Two companies, BRAIN AG and Bayer Schering Pharma AG, have announced a partnership in the sustainable fermentative and energy-efficient production of steroid compounds using optimized microbial production strains; as a starting material, they will use raw materials derived from plants. BRAIN AG is the European leader in white biotechnology while Bayer Schering Pharma is a global top 10 pharmaceutical corporation. Their aim is to achieve a higher yield with reduced energy input through the processing of highly developed micro-organisms called “designer bugs,” and thus lead to the reduction of greenhouse gas emissions.

Improved process

Dr. Simone Kardinahl, head of microbiological production and development in the Bergkamen plant of Bayer Schering Pharma AG, said that the industrial use of the biotechnologically optimized micro-organisms will help improve the process of steroidal intermediates conversion and help save resources. He also stated that the collaboration with BRAIN AG accelerates and supports their company’s own development regarding these activities. Plants, which contain steroidal components, are sustainable and economical sources of pharmaceutical raw materials and intermediates. Today, besides chemical methods, more and more microbial processes are being used as whole cell biocatalyst reactors for further optimization of the steroidal intermediates in plants.

In line with society and ecology

Speaking for Bayer AG, Dr. Wolfgang Plischke commented that the company can only be successful in the long term if their economic action is in line with man’s social interest and the period’s ecological needs. Dr Plischke is responsible for innovation, technology and environment within the managing board of Bayer AG. He further commented that the focus of their research and development activities is the optimization of their production processes to gain better energy efficiency. With the said process made possible by the collaboration, both parties are expecting about a 10 percent reduction of green house gas emissions.

Strategic business cooperation

Dr. Jürgen Eck, CTO of BRAIN AG, stated that technologies of modern molecular biology that is within the field of Systems Biology allows them to take selective action on the genomes of production strains. Genes with limited product yield will be modulated or substituted. Dr. Eck also added that one of the goals that this collaboration wishes to achieve is to enable the use of designer micro-organisms in the efficient production process of steroidal intermediate conversions. “For BRAIN the expansion of the collaboration with the leading industrial partner Bayer Schering Pharma AG is a continuation of the strategic co-operation business with globally successful partners,“ Dr. Eck concluded.

About the companies

BRAIN, short for Biotechnology Research and Information Network, discovers and develops novel bioactive natural compounds and proprietary enzymes for pharmaceutical industries, as well as cosmetics and food industries. The company harnesses nature’s untapped biodiversity to achieve creative solutions. Bayer Schering Pharma is a research-centric pharmaceutical company that was formed by the merger of Bayer and Schering in 2006. Perhaps best known in public for their product line of combined oral contraceptive pills, Bayer is also known in the areas of gynecology, oncology, andrology, diagnostic devices, special therapeutics, and nuclear medicine.

Researchers from the Michigan State University concluded that adolescents particularly males were more prone to changes in behavior when given anabolic androgenic steroids. The research team headed by Kaliris Salas-Ramirez conducted a series of experiments in Cheryl Sisk’s laboratory of the university. Their objective is to compare the effects of administering steroids to adolescent and adult males. The results were published in the Behavioural Brain Research Journal.

Although the study was conducted on male Syrian hamsters, the researchers still believes that the results were significant. They found out that the effects of steroids were more eminent to adolescents rather than in adult hamsters. It causes some changes in their behavioral patterns when on continuous intake of steroids for two weeks as compared to the group given with a placebo. Anabolic Androgenic Steroids are commonly used by professional athletes and bodybuilders to build muscle mass and strength. Previous studies say that continuous use of anabolic steroids may harm the kidneys and may cause other complications. With this study, it was noted that steroids can also alter the behavior of the user when taken for longer period.

In the experiment, the group injected the male Syrian hamsters with either steroids or a placebo everyday for two weeks. 50 percent of the hamsters were given steroid shots during their adolescence which is between 27 to 41 days of age. On the other hand, the remaining group received steroids after becoming an adult which is from 63 to 77 days of age. The behavior of the hamsters were observed at the first two weeks of the experiment and another obervation was made after stopping the steroid injections four weeks later. The criteria used by the researchers include the changes in the mating and aggressiveness patterns of the subjects.

