A controversial stem cell treatment for stroke is showing promising signs in the early results of a small safety trial. Speaking at an international conference last week, the researchers warn that it is still early days, but so far five of the six patients who have received doses of the stem cells have shown some improvement and there have been no side effects.
The hope is that the treatment, by repairing damaged brain tissue, will one day help stroke patients regain some movement and ability to speak. Even small improvements can make a big difference to a person who has been robbed of the ability to wash, dress and feed themselves.
The PISCES trial (Pilot Investigation of Stem Cells in Stroke) study, which is based in Scotland at the Institute of Neurological Sciences, Southern General Hospital, Greater Glasgow and Clyde NHS Board, is the first in the world to evaluate genetically engineered neural stem cells in people with disabling ischemic stroke.
The researchers presented the interim results at the 10th Annual Meeting of the International Society for Stem Cell Research (ISSR), which took place from 13 to 16 June 2012, in Yokohama, Japan.
The lead investigator of the trial is Professor Keith Muir, SINAPSE Professor of Clinical Imaging, Division of Clinical Neurosciences at the University of Glasgow. He told the press:
“We remain pleased and encouraged by the data emerging from the PISCES study to date.”
The Phase I trial, which started towards the end of 2010, and follows five years of repeated regulatory rebuffs, is testing the safety of ReN001, a genetically engineered neural stem cell line made by UK biotech ReNeuron.
The trial is controversial because the stem cell line originated nearly ten years ago, from the tissue of a 12-week fetus.
ReN001 is a genetically engineered line of adult stem cells that are described as “committed, not pluripotent”. That is they are not capable of turning into any type of cell in the body: they are already part way down the track of becoming neurons or brain cells.
The trial is testing four different doses of ReN001 in 12 patients, all men over the age of 60, with moderate to severe functional neurological impairments resulting from their stroke. So far only 6 patients, on the lower doses, have received the treatment. The other 6 patients will start receiving the higher doses, comprising around 20 million stem cells, in the coming months.
At the conference, the researchers reported the interim results on 5 of the 6 patients.
They said so far, no adverse side effects, neither from the stem cells nor from the immune system, have been reported. Some patients have experienced minor problems such as superficial scalp infection or minor bleeding where the stem cells were implanted.
Although the main aim of the trial is to evaluate the safety and tolerability of the ReN001 treatment, to help with the design of future clinical studies, the patients are also undergoing tests of movement and brain function that will show if there are any reductions in their disability.
One test, National Institutes of Health Stroke Scale (NIHSS), measures things like speech, eye movement, ability to move arms and legs, and sensation in limbs and face. A high NIHSS score means more disability. The researchers said the pre-treatment median score for the first 5 patients was 8 (ranging from 6 to 10), and at the three-month follow up, it was 4 (ranging from 3 to 9).
Brain imaging data from fMRI scans taken before and after treatment also show some changes consistent with these improvements.
“The data indicate that the ReN001 treatment has a good safety profile at the doses administered thus far. The preliminary signals of potential functional benefit, whilst intriguing, will require further investigation in a suitably designed Phase II efficacy study. The clinical team looks forward to dosing patients in the remaining higher dose cohorts in the PISCES study over the coming months.”
Michael Hunt, Chief Executive Officer of ReNeuron, said we must be very cautious about interpreting these early results, because the aim of the study is to test the safety of the treatment.
“That said, we remain encouraged by the results seen in the study to date and we look forward to providing further updates on the study as the higher dose cohorts are treated and to progressing our planning for further clinical trials with ReN001,” he added.
Should the early promise bear out, and subject to receiving the go-ahead from the Data Safety Monitoring Board, the company hope to apply for a Phase II clinical study (to test the effectiveness of the treatment) during 2013.
Stroke is the third largest cause of death and the single largest cause of disability in adults in the developed world.
Written by Catharine Paddock PhD