ImStem Biotechnology, Inc. (ImStem), a biotech company developing human embryonic stem cell based therapeutic products for tissue regeneration and autoimmune diseases, has successfully treated an animal model of multiple sclerosis (MS) using human embryonic stem cells (hESC) derived mesenchymal stem cells (MSCs), called hES-MSCs.
MS is a chronic neuroinflammatory disease with no cure. Most current MS therapies offer only palliative relief without repairing damaged nerve cells. MSCs may reduce neuroinflammation and promote nerve cell regeneration in MS.
Now researchers from ImStem, in collaboration with University of Connecticut Health Center (UCHC) and Advanced Cell Technology, Inc.(OTCBB: ACTC), have developed a novel therapy to treat MS with hES-MSCs. They found that hES-MSCs are more effective in treating animal model of MS than MSCs from bone marrow of adult human donors (BM-MSC). This work is published in the June 5th 2014 online edition of Stem Cell Reports, the official journal of International Society for Stem Cell Research.
“The beauty of the new hES-MSCs is their consistently high efficacy in MS model. This is a big surprise when we found that most BM-MSC lines show poor or no efficacy. Additionally, BM-MSCs but not hES-MSCs express high level of IL-6, a proinflammatory cytokine can worsen the disease. This definitely adds more advantages to hES-MSCs, which are younger, purer and only express the right factors” says the lead author Dr Xiaofang Wang, CTO of ImStem.
“These great advantages perfectly match the requirements for safety and quality control of clinical-grade MSCs as a potential therapy for autoimmune diseases such as multiple sclerosis, inflammatory bowel disease and rheumatoid arthritis.” says Dr Ren-He Xu, the corresponding author, CSO of ImStem and professor of the University of Macau.
Dr Joel Pachter, a UCHC collaborator, observed fluorescently labeled hES-MSCs but not BM-MSCs effectively penetrated the blood brain barrier and migrated into inflamed spinal cord. He remarks, “This difference is extraordinary as it could hold a key to the therapeutic action(s) of hES-MSCs. MSCs might require access to specific sites within the central nervous system in order to remediate disease.”
“This was unexpected as bone marrow MSCs are widely believed to be effective in this EAE animal model. Our data indicate that the use of BM-MSCs is highly variable and there may be a previously unrecognized risk of poor outcome associated with IL-6 produced by these cells,” says Dr Stephen Crocker, another UCHC collaborator.
Imstem was founded by Dr. Xiaofang Wang and Dr. Ren-He Xu, former director of UConn Stem Cell Core in 2012. In 2013, ImStem was awarded a $1.13M grant from the State of Connecticut Stem Cell Research Program and a $150,000 pre-seed fund from Connecticut Innovations. With these supports, ImStem has improved the hES-MSC technology with better efficiency and safety and has developed clinical grade hES-MSCs in its cGMP facility. ImStem is now seeking approval for phase I clinical trials using its hES-MSCs and is looking for investors to fasten the progress. “ImStem, our first spinoff company from the UConn Stem Cell Core, is uncovering the translational potential of hES-MSCs. ImStem’s cutting-edge work demonstrates the success of Connecticut’s Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside.” says Dr Marc Lalande, director of the University of Connecticut Stem Cell Institute.
“Connecticut’s investment in stem cells, especially human embryonic stem cells, continues to position our state as a leader in biomedical research,” said Governor Dannel P Malloy. “This new study move us one step closer to a stem cell based clinical product which could improve people’s lives.”
The high power committee (HPC), headed by Prof. P N Tandon, has recommended to the Indian Council of Medical Research (ICMR) to discontinue several ongoing activities and programmes of ICMR in 12th Plan.
The committee in its report recommended the discontinuation of exploratory and piecemeal research related to herbal products being undertaken at various centres except where a promising lead has been found. It also noted that RMRC, Belgaum is specialized in this area and can be consulted by others for any lead in plant based research of their interest.
Likewise, the committee has also recommended that research on toxicology, metabolic (diabetes) and chronic diseases may be discontinued at NIOP, New Delhi to avoid unnecessary duplication with other institutes.
The Union health ministry had constituted the committee in December, 2012 to evaluate the ongoing activities of the ICMR with the mandate of whether the ongoing schemes of the XI Plan need to be continued in XII Plan or dissolved forthwith; in case if they are to be continued then the need for improvement; phasing expenditure in XII plan for each component of the scheme; and setting of physical and financial milestones/targets for the XII Plan for each component.
