We have all heard of stem cells. These are the magical ‘starter cells’ that have the capacity to grow into any type of differentiated cell of the adult body. If given optimal growth conditions and with some amount of external hormonal supplementation, theoretically one can induce these multi-potent cells to grow into say liver cells, or brain cells for that matter.

The discovery of this unique potential of these cells led to the probability of using them for therapy. What If these stem cells could be harvested and grown externally in a medium and then transplanted into patients having a chronic dysfunction of cells or organs systems? This would indeed be a much-needed breakthrough in the field of therapeutics. Thus was born the idea of Stem Cell Therapy. The process of injecting stem cells into a person or organism to repair specific tissues or to grow organs is known as Stem Cell Therapy.

Over the years Stem cell research has progressed significantly and the latest news in this field stands testimony to the hard work and relentless research of scientists working in this field. The ReNeuron Group on the second of February, 2010, announced that the UK Gene Therapy Advisory Committee (GTAC) has given a “full and final Favorable Opinion to ReNeuron’s proposed first-in-man clinical trial with its ReN001 stem cell therapy for stroke.”  The GTAC is the national research ethics committee for gene therapy and stem cell therapy clinical trials in the UK. The ReNeuron Company is a Guildford (UK) based stem cell research company. This approval represents the final stage in a long process the company has been going to through to gain approval to test its expanded neural stem cell line on patients suffering from Ischemic stroke. In the official website, the company makes the following declaration:  ‘We have received regulatory and conditional ethical approvals to commence a ground-breaking Phase I clinical trial in the UK with our lead ReN001 stem cell therapy for disabled stroke patients. We are developing stem cell therapies for a number of other conditions, including peripheral arterial disease and diseases of the retina.’

The Re N001 neural Stem cell line has been developed from the brain cells of a fetus (fetal stem cells, which can grow into any one of roughly 210 types of cells in our body) aborted in the year 2003. The fetal stage is the stage attained by an embryo after about 8 weeks of conception in the womb. The company will be able to cultivate all the cells it needs from a single piece of tissue and no more fetal cells will now need to be harvested. These cell lines will now be used to cure patients suffering from stroke, in the very first clinical trial of this sort to ever be undertaken in the field of Stem Cell Therapy in the world. Earlier trials of similar nature have been successful in rodents. Stroke is the third leading cause of death and the single largest cause of adult disability in the world.  Every year, about 5 million people worldwide are disabled by strokes, according to the World Health Organization in Geneva.

ReNeuron won U.K. government approval in January to test its ReN001 stem-cell line after three failures get permission from U.S. regulators. Preliminary

Micheal Hunt-CEO ReNeuron

Micheal Hunt-CEO ReNeuron

analysis of the study next year will determine whether Guildford, England-based ReNeuron can continue developing the treatment and may also determine the viability of the company, whose market value is 19.9 million pounds ($32 million). 1

The company has modified these cells by adding a gene called c-myc to the neural cells. This enables scientists to control the growth of these cells by supplementing the external growth medium with the drug, tamoxifen. What is this c-myc gene? The c-myc gene belongs to the family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein, which is involved in nucleic acid metabolism and further, in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8. 2

The Southern General Hospital in Glasgow, Scotland, will be one of the places where the first of 12 men awaiting the clinical trial will undergo treatment to transplant from 2 million to 20 million neural cells for the purpose of cure from stroke. While there are definitely risks that the company may fail these trials, the approval is a huge step forward in terms of development of this technology. Currently, ReNeuron will enroll only men in ReN001 stem cell line trial because the drug needed to activate or inactivate the c-myc gene which could pose risks for certain women. However, women patients could be added to the trial protocol later on after certain data are confirmed.

A word of caution though, “The facts are it certainly may fail,” said Michael D. West, who founded Geron Corp., the first company to use human embryonic stem cells after they were discovered in 1996, and now is chief executive officer of BioTime Inc., a biotechnology company in Alameda, California. “The risks of this and other cell-based therapies are currently unknown.”

Dr. Keith Muir

Dr. Keith Muir

When the trials begin, Keith Muir, a neurologist at the University of Glasgow, will recruit patients, a process Muir said will take at least two months. No more than one patient can be treated in a month, he said. Complications such as bleeding or injury to the brain are Muir’s biggest concern, he said. Introducing foreign cells into a patient’s body also could lead to immune rejection or swelling. Muir said those risks didn’t appear in rodents or in Parkinson’s disease patients who have undergone fetal brain tissue transplants. “We’ve had a long discussion with people who are experts in immunology and transplant rejection and it seems highly improbable that there’s going to be any clinically important reaction,” Muir said. Another potential risk is cancer. Stem cells may work because they are capable of multiplying, much as cancer cells do. The key to their use is controlling their growth, a process that researchers don’t understand completely.

Michael Hunt, Chief Executive Officer of ReNeuron, said: “This regulatory approval marks the first step in the process of testing the safety and potency of our lead ReN001 stroke therapy at a clinical level. It is the most important milestone in ReNeuron’s history thus far and also represents a significant development in the wider field as regards the translation of exciting stem cell science into clinical stage therapies. In many ways, ReNeuron has set the regulatory pathway in the UK for cell therapy trials of this type, and we are delighted to have been given the opportunity to move ReN001 into its clinical phase on home territory in the UK.”

ReNeuron Patented Technology

ReNeuron Patented Technology

If ReNeuron succeeds in the trial, bigger drug makers may show interest. In the past year, Pfizer Inc., based in New York, said it would invest $100 million in the field over five years and GlaxoSmithKline Plc, based in London, said it would fund $25 million of research at the Harvard Stem Cell Institute in Cambridge, Massachusetts.

Well, the company has spent 3 years in trying to get approval for this promising trial, and has cut down on its research on retinitis pigmentosa, Parkinson’s Disease and Diabetes to save money for the trials. It has undergone a downsizing of staff from 45 to 15 and cut R and D spending by 29 % since last year.

It will be interesting to see where this landmark trial leads us and of course the success of such a brave effort is to be fervently wished for. All the very best to the Scientists as well as the 12 men who will undergo this treatment for the first time in History! !

References:

1 http://www.businessweek.com/news/2009-12-23/injecting-cells-into-brains-means-test-for-reneuron-investors.html

2 http://www.online-medical-dictionary.org/c-myc+Gene.asp?q=c-myc+Gene

3 http://www.reneuron.com/news__events/news/document_228_237.php

4 http://www.reneuron.com/


Image Credits:

1. http://images.google.co.in/imgres?imgurl=http://www.terrapinn.com (Michael Hunt)

2. hdlighthouse.org/…/updates/1338stem_cells.php (Image of the Patented Technology which has been reproduced with permission in the original site; I have merely quoted the site)

3. www.gla.ac.uk/…/news/headline_106255_en.html (Dr.Muir)