Next month, Chinese researchers will edit adult human DNA using the revolutionary CRISPR/Cas-9 tool, commonly known as CRISPR, for the first time anywhere in the world.
The researchers will attempt to cut faulty DNA out of the cells of lung cancer patients who have failed to respond to all other conventional treatments.
Chinese scientists have previously used CRISPR on non-viable human embryos, without much luck, but this is the first time any researchers, anywhere in the world, will use the tool to edit DNA in an adult.
If successful, the hope is that it could lead to further CRISPR treatments – CRISPR/Cas-9 allows researchers to effectively cut and paste DNA in cells, and, in animals, it’s already been shown to treat genetic diseases such as Duchenne muscular dystrophy.
The new trial will begin at Sichuan University’s West China Hospital next month, according to Nature, and will involve patients who’ve already gone through chemotherapy and radiation therapy – in other words, are out of options.
There are also concerns that it could lead to the development of ‘designer’ babies – where parents pick and choose certain traits to write into their child’s DNA.
But it’s important to note that the new Chinese study will only edit patients’ immune system T-cells, and not affect gamete cells that could be passed down to offspring.
In other words, the changes made by CRISPR will be limited to the patient involved in the trial – a number that hasn’t been disclosed as yet.
We do know what the process will involve, though.
In the trial, the Chinese scientists will extract T-cells from patients’ blood and delete a gene that produces a protein called PD-1, which stops T-cells from targeting and killing cancer cells, from their DNA.
The team will then multiply these new CRISPR-modified T-cells in the lab, before injecting them back into the patients to flood their immune system.
The hypothesis is that, with PD-1 inhibited, the T-cells will be able to track down and wipe out lung cancer cells naturally.
While CRISPR/Cas-9 is capable of also inserting new DNA into a cell’s genome, in this study, genetic information will only be deleted, not added.
This is a similar process to immunotherapy studies that are already common around the world – researchers take immune cells, genetically modify them, and insert them back into patients. In fact, gene editing has already saved the life of a girl with ‘incurable’ leukaemia.
But what’s different in this case is the use of CRISPR, which is incredibly simple and versatile.
While in the past it’s taken years for scientists to develop the right molecular ‘scissors’ to cut out specific genes, CRISPR simply needs to be programmed and can then work for any part of the genome – no costly development required.
Last month, the US National Institutes of Health (NIH) approved a similar trial in the states – although the American research will also add an extra gene to help combat three types of cancer: melanoma, sarcoma, and myeloma.
The research could begin as early as this year, but if reports are anything to go off, China will be the first to try out this incredibly powerful tool in humans.
Researcher Arturo Tamayo qualified the findings: “Labeling animal protein completely as beneficial is not helpful until more data are available.”
The study, lead by Xinfeng Liu, of the Nanjing University School of Medicine, looked at seven different studies — four conducted in the U.S., two in Japan and one in Sweden — that plotted and analyzed the health of 254,489 participants. The average length of the seven studies was 14 years.
Lui and his colleagues found that six of the seven studies found a correlation between higher protein intake and fewer strokes, although, only three of the six correlations were statistically significant.
As always seems to be the case with meta-analyses — and especially studies concerning diet and nutrition — the findings were heavily qualified.
“As with all meta-analyses, heterogeneity of studies always has a role,” the authors wrote in their study, acknowledging that each study was conducted separately. Furthermore, none of the studies were designed specifically to parse out a relationship between protein intake and instances of stroke.
“Different geographic populations, poor or incomplete description of other diet components, and comorbidities should all be considered,” they added.
The study was published this week in the journal Neurology.
In an accompanying editorial, another researcher further qualified the results.
“The grain study population was small, and … this could have been a factor for the inconsistent result,” said Arturo Tamayo, of the University of Manitoba. “Therefore, labeling animal protein completely as beneficial is not helpful until more data are available.”
In other words, until more definitive results are available, an uptake in animal protein is probably not the best preventative measure for avoiding strokes.
India’s pre-clinical contract research organisations (CROs) like Bioneeds, Advinus Therapeutics, Syngene and Jai Research Foundation are now looking at non-animal tests like the in-vitro analysis and even considering the advanced computer modelling techniques which are far more reliable to deliver human-relevant results in a day, unlike some animal tests that require a few weeks.
With the prohibition of the animal testing by the Union government and the revision of the Drugs and Cosmetics Rules 1945 inserting a new rule after 148-B with 148-C to forbid animal testing for cosmetics, research institutes like the IISc, NCBS and JNCASR point out that globally sophisticated computer models which accurately predict drug reactions, techniques like the 3-dimensional human cell derived skin model, quantitative structure activity relationships (QSARs) help to replace the use of guinea pigs or mice generating accurate allergic response data.
The departments of pharmacology in international universities have preferred the computerised human-patient simulators to indicate the adverse drug reactions. India with its scientific prowess and research capability could easily adopt the same, stated IISc, NCBS and JNCASR.