Other activities and programmes of the ICMR which the committee recommended to discontinue included studies on the economic cost of dengue in India; nutrition monitoring survey on NNMB pattern in Jodhpur district of Rajasthan; role of cytokines in chikungunya infection in order to generate information with a view to alter current treatment strategies; studies on chronic arthropathy, a complication in chikungunya infection to assess whether patient management strategies could be altered; electronmicrographic studies related to pathogenesis of leprosy; comparative molecular modeling of various important proteins of different leishmania strains and ligand-protein interaction; identification and characterisation of sperm flagellar proteins relevant to motility, etc.
What is Lupus?
Lupus is a disease that can damage many parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels and brain. It is an autoimmune disease—an illness that occurs when the body mistakenly detects its own tissue as foreign and attacks itself, and can be fatal in some severe cases. While people of all races can have the disease, African American women have a three-times higher number of new cases than white, non-Hispanic women. African American women tend to develop the disease at a younger age than white, non-Hispanic women and to develop more serious and life-threatening complications. It is also more common in women of Hispanic, Asian and Native American descent.
The underlying cause of lupus is not fully known, and there are many types of the disease. The most common form, called systemic lupus erythematosus, commonly causes mouth sores, rash, fatigue, joint pain and swelling, as well as affecting the kidneys.
Lupus also is a chronic disease. “With treatment, the disease may quiet down, but it also may relapse eventually. Although it may be controlled with medications, once you get it, you will always have it,” explains Sarah Yim, M.D., a rheumatologist at the Food and Drug Administration (FDA). A person with lupus will have good periods and bad periods, she says, and symptoms can range from mild or moderate to severe.
Who is Affected?
Estimates vary on the number of lupus sufferers in the United States, ranging from approximately 300,000 to 1.5 million people. According to the American College of Rheumatology, ten times more women than men have lupus, and the disease often starts between the ages of 15 and 44.
What makes lupus so hard to diagnose? A lot of people can be called lupus sufferers but can all have different things wrong with their immune systems, Yim says. And many of the symptoms that can occur in someone with lupus are non-specific and can also occur in other diseases, making it hard to nail down the diagnosis.
Jonca Bull, M.D., director of FDA’s Office of Minority Health, says there is still an enormous need for better therapeutics, and that scientists may be on the cusp of more refined therapies that bring symptoms under control and bring about remission of the diseases that are associated with susceptibility to lupus or play a role in its development. FDA’s Office of Women’s Health has funded several studies related to lupus and other autoimmune diseases in recent years.
Treatment of lupus depends on the part of the body being affected by the disease, and how serious the problem. FDA approved the first drug to treat lupus, aspirin, in 1948 and later approved corticosteroids, such as prednisone, which suppress the immune system and reduce inflammation. In 1955, the agency approved the antimalarial drug Plaquenil (hydroxychloroquine) which helps to relieve some lupus symptoms such as fatigue, rashes, joint pain or mouth sores.
Part of what makes lupus research such a challenge is that the precise problem with the immune system is so different among patients, Yim says. New research is trying to zero in on what the best targets might be.
“Technologies have been developed in recent years that can make our medicines more targeted to address the specific molecule or molecules in the immune system that may be causing the problem,” Yim says. “Older medicines tend to suppress the whole immune system, which works, but it’s a little bit like shooting a fly with a cannonball, and can be associated with many undesirable side effects.”
FDA approved Benlysta—the first targeted therapy for lupus—in 2011. Benlysta is delivered directly into a vein. It is designed to target a protein called B-lymphocyte stimulator, which may reduce the impact of abnormal cells thought to be a factor in the development of lupus.
Yim says that Benlysta doesn’t work for everyone, and not enough research has been done yet to know if it will work in people with very severe lupus. But it works well for lupus patients with skin and joint involvement, she says.
Advances in the understanding and treatment of lupus over the last several decades have resulted in people with the disease living longer.
Despite these advances, however, there remain many people with lupus who need additional treatment options. FDA remains committed to working with researchers and drug developers to help make new treatments a reality.
This article appears on FDA’s Consumer Updates page, which features the latest on all FDA-regulated products.
The union health ministry’s expert panel, constituted for the massive exercise of examining and regularising the thousands of fixed dose combinations (FDCs) permitted for manufacture and sale in the country without due approval from the Drugs Controller General of India (DCGI), will hold its fourth meeting on June 11 to scrutinise several FDC applications filed by different pharma companies.
The expert panel, set up by the CDSCO following the huge number of applications, running over 5000, has already held three meetings and examined several FDC drugs. The experts who will be examining the 15 FDC drugs on June 11 included Dr Renuka Kulkarni Munshi, Dr Iqbal Kaur, Dr Subhash Giri, Dr Niranjan Mohanty and Dr B Gupta.
The panel will assess the efficacy and safety profile and presentations filed by these companies before taking any final decision. After the DCGI asked the industry to prove the efficacy of the FDCs permitted by the SLAs without concurrence of the DCGI, thousands of applications came to the DCGI office. The authorities then set up a committee to work out the modalities on how to examine the applications as there were not guidelines and norms in this regard.
