Interesting video about GMOs, especially the bit about sweet potatoes. Too bad they didn’t cover “good” GMOs, those with improved overall values such as nutritional, medicinal, etc. GMOs that are not profit driven. Like the one I developed 😁. A transgenic medicinal plant having enhanced defense against plant pathogens and enhanced medicinal effect upon consumption, i.e. beneficial to the environment, to wildlife and farm animals and of course to humans. You can read more about it in the patent application by clicking here.
Hello Dearest Readers,
I am writing few more posts because I would like to share with you some additional informations that will be useful to you. First, my latest research article got published in a top tier biotechnology journal and is open access. You can find a link to it in the menu. It got more than 6000 accesses in less than 5 months and is in the top 17% of most accessed articles of the same source and age. So a big thank you to you all! It took a lot of efforts and faith to get there as I am an independent researcher working with very dependent researchers and very uptight entities called government regulating bodies!
if you have questions about the article, do not hesitate to contact me as it describes an efficient and affordable way to produce a broad range antiviral fusion protein that was found to be particularly potent against chronic hepatitis b virus infections among others.
if you have questions about the nature of my theosophical doctorate in molecular biology and biotechnology, then, you are free to ask away but I won’t answer unless you can tell me first how the below sigil was constructed:
Feel free to wear it any way you see fit (on phones, T-shirts, etc), it will augment the impact of your good deeds by tenfold, for believers. It is monotheistic and an actual authentic talisman (it sums up my thesis of 6 years!), and is called Star of YA.
I am writing to you in order to explain a little bit more the purpose of this blog and why it is coming to an end. Everything you can access on this site has been produced during the many years I spent studying (either at an University, or directly under renown scholars) in order to perfect my knowledge of the world, acquire a certain degree of wisdom and polish my soul. This blog was created to share with you, the readers, some of the knowledge I acquired along the way with the little reasoning I was able or/and allowed to do on my own. I hope you enjoyed it as much as I enjoyed sharing it with you.
It is important to note that I have done all of this out of my own pocket for the most part and I must say it was very expensive, but well worth it. On this note, I would like to thank all those who supported me during the years, mainly, Family, Friends and Believers (with a particular thank to Believers). This is not the reason however as to why it is coming to an end.
As you have noticed, I just added my latest research paper on biotechnology of medicinal plants and the associated published sequence (that you can access freely). This paper marks the end of my years as a student and the beginning of my career as an erudite scholar, and, as such, this site must come to an end. I will leave it up and running of course, but will no longer contribute anything new to it.
Thank you all for your support!
GERMANTOWN, Md., March 12, 2015 /PRNewswire/ — Neuralstem, Inc. (NYSE MKT: CUR) announced top line data from the Phase II trial of NSI-566 spinal cord-derived neural stem cells under development for the treatment of amyotrophic lateral sclerosis (ALS). The study met primary safety endpoints. The maximum tolerated dose of 16 million transplanted cells and the surgery was well tolerated.
Secondary efficacy endpoints at nine months post-surgery indicate a 47% response rate to the stem cell treatment, as measured by either near-zero slope of decline or positive slope of ALSFRS score in seven out of 15 patients and by either a near-zero decline, or positive strengthening, of grip strength in seven out of 15 patients. Grip strength is an indicator of direct muscle strength of the lower arm. ALSFRS is a standard clinical test used to evaluate the functional status of ALS patients. The average ALSFRS score for responders at 9 months after treatment was 37. Non-responders scored an average of 14. These scores represent 93%, versus 35%, of the baseline score retained, respectively, by the responders versus non-responders at 9 months, which is a statistically significant difference. As measured by an average slope of decline of ALSFRS, responders’ disease progression was -0.007 point per day, while non-responders’ disease progression was -0.1 per day, which was again statistically significant. Lung function as measured by Seated Vital Capacity shows that responder patients remained within 94% of their starting scores, versus 71% for non-responder patients. The trial met its primary safety endpoints. Both the surgery and cells were well-tolerated, with one patient experiencing a surgical serious adverse event.
“In this study, cervical intervention was both safe and well-tolerated with up to 8 million cells in 20 bilateral injections,” said Karl Johe, PhD, Neuralstem Chief Scientific Officer. “The study also demonstrated biological activity of the cells and stabilization of disease progression in a subset of patients. As in the first trial, there were both responders and non-responders within the same cohort, from patients whose general pre-surgical presentation is fairly similar. However, we believe that through the individual muscle group measurements, we may now be able to differentiate the responders from the non-responders.
