direct administration into the spinal fluid, which requires lower doses compared to usual delivery into the bloodstream by vein. Injecting into the spinal fluid also reduces the likelihood of an immune response, which enables patients who have developed immunity to adeno-associated virus (AAV), the common virus used as the gene delivery system in the therapy, to potentially receive treatment. Previously, children carrying antibodies to AAV from natural exposure to the virus would have been excluded from gene therapy because of their immune reaction.

Scientists will continue evaluating the scAAV9/JeT-GAN therapy to refine the treatment. Next, investigators plan to test whether the GAN gene transfer is more effective when given to younger children or those in an earlier stage of the disease. The next phase of the trial will help to further determine its safety and efficacy.

Reference:

Bharucha-Goebel, DX, et al., Intrathecal Gene Therapy for Giant Axonal Neuropathy. NEJM. 21 March 2024. DOI: 10.1056/NEJMoa2307952,

USA: Researchers at the University of California San Diego School of Medicine have uncovered a noninvasive approach that can be used to better predict the quality of lab-grown embryos. The new method works by detecting small particles of genetic material, called exRNAs, that are left behind in the liquid media young embryos are grown in. The findings were published on January 10, 2024, in Cell Genomics.

In-vitro-fertilization (IVF), a fertility treatment that involves fertilizing eggs in the laboratory and later implanting them in the uterus, has been a source of hope for many people struggling to conceive. However, the multi-step process is complex, and the overall live birth rate after IVF treatment is only 20-40% in females younger than 40 in the United States. One of the reasons for this low success rate is that it’s very difficult for doctors to determine which lab-grown embryos are most likely to result in a successful pregnancy, so many people seeking IVF must go through multiple rounds of treatment.

“Unfortunately, IVF success still involves a big element of chance, but that’s something we’re hoping our research can change,” said co-senior author H. Irene Su, MD, professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at UC San Diego School of Medicine and a reproductive endocrinologist at UC San Diego Health. “Right now, the best way we have to predict embryo outcome involves looking at embryos and measuring morphological characteristics or taking some cells from the embryo to look at genetic makeup, both of which have limitations.”

Instead of relying on either visual characteristics or biopsies of embryos, the new approach works more like a blood test by detecting molecules in a sample of fluid. However, instead of that sample coming from the embryos themselves, the researchers can analyze embryos by studying the leftover medium used to grow them. This means that the new approach is completely noninvasive and involves no extra steps on the part of the patient.

“IVF is challenging enough as it is, so it was extremely important to us that our research didn’t interfere with this already-delicate process,” said Su. “What we’ve done is more akin to looking at what’s left behind at an archaeological site to help us learn more about who lived there and what they did.”

While DNA contains all the instructions our cells need to develop and function, they also need RNA, another type of genetic material, to help carry out these instructions. Most RNA is found inside of cells, but some RNA molecules, called exRNAs, are released by the cell into their surroundings while the cell completes its various functions.

Scientists are still unsure of the precise biological function of exRNAs, but their discovery in the early 2000s has opened up new avenues in biomedical research and medicine, offering insights into cell-to-cell communication and disease processes, as well as potential diagnostic and therapeutic applications.

“It’s really only in the last decade that we have started to uncover the uses for exRNAs, and there could be countless other applications we haven’t yet discovered,” said co-senior author Sheng Zhong, PhD, professor in the Shu Chien-Gene Lay Department of Bioengineering at UC San Diego. “This is just the beginning.”

By analyzing the exRNA in culture media for embryos at five different developmental stages, the researchers identified about 4,000 different exRNA molecules per stage. These exRNAs correspond to the many different genes that are expressed in embryos at each developmental stage.

“We were surprised by how many exRNAs were produced so early in embryonic development, and how much of that activity we could detect using such a minute sample,” said Zhong. “This is an approach where we can analyze a sample from outside a cell and gain an incredible amount of insight into what’s happening inside it.”

The researchers used the data to train a machine learning model to predict the embryo’s morphology based on the exRNAs it produced. They found that their model was able to replicate the morphological measurements used in current embryo tests, suggesting exRNAs were a promising predictor of embryo quality.

Still, the researchers caution that it will take additional research to confirm whether their test can be used directly to predict positive IVF outcomes, such as successful births.

“We have data connecting healthy morphology to positive IVF outcomes, and now we’ve seen that exRNAs can be used to predict good morphology, but we still need to draw that final line before our test will be ready for primetime,” said Su. “Once that work is done, we hope this will make the overall process of IVF simpler, more efficient, and ultimately less of an ordeal for the families seeking this treatment.”

Reference:

Qiuyang Wu, Zixu Zhou, Zhangming Yan, Megan Connel, Gabriel Garzo, Analisa Yeo, Wei Zhang, H. Irene Su, Sheng Zhong, A temporal extracellular transcriptome atlas of human pre-implantation development, Cell Genomics, https://doi.org/10.1016/j.xgen.2023.100464.

Vitiligo is a chronic autoimmune disease that results from the loss of melanocytes, leading to disfiguring skin lesions. This skin condition causes anxiety and depression, and treatment aims to halt the disease progression, and repigment affected areas. Topical medications and NB-UVB phototherapy are typically used, but in some cases, these treatments may not be effective. Systemic glucocorticoid treatment may help, but these have potential side effects. Other systemic treatments, such as methotrexate, minocycline, ciclosporin, and JAK inhibitors, may also be used as monotherapy or adjunctive therapy.