Bengaluru-based Bioneeds India, an OECD GLP Certified Pre-Clinical CRO, has already adhered to the European Commission’s Scientific Committee on Consumer Safety (SCCS) SCCS/1297/10 issued on 8 December, 2009 which mandates use of validated alternative methods in toxicological testing. These are Local Lymph node assay, NRU Photo toxicity, Bovine Corneal Opacity Study (BCOP), Dermal percutaneous absorption study (rHES), Direct Peptide Reactivity Assay (DPRA) and In vitro dermal irritation study (Epiderm).
“We anticipated this some time back following the EU directives and finally the Indian government has also taken a stand to implement and passing the message to the global regulators that; India is on par with the ‘Be Cruelty-Free Campaign’. Our scientific personnel are armed with the know-how for in-vitro tests and have pioneered in standardizing and implementing the same. In fact, we are one among the premier CROs in the country to comply with global regulatory guidelines of the European Commission’s SCCS which is still in the preliminary stage of implementation in India,” Dr. SN Vinaya Babu, managing director & chief executive officer, Bioneeds India Private Limited, told Pharmabiz.
However, it would have been better if this decision to ban animal studies for cosmetics becomes a global mandate. India, China and South East Asia are seen as hubs by the US and European Union for pre-clinical research. With the revival of the global economy, there would be a number of opportunities for companies in the region. Therefore adherence to SCCS norms are the need of the hour to grab some of the potential business opportunities, said Dr Babu.
WuXi PharmaTech, a leading pharmaceutical, biotechnology, and TaiMed Biologics, a publicly held Taiwanese biotechnology company, announced that the US FDA has approved the first batch of the ibalizumab (TMB-355) drug substance and sterile drug product manufactured at WuXi’s biologics facilities for ongoing treatment of patients under investigator-sponsored IND‘s. This is the first reported FDA approval of a sterile biologics product manufactured in China for use under a US. IND, which marks an important milestone of WuXi’s investment to expedite global development of innovative biologics.
Ibalizumab is a humanized monoclonal antibody and a member of an emerging class of HIV therapies known as viral-entry inhibitors. It is being developed by TaiMed Biologics for the treatment of HIV/AIDS infection.
The drug substance of ibalizumab was manufactured at WuXi’s cell culture manufacturing facility, which recently received an honorable mention facility-of-the-year award by ISPE. The ibalizumab drug product batch approved by the FDA was manufactured at the newly completed state-of-the-art cGMP parenteral manufacturing facility located within the same campus as the cell culture facility at Wuxi city. The automated filling line can accommodate 2-50mL liquid and lyophilized vial products for global clinical trials and product launch.
“We congratulate TaiMed for progressing ibalizumab further in development and bringing this important drug one step closer to approval,” said Dr Ge Li, chairman and chief executive officer of WuXi PharmaTech. “WuXi is proud to serve as a gateway for developing novel biologics in China. Our integrated biologics discovery, development, manufacturing and testing service platform provides our customers with a seamless solution to bring their biologics products to the market globally and in China.”
“TaiMed is pleased with the speed and excellent execution of this project to ensure the success of this important drug. We look forward to the next phase of collaboration with WuXi to successfully bring the drug to marketing approval,” said Dr James Chang, chief executive officer of TaiMed Biologics.
WuXi PharmaTech is a leading pharmaceutical, biotechnology, and medical device R&D services company, with operations in China and the United States. As a research-driven and customer-focused company, WuXi PharmaTech provides a broad and integrated portfolio of laboratory and manufacturing services throughout the drug and medical device R&D process.
TaiMed Biologics, Inc. is a publicly held Taiwanese biotechnology company with the mission to discover, develop and deliver for the global market innovative medicines that help patients prevail over serious infectious diseases.
Qiagen, a world leader in sample and assay technologies, has offered assistance to India for targeted TB screening as the country has a huge burden of latent TB cases, having potential to develop into full-blown TB cases.
“We are working with governments in several countries like China where the authorities showed keen interest. We have already met the senior officials of the Health Ministry and are willing to help the government whichever way possible,” said Dr Masae Kawamura, senior director scientific and medical affairs at Qiagen.
“TB is a silent killer. There are 1.96 million active cases per year. About 40 percent of Indian population has latent TB. About 5-15 per cent of them could develop into active cases. India should go for targeted screening at a massive level, focusing the high risk areas. The question is whether the Government is willing,” she told Pharmabiz, during her recent visit to the country.
Dr Kawamura, a former TB Controller of San Francisco, said the target of the WHO is to reduce the prevalence of TB cases by 50 per cent by 2015. Globally, 2 billion people are having latent TB cases and some countries had gone for universal screening.
“There are advanced tools for screening the latent TB. We are ready to assist the Government in this regard,” she said. A TB clinician for more than 23 years, she was instrumental in making San Francisco to implement interferon gamma release assay (IGRA) as the first jurisdiction in the US.
One out every four TB patients were found to have diabetes. The government should introduce a system to screen all diabetes patients for TB and all TB patients for diabetes if the country wanted to fight TB effectively in the country, pointed out leading diabetologist Dr Anil Kapur, citing diabetes as high risk area for TB.
Pointing out the challenges of massive screening of latent TB in India, DDr Shalabh Malik, head of department of microbiology and clinical pathology at Dr Lal PathLbas, said the high duties on the diagnostic kits and technologies and lack of indigenously-developed tool kits make fight against TB more complex.