Biomarkers of anti-aging gene therapy
In April 2016, BioViva USA published a press release stating that the company's CEO Elizabeth Parrish had undergone an experimental two-component gene therapy intervention, the purpose of which is to rejuvenate the body by increasing the length of telomeres. One of the components of therapy is the myostatin inhibitor gene, which prevents age–related decrease in muscle mass, and the second is the telomerase inducer gene, which counteracts the extinction of the stem cell population, leading to the development of various age-related diseases and disorders. The aim of the experiment was to obtain primary clinical data on the safety of telomerase activity induction, however, a study conducted by SpectraCell Laboratories showed that the length of Parrish leukocyte telomeres increased from 6.71 kb to 7.33 kb, which corresponds to the rejuvenation of the body for about 20 years.
A new, more detailed study of the results of Parrish's examination before and after therapy revealed other positive changes. Comparison of images obtained by magnetic resonance imaging (MRI) shows a slight increase in the volume of muscle tissue with a simultaneous noticeable decrease in the amount of intramuscular fat. Excessive accumulation of intramuscular fat, also known as "marbling", is associated with increased tissue resistance to insulin. Therefore, a decrease in the amount of such fat deposits may be a reflection of positive metabolic changes accompanying an improvement in the condition of muscle tissue. At the same time, the patient's body weight did not change during the observation period, so a decrease in body weight in this case is not a distorting factor. More importantly, the obvious increase in muscle mass occurred without following any training regime. Therefore, experts believe that in more physically active patients, therapy can lead to significantly more impressive results. It should also be noted that the observed growth of muscle tissue is comparable to the improvements observed in patients with Becker muscular dystrophy who received therapy consisting in the introduction of the myostatin inhibitor gene.
Figure 1. Images of Parrish's thighs obtained by magnetic resonance imaging. On the left image – before therapy, on the right – after therapy. In the right image, you can see an increase in total muscle mass, accompanied by a visible decrease in the amount of intramuscular triglycerides (fat).
In 2013, Bernardes de Jesus and co-authors in experiments on mice found that the introduction of the telomerase inducer gene using the adenovirus vector provides a significant reduction in fasting blood glucose levels. Similarly, in Parrish's case, fasting blood glucose decreased from 9.4-8.6 mg/ml before therapy to 7.1-mg/ml in August 2016 (11 months after therapy). Repeated blood tests are necessary to confirm the expected increase in tissue sensitivity to insulin. Earlier studies have also demonstrated that telomerase deficiency disrupts glucose metabolism and insulin secretion in mice lacking this enzyme, which may explain the apparent improvement in metabolic markers.
Figure 2. Fasting blood glucose decreased, which indicates an increase in tissue sensitivity to insulin.
In accordance with the improvement of metabolic health, there was also a decrease in the concentration of triglycerides in the blood from 14 mg/ml in 2015 to 3.6 mg/ml in February 2016 (5 months after therapy), followed by an increase to 8-8.4 mg/ml in August 2016 (11 months after therapy). Despite the fact that the triglyceride level has increased slightly over the past six months, it is still lower than it was before therapy. Both the decrease in fasting blood glucose concentration and the decrease in triglyceride levels can be explained using the results of earlier studies on telomerase and myostatin. The increase in the concentration of myostatin-coding mRNA observed in patients with type 2 diabetes mellitus is associated with impaired tissue sensitivity to insulin, increased triglyceride levels and the development of mild chronic inflammation. In addition, it has been demonstrated that inhibition of myostatin in mice reduces triglyceride levels and improves tissue sensitivity to insulin.
Figure 3. The image shows a pronounced tendency to decrease the concentration of triglycerides in the blood, indicating an improvement in the state of the cardiovascular system.
In addition to the obvious improvements listed above, the results of the blood test allowed us to delve even deeper into the effects of combination therapy. So, a few months after the therapy, a significant decrease was recorded (from 0.16 mg/ml to less than 0.02 mg/ml) in the blood content of C-reactive protein, which is a strong marker of systemic inflammation. This can be explained by the elongation of telomeres that have reached a critically short length, which prevented the cells from entering the phase of physiological aging, in addition to the expected effect of therapy, which is to prevent oxidative damage to nuclear DNA.
Figure 4. The level of C-reactive protein decreased significantly after therapy, which indicates a decrease in the severity of the inflammatory status.
At the same time, the therapy did not cause any negative manifestations. The results of the blood test indicate that it has not had any adverse effect on the body, at least at the moment. This is a conditional confirmation of the safety of the two-component gene therapy strategy developed by BioViva.
According to Elizabeth Parrish herself, the data obtained primarily indicate that such therapeutic approaches are likely safe for humans, the proof of which was the primary task of the study. In addition, they demonstrate potentially positive metabolic changes consistent with the results of earlier studies. The identified trends may find further confirmation in the future, as the company's specialists continuously monitor biomarkers of the state of its body. In any case, the results obtained to date are very impressive.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on BioViva USA: Dual Gene Therapy Has Beneficial Effects On Blood Biomarkers And Muscle Composition.
05.12.2016