“Our therapy involves transplanting NSI-566 cells directly into specific segments of the cord where the cells integrate into the host motor neurons. The cells surround, protect and nurture the patient’s remaining motor neurons in those various cord segments. The approximate strength of those remaining motor neuron pools can be measured indirectly through muscle testing of the appropriate areas, such as in the grip strength tests. We believe these types of endpoints, measuring muscle strength, will allow us to effectively predict patients that will respond to treatment, adding a sensitive measure of the therapeutic effects after treatment. Testing this hypothesis will be one of the primary goals of our next trial.” The full data is being compiled into a manuscript for publication.
“We believe the top-line data are encouraging,” said Eva Feldman MD, PhD, Director of the A. Alfred Taubman Medical Research Institute and Director of Research of the ALS Clinic at the University of Michigan Health System, and an unpaid consultant to Neuralstem. “We were able to dose up to 16 million cells in 40 injections, which we believe to be the maximum tolerated dose. As in the first trial, the top-line data show disease stabilization in a subgroup of patients. Perhaps equally as important, we believe the top-line data may support a method of differentiating responders from non-responders, which we believe will support our efforts as we move into the next, larger controlled trial expected to begin this summer.”
“The top-line data look very positive and encouraging. If this proportion of patients doing well after treatment can be corroborated in future therapeutic trials, it will be better than any response seen in any previous ALS trials,” said site principal investigator, Jonathan D. Glass, MD, Director of the Emory ALS Center. “Elucidating which factors define a patient who may have a therapeutic response to the stem cell treatment will be the next key challenge. We are hopeful that a set of predictive algorithms can be established to help pre-select the responders in our future trials.”
“We were very excited to participate as a site in this clinical trial,” said Merit Cudkowicz, MD, Chief of Neurology, Massachusetts General Hospital and Co-Chair of the Northeast ALS Consortium (NEALS). “We are hopeful with respect to the top-line results and we need to move swiftly and safely forward to confirm the responder effect and identify people who might benefit from this treatment approach.”
The open-label, dose-escalating trial treated 15 ambulatory patients, divided into 5 dosing cohorts, at three centers, Emory University Hospital in Atlanta, Georgia, the ALS Clinic at the University of Michigan Health System, in Ann Arbor, Michigan, and Massachusetts General Hospital in Boston, Massachusetts, and under the direction of principal investigator (PI), Eva Feldman, MD, PhD, Director of the A. Alfred Taubman Medical Research Institute and Director of Research of the ALS Clinic at the University of Michigan Health System. Dosing increased from 1 million to 8 million cells in the cervical region of the spinal cord. The final trial cohort also received an additional 8 million cells in the lumbar region of the spinal cord.
The company anticipates commencing a later-stage, multicenter trial of NSI-566 for treatment of ALS in 2015. Neuralstem has received orphan designation by the FDA for NSI-566 in ALS.
Neuralstem’s patented technology enables the production of multiple types of central nervous system stem cells in FDA GMP commercial quantities. These stem cells are under development for the potential treatment of central nervous system diseases and conditions.
Neuralstem’s ability to generate human neural stem cell lines for chemical screening has led to the discovery and patenting of compounds that Neuralstem believes may stimulate the brain’s capacity to generate neurons, potentially reversing pathologies associated with certain central nervous system (CNS) conditions. The company has completed Phase Ia and Ib trials evaluating NSI-189, its first neurogenic small molecule product candidate, for the treatment of major depressive disorder (MDD), and is expecting to initiate a Phase II study for MDD and a Phase Ib study for cognitive deficit in Schizophrenia in 2015.
Neuralstem’s first stem cell product candidate, NSI-566, a spinal cord-derived neural stem cell line, is under development for treatment of amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). The primary endpoints were met in Phase II. In addition to ALS, NSI-566 is also in a Phase I trial in chronic spinal cord injury at UC San Diego School of Medicine. NSI-566 is also in clinical development to treat neurological diseases such as ischemic stroke and acute spinal cord injury.
Neuralstem’s next generation stem cell product, NSI-532.IGF, consists of human cortex-derived neural stem cells that have been engineered to secrete human insulin-like growth factor 1 (IGF-1). In animal data presented at the Congress of Neurological Surgeons 2014 Annual Meeting, the cells rescued spatial learning and memory deficits in an animal model of Alzheimer’s disease.
For more information, please visit http://www.neuralstem.com or connect with us on Twitter, Facebook and LinkedIn
Cautionary Statement Regarding Forward Looking Information:
This news release contains “forward-looking statements” made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements relate to future, not past, events and may often be identified by words such as “expect,” “anticipate,” “intend,” “plan,” “believe,” “seek” or “will.” Forward-looking statements by their nature address matters that are, to different degrees, uncertain. Specific risks and uncertainties that could cause our actual results to differ materially from those expressed in our forward-looking statements include risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstem’s periodic reports, including the annual report on Form 10-K for the year ended December 31, 2013 and Form 10Q, for the period ended September 30, 2014.
