The Spanish Medicines Agency recently issued the authorization for the hospital use of NC1, the first advanced therapy medicinal product for treating spinal cord injuries. This revolutionary drug, which has already achieved significant improvements in 30 patients with incomplete spinal cord injuries, was developed by a medical team at the Puerta de Hierro University Hospital in Madrid. NC1 is the result of 25 years of research in a project led by Dr. Jesús Vaquero, who has been able to rely on financing and institutional support from Fundación MAPFRE.

“When the guy in the white coat arrives and says you’ll never walk again, your whole world falls apart. Your life changes in a flash.” This is how Andrés Herrera starkly puts it. Twelve years ago he suffered a spinal cord injury (SCI) in a traffic accident that was to confine him to a wheelchair for the rest of his life. He was just 27. That was until, in 2011, a ray of hope burst through for Andrés and a group of patients in the same situation. A medical team at Puerta de Hierro University Hospital in Madrid, headed by the neurosurgeon Jesús Vaquero, offered them the possibility of participating in a research project based on the use of stem cells for the treatment and regeneration of spinal cord injuries.

The result of this project is NC1, the first advanced therapy drug for the treatment of traumatic spinal cord injuries. The drug has already received authorization from the AEMPS (Spanish Medicines Agency) for hospital use, following 25 years of painstaking research work in which numerous teams of professionals at the Puerta de Hierro hospital participated. A lengthy process that has passed through various stages, from the early in vitro studies, work with stem cells or preclinical test on animals until, in 2013, the first clinical trials with human patients began. The Spanish Medicines Agency has granted authorization for 30 patients to be treated over the first year. The doctors at the Puerta de Hierro Hospital trust that this number could be expanded progressively up to one hundred patients each year.

Unprecedented treatment

NC1 is a fully personalized medication exclusively for use in hospitals. Its design is based on the use of autologous stem cells (i.e. the patient’s own cells), since research has shown that they are more effective and applicable to this type of cases. The process begins with the surgical removal of mesenchymal stem cells from the patient. These cells are transferred in an airtight container directly from the operating room to a cell production room (“the white room”), a sterile environment maintaining special conditions that reduce the risk of contamination throughout the work process. They are treated there and subjected to cultivation for several weeks. Once this process is completed, the medication is prepared and administered to the patient in high concentrations, either at the precise location of the spinal cord injury, or in the cerebrospinal fluid. For the patient, this is the start. Subsequently, long rehabilitation sessions await them in order to reactivate the dormant muscles.

Una puerta a la esperanza
para los lesionados

Enhanced quality of life

Clinical trials with NC1 have demonstrated significant improvements in four main aspects of patients’ lives: bowel and bladder control; improvement as regards motor dysfunction and gait disturbances; increased sensitivity; and reduction of neuropathic pain (caused by damage to the nervous system). All these effects have a highly positive impact on the quality of life of SCI patients. “People see us and think ‘poor people, they can’t walk’. But there are other problems related to spinal cord injuries that are not so obvious, yet make our daily lives much more difficult,” Andrés Herrera reminds us.

One of these lesser known aspects is the loss of sphincter control. Incontinence problems are an ever-present issue which also affects patients psychologically. This can even result in some of these people not wanting to go out, or giving up on their social relationships for fear of having an episode in public. “I’ve even had to ask a friend to help clean me up, and that’s really tough,” Herrera recalls. The cell regeneration therapy has managed to achieve nearly 80 percent of the patients experiencing significant improvements in sphincter control. Increased sensitivity is another improvement common to most of the participants in the clinical trials. To a greater or lesser degree, all of them have made progress in this regard. As those responsible for this project remind us, being able to feel the caress of a loved one after years of not being able to means the world to these people.

Caution needed

The appearance of this drug is undoubtedly excellent news for those affected by this pathology and their families. However, the architects of this important medical advance insist that we should not expect miraculous results, nor raise false expectations. The treatment is limited in scope and, moreover, is not applicable to all cases. Only those patients with incomplete spinal cord injuries, due to vertebral damage at the dorsal or lumbar level, are likely to see improvements thanks to this therapy. “With a completely sectioned spinal cord, it cannot work,” Dr. Jesús Vaquero explains. “There must be minimal anatomical preservation of the patient’s spinal cord on which we can place the cells, so that they can proceed to activate certain circuits which were not functioning, despite being anatomically present,” he adds.

Clinical trials with NC1 have demonstrated significant improvements in four main aspects of patients’ lives: bowel and bladder control; improvement as regards motor dysfunction and gait disturbances; increased sensitivity; and reduction of neuropathic pain.

These limitations mean that it is of the utmost importance to carefully select those patients most likely to benefit from this treatment. A multidisciplinary selection committee of health professionals is in charge of analyzing each of the cases one by one, scrupulously applying a protocol of strict medical criteria. “We have to meticulously analyze the type of injury in question. Another fundamental question is to undertake a genetic study of that patient, as there may be some chromosomal disorder in their cells which could later cause problems during the cell expansion process,” warns the head neurosurgeon at Puerta de Hierro.