The researchers administered large doses of steroids which is similar to the steroid intake of chronic human users. “An androgenic anabolic steroids or AAS cocktail, in doses comparable to what a heavy or chronic anabolic steroid human user would administer, led to reduced potential for sexual satiety that persisted at least four weeks beyond the exposure to AAS, whether subjects were treated in adolescence or adulthood,” according to the report. They also added that AAS resulted in persistent increases in aggressive behaviors and flank marking, regardless of the age at which exposure to AAS occurred. The report also explained that flank marking is a testosterone-modulated scent marking behavior that communicates dominance status between adult male Syrian hamsters. The result also suggests that the brains of young adults are vulnerable to the effects of steroids and suffers long-term behavioral and physical changes.

The results, according to the researchers, can help authorities address the steroid problem among the youths. The National Institute on Drug Abuse reported that steroid use in teenagers are increasing and the abuse of this drug reach the highest number in 2000. The survey of the institute prompted some states to intensify their steroid testing programs in high schools. Texas and Illinois were some of the states with strict implementation of the steroid testing. However, some states reduced their budget or completely abolished the program due to its effectiveness. Some questions the program if it can really deter steroid use in the youths.

The rising demand for testosterone in the United States becomes a major industry as it recorded more than $800 million last year. The majority of the consumers of male hormone products are older men who suffer from low testosterone level. However, there are also younger people who are using this product which is considered as an anti-aging supplement. Experts were alarmed on the continued use of testosterone by consumers including professional athletes and bodybuilders because of limited studies that will prove its benefits to the users. According to the Institute of Medicine expert panel, the growth in testosterone’s reputation and increased use by men of all ages in the United States has outpaced the scientific evidence.

In order to shed light on the issues on testosterone use, the government has sponsored a $45 million research. The clinical trial which began last month aimed to know whether symptoms of aging like waning energy, limp libido and poor memory were partly due to testosterone deficiency. The research was headed by Peter Snyder, an endocrinologist from University of Pennsylvania. Peter Snyder has been conducting researches on testosterone for decades and is hoping that the study will provide more information on the interconnection of aging, hormones and health. The trial will be running at 12 medical centers nationwide while Pennsylvania will serve as the coordinating center. Men who are 64 years old above will be the subject of the study. They will be recruiting 800 men to participate in the clinical trial which is considered as the largest so far in testosterone study.

According to an article published in Philly.com, one of the issues that are expected to be resolve in the trial is on how to determine the right level of testosterone. Experts still argue on what is generally accepted low testosterone level. McCullough of the Inquirer said that testosterone levels in the blood fluctuate widely depending on the time of day, and measurement methods vary in accuracy. “Men who are obese or have diabetes tend to have depressed levels,” she said. She also cited a study of middle-class Californians found almost half who were older than 50 fell below the generally accepted “low” threshold of 300 ng/dl (nanograms of testosterone per deciliter of blood), suggesting it’s fairly normal. She also added that testosterone declines gradually but not dramatically with age, unlike estrogen, which plummets to a dribble around age 50.

Some are also hoping that the study will answer questions on the risks of using testosterone and if younger and healthier men could benefit from high level of testosterone in their body. According to McCullough, there are previous studies on male hormone which suggest that it can increase the risk of prostrate cancer, may aggravate sleep apnea and may even increase the incidence of strokes in men. Some says that testosterone use can also lead to male breast cancer.

A renowned prostate-cancer surgeon at Johns Hopkins University, Patrick Walsh is also expecting that the findings of the trial would lead to more sensible use. “Right now, hormones are being tinkered with recklessly,” he said. “Men come in to see me who went to another doctor for vague symptoms. Without measuring testosterone or anything else, that doctor put them on ‘androgen replacement therapy.’ They show up on my door two years later with high-grade prostate cancer. Did the testosterone cause it? I don’t know,” Walsh added.

Marcia Stefanick, Obstetrician-gynecologist from Stanford University also supported the study. “We need information on whether it has benefits before we end up with a situation like with menopausal hormones, where we’re telling millions of women” to use a therapy that does more harm than good,” she said.

To minimize the risks involved, the T Trial ensures the safety of those who will participate in the study. Aside from the age requirement, they will only accept men who have testosterone level below 250 ng/dl. Other criteria include men with complaints like trouble with walking, energy, libido, and memory. Men with other health conditions will be excluded from the study to avoid complications resulting from an increase in testosterone intake. The report also said that the trial will be stopped if the results will put the respondents to greater risk and danger during the treatment.