I recently discovered Haiku and loved it. It is a very short form of Japanese poetry. A traditional Japanese haiku is a three-line poem with seventeen syllables, written in a 5/7/5 syllable count. Often focusing on images from nature, haiku emphasizes simplicity, intensity, and directness of expression.
I decided to give it a try, it is not easy at all!
Empty shore, full moon
Sharp whistling through the stillness –
Bloody sword unsheathed
In darkness, you shine
Your touch, a deadly embrace –
A samurai’s sword
Scent of fresh meadow
Light in the ahead dark woods –
Fleeing for my life
Light rain, heavy steps
Muddled vision, heightened pain –
I fall to his blade
In this journal article, the authors present to us plant-based vaccines as a real solution to impacting worldwide death rate due to infectious diseases. Infectious diseases directly account for 25% of deaths in the world. Traditional vaccines are expensive to administer from all points of view, let it be from availability, infrastructural, development, and medical personal availability. Furthermore, this high associated cost of vaccine delivery hinders the development of new vaccines for diseases that could be prevented.
The added value of plant-based vaccines is that it is orally administered and thus elicits both mucosal and systemic immunity. Additionally, they avoid the associated high costs, the need for trained medical personnel, reduce the risks of infections associated with syringes utilization and improved safety compared to traditional recombinant vaccine since there is no risk of infections by mammalian pathogens. It was estimated that the cost of plant-produced vaccines might be as much as a thousand times less than traditional vaccine production.
However, plant-based vaccines have still not made it through licensing except for one product, a veterinary injectable vaccine against Newcastle disease virus in poultry made from purified antigen expressed in cultured tobacco cells. This is explained by the low yield of the protein, less than 1% total soluble protein (TSP) in lettuce, tomato, potato, and tobacco. Even with the help of improved techniques in recombinant viral vectors or Agrobacterium mediated transformation, the end product has still a low yield and is unstable (uneven expression across the plant).
Plant-based vaccines are still the subjects of many researches as plant cells are attractive for oral vaccines. Their rigid cell walls protect the antigen through the stomach into the intestines so that they can access the gut-associated lymphoid tissue. Unfortunately, the inedible tobacco plants have proven to be the highest-yielding plant in the land species.
Green microalgae has recently attracted the interest of many industries. It has proven to be a very competent protein production platform even when dealing with complex proteins. It has also showed that it can yield product as high as 10% TSP with a sophisticated cellular folding machinery. It has already been used to produce full-length human antibodies with varying expression rate.
The advantages conferred by those unicellular green algae are many. They have all the qualities of plant systems and numerous unique ones over terrestrial plant as vaccine production manufactory. Indeed, the utilization of algae allows for rapid biomass accumulation and the entirety of the biomass is utilized for target protein production without having to waste energy on supporting tissue that do not produce the target protein or can’t be harvested. The authors also remind us of the importance of the fact that algae are not restricted by season, soil fertility and cross contamination risks. Furthermore, they can easily be grown in enclosed bioreactor for higher yield production, withstand long storage period at room temperature when dried, and can endure the harsh conditions of the stomach such as low pH with low antigen degradation, making them the perfect host to produce edible vaccines.
Algae have been used as vaccine production host in the past with some success. It was discovered that codon optimization was critical for high yield and for the oral administration to be effective, the antigen had to be fused to a known mucosal adjuvant such as the beta subunit of cholera toxin (CTB). During a pre-clinical trial, mice were fed freeze-dried algae for 5 weeks and 80% of them survived a lethal challenge with Staphylococcus aurea that killed all control mice within 48hrs.
The authors summarize all the algae produced vaccine up to this day and enumerate the progresses that have been done on algae research; however, the predominant problem is still the low yield of target gene. It is important to note that all those experiments were done for the most part on the same alga model organism C. reinhardtii, and that we are still in early research phase of algae produced vaccines (less than 11 years). The authors also remind us that the advances made on this model organism can be readily applied to other organisms more suited for mass vaccine production. Furthermore, algae have proved to be having a complex folding machinery for heavily disulfide-bonded proteins and are reliable—keep in mind there is no glycosylation machinery in algal chloroplasts.
There is no doubt in the authors’ minds that algae are the right hosts to produced complex vaccine antigens, and that this point was proven repeatedly in the past. For the authors, it is a question of fine-tuning the method. Indeed, even though CTB is the favored adjuvant, fusion of the protein with this adjuvant has been suggested to impair CTB’s activity. This led to many other adjuvants being researched for oral administration. The authors suggest that future work should be directed into finding the proper antigen adjuvant fusion combination as well as optimization the expression levels.
