promising results with cell therapy

Seattle, USA — In patients with traumatic brain injury (TCI), injections of stem cells into the injured area of ​​the brain allowed recovery of motor function, without notable adverse effects, according to a US phase 2 study, the results of which have been reported. presented at the annual meeting of the American Academy of Neurology (AAN 2022) ^[1]. The patients had brain damage for an average of eight years.

The effect on motor function was observed one to two weeks after treatment. During the six-month follow-up, the patients improved their walking and some were able to recover the use of their arms and hands. A teenager also regained speech, while he was totally aphasic after his trauma.

“For the first time, we have been able to demonstrate that it is possible, using stem cells, to influence the clinical results of patients with CTCL and presenting with moderate to severe disability”, commented the author. principal of the study, the Pr Peter McAllister (Yale University School of Medicine, New Haven, USA), with Medscape International Edition.

“I think the potential for regenerative medicine has always been there, but now we have reached a sufficient level to bring it to fruition,” added the researcher, also co-founder of the New England Institute for Clinical Research (Stamford, USA). United).

MRI-guided operation

Occurring after a violent shock, traumatic brain lesions lead to a more or less significant disturbance of cognitive and motor function, associated with mild symptoms (post-traumatic headaches, mood disorder, cognitive impairment, etc.) to severe (coma, amnesia after injury…). They can induce motor deficit and chronic physical handicap.

In the absence of effective treatment, researchers are increasingly focusing on the potential of somatic stem cells to attempt to restore lost functions. They are thought to help repair and regenerate damaged tissues through their ability to multiply and differentiate into specific cells.

In this study, Prof. McAllister and his colleagues included 61 patients with lesions after head trauma (70% men), with an average age of 34 years. The brain lesions had been present for an average of eight years and, when they occurred, they were associated with a Glasgow Functionality Score (GOS-E) ranging from 3 (severe disability with complete dependence) to 6 (moderate disability with possible return to work).

A total of 46 participants received stem cell therapy at varying doses (2.5 x 10⁶5 x 10⁶10 x 10⁶ stem cells) and 15 had a sham procedure (sham). The experimental regenerative medicine treatment, called SB623, was developed by the company SanBio. It is made up of mesenchymal stem cells extracted from the bone marrow of a male donor.

Improvement in one to two weeks

Lasting about 20 minutes, the operation carried out by the neurosurgeon consists of injecting the stem cells directly into the area of ​​the brain lesion using a needle guided by MRI and introduced through a small hole made in the skull.

In the case of the sham procedure, the participants were brought into the operating room, anesthetized and the hole was also made over the area of ​​the lesion, but the surgeon stopped after drilling half of the hole. thickness of the skull.

During the first six months of the study, the volunteers were asked to perform specific morning and afternoon physiotherapy exercises at home each day as part of a motor function rehabilitation programme.

The primary endpoint relates to changes in the Fugl-Meyer motor score (FMMS). This score is widely used in the clinical evaluation of motor function to measure in particular the amplitude of movements, the quality of walking, the mobility of the lower limbs, as well as dexterity.

At 24 weeks, the increase in the FMMS score in patients treated with stem cells was greater than that observed in the control group (average increase of 8.3 against 2.3 points according to the least squares method).

“Analyzing all the data at six months, we see that the patients who received the stem cells had better results, compared to the group of the sham procedure”, and the progress began to be observed from the first or second week, says Professor McAllister.

The use of the hands regained

The treatment had a real impact on patients’ lives, the researcher added. For example, “some were able to brush their teeth or put a nut on a bolt, which they were unable to do before”, since they could no longer move their arms. A totally aphasic teenager was also able to utter a whole sentence.

Interestingly, the average dose at 5X 10⁶ has “by far” given the best results. However, Professor McAllister points out that it is not yet known whether these improvements are permanent or not.

Regarding the secondary endpoints, the treated patients also had better results, both on specific changes in limb function – measured by the ARAT (Action Research Arm Test) score – and on the speed of walking on ten meters (Gait speed score) or quality of life with neurological disorders (Neuro-QOL score).

However, even if the differences observed with these secondary endpoints are clear, they are not statistically significant, probably due to the small size of the study and the fact that improvements were also noted in the control group, underlined the specialist.

The mechanism by which cell therapy works is still not well understood, he adds, but researchers believe that stem cells may also have anti-inflammatory properties, helping to create a beneficial environment for multiplication and growth of nerve cells.

A planned phase 3 study

At 48 weeks, at least one side effect was reported by the patients, both in the group testing the therapy and in the control group. But, “no worrying sign was observed with the stem cell treatment”, indicated the researcher, who announced the launch of a phase 3 study with this experimental therapy.

This approach could prove useful for treating other disorders. According to Prof. McAllister, a study evaluating cell therapy in stroke patients “nearly missed significance”, probably due to the methodology used and a patient population that was too old and too sick. The company announced the launch of another study in the treatment of stroke.

The use of stem cells is also being considered in the treatment of cerebral hemorrhage, Parkinson’s disease, multiple sclerosis and other disorders affecting the nervous system.

Asked by Medscape International Editionle Dr Franck Conidi (Florida Center for Headache and Sports Neurology, Palm Beaches, USA) specialist in head trauma, indicated that stem cell therapy is the most promising treatment in the management of brain injuries. “This is the Holy Grail of modern times.”

In this study, “observing a modest improvement in gait as the primary outcome is impressive.” In addition, the study did not report any significant or serious adverse effects, which is “promising”.

This type of study “will help lay the groundwork for future trials and, hopefully, one day lead to a safe non-invasive treatment” to treat head injuries, but also spinal cord injuries, neurodegenerative diseases, like Parkinson’s or Alzheimer’s, or any other disorder affecting the nervous system, Dr. Conidi pointed out.

He says the therapy being tested in this study involves an invasive procedure to implant stem cells into the brain. “At present, it is not possible to bring stem cells through the vascular route and make them cross the blood-brain barrier”.

It should also be checked whether this approach has an effect on cognitive function, which is generally more affected than motor function in the event of brain damage.