A new product which is considered as a replacement for traditional steroids is being sold online and on the black market based on an article published by Science Daily. This non-steroidal product is used primarily for the treatment of various diseases which include sarcopenia, osteoporosis, benign prostatic hyperplasia (BPH), and cancer cachexia. SARMs or Selective Androgen Receptor Modulators can give the benefits provided by anabolic steroids but with minimal side effects. This is one of the reasons why the product is becoming popular in the sports arena.

However, the major concern of experts is the absence of further studies to verify its effects and benefits. It is currently classified as a therapeutic product for some diseases but no formal studies have been conducted to support its claims. A group of researchers from the German Sport University Cologne in Germany made an analysis on a particular brand of SARM to determine its content and at the same time gather additional information on the product. According to the Science Daily article, the not yet aprroved arylpropionamide-derived SARM is currently marketed as a green tea and face moisturizer. It can be bought online at $100.

The possible misuse of the product also prompted the researchers to conduct the study. They used state-of-the-art mass spectrometric approaches with high resolution/high accuracy (tandem) mass spectrometry. Dr. Mario Thevis, Ph.D. and his colleagues made the analysis using a sample purchased online. “One unit (30 mL) was purchased online and delivered in a box labeled to contain face moisturizer and green tea extract. The sealed bottle did not declare any content and no further documents accompanied package,” Dr. Thevis said. Additional technical information was also shared by the doctor. He explained that LC-MS(/MS) analysis of the solution revealed the presence of S-4 at approximately 150 mg/mL with equal amounts in each container, yielding a total of 4.5 g of the SARM.

The criteria used by the group involve the active ingredient and characterized by the following:
a) its elemental composition (as determined by high resolution/high accuracy mass spectrometry,
b) comparison to synthesized reference material regarding retention time and product ion mass spectrum, and
c) elucidation of its mass spectrometric behavior. Besides the detection of the active ingredient S-4, a significant amount of byproduct was observed.

The result of the study showed some major concern on the product. Dr. Thevis explained that the product with considerable anabolic properties is readily available on the internet without sufficient research on its undesirable effects. “This is especially significant where uncontrolled dosing is applied and drug impurities with unknown effects are present in considerable amounts as observed in the studied material,” he said.

The issue on the possible abuse of therapeutic products was also tackled in the Conference of Parties to the International Convention against Doping in Sport, held last month at the United Nations Educational, Scientific and Cultural Organization’s (UNESCO) headquarters in Paris. In order to get rid of trafficking and illegal supply of prohibited substances in sports, government agencies should adopt new laws and regulations said WADA President John Fahey.

The researchers suggested that sports organizations should implement screening procedures for emerging therapeutic compounds as part of its drug testing policy. The use of SARM as a performance enhancing drug like anabolic steroids is a new elixir for professional athletes. “Our study demonstrates once more that the misuse of therapeutics without clinical approval by athletes cannot be dismissed,” Dr. Thevis added.

On the other hand, a scientific advisor of GTX which manufactures SARM, said that it works similarly to testosterone but in a more targeted way. He said that SARMs are effective by binding to the steroid receptor in only specific tissue, like muscles. “They are not steroid drugs, but they produce the anabolic effect of the steroids,” Evans said. The drug also shows that it can boost lean muscle mass in older people based on clinical trials.

Every time we talk about steroids, some people would always associate it with undesirable effects. It was also given a bad reputation by professional athletes who use it to enhance performance. The types of steroids, anabolic and corticosteroid are both beneficial to us. There are so many medical uses of these drugs which were not known to many people. Some of its health benefits includes treatment of simple skin diseases to chronic ailments like cancer. Jane Brody of NYTimes wrote that steroids can keep a host of autoimmune diseases and allergic reactions from ravaging the body. She said that steroids are the cornerstone of treatment for ailments like rheumatoid arthritis, asthma, ulcerative colitis, temporal arteritis, psoriasis and even bad cases of poison ivy. Just like with other drugs available in the market, long term use of steroids can produce side effects. It is a must for the user to always consult and seek guidance from a medical specialist. People who are using steroids for years may suffer from complication if not properly supervised by a doctor.

In her article, “Steroids’ Miracle Comes With a Caveat“, Brody suggested some tips on how to mitigate the effects of steroids specially when used to treat an illness for a longer period. The different types of administration of steroids have their own advantages and disadvantages to the user. For example, injectable steroids used repeatedly into a muscle or joint can cause weakening and degenerative changes that limit their usefulness in treating chronic athletic or overuse injuries. The dosage also plays a major role in minimizing the effects of steroids. High doses of steroids can result to weight gain, heart diseases and muscle weakness, just to name a few.