For the authors the future of algae produced vaccine is not to be questioned, but defined and refined. Indeed, given the low associated costs and logistical requirements, the authors go as far as stating that plant or algal production may be the only available option for large scale inexpensive and efficient vaccination. The authors call for investors and the pharmaceutical industry as well to seriously consider this avenue and give it the attention it deserves.
What do you think?
I haven’t written in a long time but needed to share that little piece of news… that is bringing great joy to my heart. I am impatiently waiting for the results… I hope it went well:
U.S.: FDA-approved NSI-566 Phase II trials commenced in September 2013, and concluded final surgeries in July 2014. Phase II concludes after six-month observation period.
Mexico City: NSI-566 Phase I / II trial expected to commence in 2014
Mechanism of Action: Rebuilding neural circuitry
Route of Administration: Direct injections into the spinal cord
Neuralstem is seeking to treat the symptoms of ALS via transplantation of its NSI-566 human spinal cord stem cells (HSSCs) directly into the gray matter of the patient’s spinal cord. In ALS, motor neurons die, leading to paralysis. In preclinical animal work, Neuralstem cells both made synaptic contact with the host motor neurons and expressed neurotrophic growth factors, which are protective of cells. View published papers here: 1, 2, 3.
Neuralstem initiated the first FDA-approved stem cell trial for ALS in January 2010, at Emory University. This Phase I safety trial, to evaluate the safety of the NSI-566 cells and surgical technique, was designed to enroll up to 18 patients. The Principal Investigator is Eva Feldman, MD, PhD, Director of the A. Alfred Taubman Medical Research Institute, Director of Research of the ALS Clinic at the University of Michigan Health System, and President of the American Neurological Association. The Site Investigator is Jonathan Glass, MD, Professor of Neurology, Emory School of Medicine and Director of the Emory ALS Center. The trial was awarded an Orphan Drug Designation by the FDA in February 2011.
In humans, Neuralstem expects that the transplanted cells will:
GRAFT permanently into the region where they were transplanted
REBUILD circuitry with the patient motor neurons
PROTECT patient neurons from further ravages of the disease
In a review of the safety data from the initial nine patients, Neuralstem cells were deemed to be safe, with no adverse reactions reported believed to be related to cells or surgical technique.
Neuralstem ALS Trials
Neuralstem concluded final surgeries in the company’s NSI-566/ALS Phase II trials in July 2014. This phase of the study will conclude after a six-month observation period. The Phase II trials were approved by the FDA to commence in April 2013, upon conclusion of the Phase I FDA-approved trial to test the safety of the neural stem cells and transplantation surgery in patients with ALS in February 2013. The National Institutes of Health and ALSA committed to generous grants in funding for the Phase II phase of the study.
The NSI-566/ALS Phase II dose escalation and safety trials commenced in September 2013, and expanded to three centers: Emory University Hospital in Atlanta, Georgia, site of Phase I; ALS Clinic at the University of Michigan Health System, in Ann Arbor, Michigan, and Massachusetts General Hospital in Boston. The trials were designed to treat up to 15 patients, in five different dosing cohorts. The final cohort have received a total of 16 million NSI-566 neural stem cells, through 40 surgical injections of 400,000 cells per injection. (Phase I maximum was 15 injections of 100,000 cells each.) All of the patients were ambulatory and resided within close geographic proximity to the research center where they participated. The first 12 patients received injections in the cervical region of the spinal cord only, where the stem cells could help preserve breathing function. The final three patients underwent lumbar transplantation and returned for the cervical treatment during a second surgery.
The Phase I safety trial enrolled 18 patients. The trial began with 12 late- to mid-stage patients who received a series of injections in the L2-L4 lumbar region. The first six patients were all non-ambulatory with permanent paralysis. Of these, the first three patients (Cohort A1) were treated with five unilateral cell injections, while the next three patients (Cohort A2) received ten bilateral injections in the same region. The trial then progressed to patients who were ambulatory. The first three of these (Cohort B) received five unilateral injections. The next three patients (Cohort C) received ten bilateral injections in the same lumbar region.
Neuralstem received approval from the FDA to move into the cervical (upper back) stage of the trial in the fall of 2011. The first of six patients in the cervical cohorts to receive stem cells was treated on November 18, 2011, which marked the first FDA-approved intraspinal surgical transplantation of stem cells into the cervical region. The trial then advanced to the final cervical cohort of three patients. The FDA approved the return of three patients from earlier cohorts to receive cervical transplants, making them the first to receive stem cell transplantation in both the lower and upper parts of their spinal cord. The first of these was treated in June 2012, and received five stem cell injections into the cervical region of the back, for a total of 15 injections, including the ten lower-back injections previously received. The last patient in the Phase I trial was treated in August 2012. The trial was designed as a safety trial to treat 18 patients, and concluded six months after the final surgery.