The panel will go through the applications for the FDC products filed by Hetero Labs (azithromycin 125mg/250mg/500mg + cefixime 100mg/200mg/200mg tablets); Valence Healthcare (cefixime (as trihydrate) 200mg +azithromycin drihydrate IP 250mg film coated tablets); Relax Pharmaceuticals (cefixime 200/200mg + azithromycin 250/500mg tablet); East West Pharma (cefixime trihydrate IP 200mg +azithomycin dihydrate IP 500mg film coated tablets); FDC Ltd (cefixime 100mg +azithromycin 125mg dispersible tablets); and Akums Drugs & Pharmaceuticals Ltd (azithromycin 250mw500mg +cefixime 200mg tablets).
The panel will also examine the FDC applications filed by MDC Pharmaceuticals (cefixime IP eg. to anhydrous cefixime 200mg +acetyl cysteine USP 300mg film coated tablets); Akums Drugs & Pharmaceuticals (cefixime IP eg. to anhydrous cefixime 400mg +levofloxacin hemihydrate IP eq. to levofloxacin 500mg tablets); Talent Healthcare (cefpodoximc proetile IP 200mg +azithromycin dihydrale IP 250mg film coated tablets); Macleods Pharmaceuticals (cefpodoxime proxetil 200mg +azithromycin 250mg film coated tablets); Aeon Formulations (cefpodoxime 320mg +azithromycin 500mg tablets, and cefpodoxine 100mg +azithromycin 125mg dispersible tablet); and Orbit Lifesciences (azithromycin dihydrate lP eq. to azithromycin 250mg/500mg +cefpodoxime proxetil IP eq. to cefpodoxime 200mg film coated tablets, and cefpodoxime proxetil 200 mg + dicloxacillin sodium 500 mg tablets).
The list also include Relax Pharmaceuticals (cefpodoxine proxetil 200 mg + levofloxacin hemihydrate 250 mg tablets); Akums Drugs & Phannaceuticals (levofloxacin 250mg/500mg +azithromycin 250mg/500mg tablets);Gelnova Laboratories (anhydrous azithromycin 250mg/500mg +anhydrous levofloxacin 250mg/500mg tablets); Synokem Pharma (azithromycin 250 mg/500 mg + levofloxacin 250 mg/500 mg film coated tablet); Hetero Labs (azithromvcin 250mg/500mg +levofloxacin 250mg/500mg tablets); Arion Healthcare (beclomthasone dipropionate O.025%w/v + clotrimazole l%w/v +chloramphenicol 5%w/v +gentamycin sulphate 0.3%w/v + lignocaine HCI 2%w/v ear drops); Aeon Formulations (ciprofloxacin HCI IP 250mg +phenazopyridine HCI USP 200mg film coated tablets); Alembic Pharmaceuticals (roxithromycin IP 150mg +serratiopeptidase 10mg film coated tablets); Akums Drugs & Pharmaceuticals (sulphadiazine sodium 100 mg + trimethiprim 20 mg oral powder); and Bushal Healthcare (trimethoprim IP 200mg +sulphadiazine IP 1000mg uncoated tablets).
Thousands of FDC drug manufacturers in the country engaged in production of drugs licensed prior to September 21, 1988, can now heave a sigh of relief as the Drugs Controller General of India (DCGI) has excluded such drugs from the requirement of proving the safety and efficacy of FDC drugs licenced by the SLAs without due approval from the DCGI.
On January 15 last year, the DCGI had asked the manufacturers to prove the safety and efficacy of the FDCs approved before October 1, 2012 and had made it clear that those FDCs approved by the State licencing authorities (SLAs) from October without the permission of the DCGI will be considered for ban.
“An issue has been raised regarding applicability of above requirements for FDCs licensed by State licencing authorities before 21.09.1988, after which all relevant provisions relating to New Drugs were introduced in Drugs and Cosmetics Rules. The matter has been considered by this office and it is hereby clarified that requirements of providing safety and efficacy as mentioned above is not applicable for such FDCs which are licensed prior to 21st September 1988”, DCGI Dr GN Singh clarified in a letter addressed to all the state drug controllers in the country.
The DCGI’s clarification comes at a time when the DCGI’s office is conducting the massive exercise of examining the rationality of thousands of FDCs permitted by the SLAs without due approval from the DCGI.
The union health ministry had earlier constituted expert panels for the exercise of examining and regularising the thousands of fixed dose combinations (FDCs) permitted for manufacture and sale in the country without due approval from the DCGI. The expert panels have already held three meetings and the fourth meeting is scheduled for June 11.