Follow Dosing Instructions

Brody stressed that in order to avoid the side effects of steroids, following the dosing instruction is a must. A patient should not use more than what is prescribed by the doctor. It is not recommended to stop the use of steroids abruptly. Gradual reduction of the dosage should be done when the condition of the patient abates. A “stress dose” of steroids can also be given to boost immune response during extreme physical stress, after surgery, an accident or a new serious illness.

Take Immunizations Regularly

If you are using steroids for longer period, ask your doctor on what particular vaccine you should get. Injections for flu and pneumonia can help your body avoid infections. If you are suffering from high fever, productive cough, pain when urinating or large boils on the skin, consult your doctor immediately.

Taking Steroids After Meals

To minimize the side effects to the digestive tract, it is also recommended to take steroids after meals or together with an antacid. If the patient is suffering from steroid-induced insomnia, it is better to take it early in the day. Seek for medical advice if there is a persistent heartburn or black, tarry stools.

Maintain a Healthy Lifestyle

People taking steroids should see to it that they are having a healthy diet. Supplementation of calcium and vitamin D is necessary to reduce the risk of osteoporosis. Exercise regularly and avoid vices. Quit smoking and if possible limit your alcohol intake. To avoid an increase in the blood pressure and edema, stick to a low sodium diet. Processed foods and snacks usually contain high level of salt. A nutritionist can help you identify what food to take like low-fat and low-cholesterol foods. Regular monitoring of your blood pressure and blood sugar is also necessary.

Two large pharmaceutical companies venture into the development of human growth hormone and other biosimilar products. Critical Pharmaceuticals of Europe recently announced that it will develop a nasal spray of human growth hormone (hGH) using its proprietary technology. The company was able to get £1.5m funding from Wellcome Trust. Pharmaceutical companies are interested in investing in HGH development because of its large market. In 2007, the estimated sales of HGH worldwide reached $2.8 billion. HGH is commonly used for the treatment of growth disorders but it is also popular among athletes.

The chief executive officer of Critical Pharma, Lisbeth Illum said in a press release that the market for HGH represented a major opportunity for their company. She said that the project addresses a large unmet medical need and demand for biological products continue to grow which represents 30% of new drugs. She noted that 98% of the products available in the market including HGH are administered through injection which can cause patient compliance. “Current therapies require daily injections and are strongly disliked by patients and their carers. We believe Critical Pharmaceuticals’ CriticalSorb™ technology has the potential to enable the non-invasive delivery of not just human growth hormone but many other biological drugs with at least equivalent efficacy,” she added.

The company’s CriticalSorb™ technology was proven to enable the efficient delivery of biological drugs with exceptional bioavailabilities during preclinical studies. It is also considered as a “GRAS” material which means that it is generally regarded as safe for drugs administered orally or intravenously.

In its press release, the company will be supported by Wellcome Trust in the development of nasal human growth hormone through phase 1 proof of concept study in human volunteers and determine the long term nasal tolerability of CriticalSorb. The head of Business Development Technology Transfer Division of Wellcome, Richard Seabrook, said that technologies for non-injectable administration of complex drugs like human growth hormone are desperately needed. “We are very pleased to be funding this application of CriticalSorb™ which may avoid patient discomfort and improve eventual outcomes for this patient population. We look forward to Critical’s results,” Seabrook added.

Meanwhile, Access Pharma is also expected to release its new drug at the end of this year. The company developed a Vitamin B12 based nanopolymer drug delivery system for the oral administration of large molecules such as insulin, human growth hormone (hGH), and erythropoietin (EPO) in preclinical animal models. This unique delivery mechanism uses the the body’s vitamin B12 absorption system in a Trojan Horse manner. With this method, it has a potential to eliminate the usual procedure of injecting drugs like HGH, insulin and EPO.

Mike Havrilla, writer for biotech industry wrote in his column that Access is also in the process of validating its insulin product before it finally enters into formal licensing negotiations. “A long-acting, basal insulin product (similar to the activity profile of Lantus insulin) is the most advanced in terms of achieving oral bioavailability of about 80-90% after initially achieving results in the 30-40% range, he said. According to the company, there are two bio-pharmaceutical companies currently conducting preclinical studies on their basal insulin product.