NC1 is a fully personalized treatment, adapted to suit each type and degree of injury, which has to be administered in a hospital environment under clinical safety and isolation conditions. We therefore cannot speak of a drug which could be industrially produced for the mass market. “When all’s said and done, this is a cell therapy drug,” Dr. Vaquero reminds us and, as such, its success depends on “meticulous care in the cell production process.” Despite all the limitations and difficulties, this progress is nonetheless an extraordinary medical advance in the field of stem cell research and a ray of hope for those afflicted by this pathology. Regarding its efficacy, Dr. Jesús Vaquero stresses that with this therapy “we cannot heal spinal cord injuries, but we can enhance the quality of life of these patients.”

Public-private collaboration

This milestone in medical research has proved possible thanks to the fruitful collaboration between public entities such as the Puerta de Hierro University Hospital or the regional Department of Health in Madrid, and private entities such as Fundación MAPFRE and the Rafael del Pino Foundation, whose support and funding have enabled NC1 to become a reality. “When we committed ourselves firmly to this project in 1997, the goals they pursued sounded like science fiction. Today, this treatment opens a doorway to hope for the thousands of people who suffer from spinal cord injuries, and represents an impressive qualitative leap in the treatment of this type of pathologies,” stresses Ignacio Baeza, vice chairman of FUNDACIÓN MAPFRE.

Fundación MAPFRE participates each year in initiatives which benefit 25 million people all over the world. The prevention of traffic accidents is, of course, one of the fields of action in which it is most active. However, Fundación MAPFRE’s commitment goes far beyond accident prevention and reaches out to those who have fallen victim to an accident. As Ignacio Baeza reminds us, this is demonstrated by their involvement in over one hundred research projects whose objective, like this one, is to “offer accident victims a second chance.”

Doctor Jesús Vaquero
Head of Neurosurgery at Puerta de Hierro University Hospital

“The patients give us life lessons every day”

Jesús Vaquero

What aspect of this project gives you the greatest satisfaction?
Having succeeded in improving the quality of life of patients with spinal cord damage. We have gone from a pessimistic view where there was no possibility of improvement for paraplegic patients to one where many of the neurological sequelae could prove to be reversible, thanks to new cell therapy techniques.

This has taken many years of research. Were there moments of doubt along the way?
Of course, the road has not been easy; but the hurdles have always been overcome thanks to the support of the patients themselves. At all times they have given us a lesson in overcoming their disability and fighting to keep going. They always give us a lesson in life.

What’s the most difficult thing in this kind of project?
The complexity of the animal trials that must be undertaken first before transferring these studies over to humans. Keeping animals with a spinal cord injury for months to see what can be achieved is a necessary phase before trying things with a patient. These animals must be subjected to constant care and rehabilitation treatments that call for sustained efforts on the part of the researchers.

Does this discovery open up new avenues for the treatment of this type of injuries?
I’d say that it confirms the usefulness of cell therapy for secondary impairments associated with spinal cord injuries. This is important, as the best therapeutic options capable of opening up new avenues for optimism are gradually taking shape. However, prudence is essential and we must avoid sensationalist claims. The important thing is that the best options are being discovered.

Andrés Herrera

Andrés Herrera
Patient (39 years old, Madrid)

“I’ll never forget the first day I felt stiffness in my muscles again”

How did you hear about this project?
One of my mother’s friends read about the project in a medical journal and mentioned it to her. We were so interested that we wanted to contact Dr. Vaquero’s team at once. We sent them an email outlining our case and that was the start of everything.

How long did it take for you to notice the first effects of the treatment?
The first changes came really quickly. My injury is partial, so I still had some sensitivity, but what I didn’t feel was fatigue. Shortly after receiving the first injection, I noticed something strange: aching muscles! Three months later, when I got the second injection, I felt a sharp blow on the soles of my feet and I told Dr. Vaquero about it. He couldn’t hide his surprise and said: “Already, so soon?”

How has your life changed?
Now I have greater independence from my wheelchair. I’m still very active and, although obviously there are situations in which I lack good balance and still need the chair, in general I can cope really well with the help of crutches throughout practically the whole day. The world looks very different when you can stand up instead of from a wheelchair.

David Serrano

David Serrano
Patient (Madrid, 46 years old)

“I can do things I couldn’t before”

How did it all begin?
I suffered a traffic accident in 2002. It was a colleague, who was also on the program, who first mentioned this possibility to me. That was back in 2011. Then there were many tests – psychological, strength, stress, etc. – to try to determine whether the treatment could feasibly be applied to my case. Bureaucratic issues delayed the process for a while more, until I finally began the treatment in 2013.

What improvements have you experienced?
Now I have much better balance than prior to the therapy, and I can do things that I previously couldn’t. I’ve even been able to ride a bike! And not an adapted bicycle, but an ordinary bike. However, while the mobility or balance improvements are really positive, they really aren’t the most important thing for me. When all’s said and done, I was already independent in my wheelchair.

What is that most important aspect?
The principal advance is undoubtedly sphincter control. In my case, this was a real ordeal that, moreover, caused me countless medical problems. Things got so bad that I once had six urinary infections in a single year, some of them so severe that I had to go into hospital. That made my kidneys suffer and forced me to constantly take ever stronger antibiotics.

Have your expectations been met?
My clinical trial was one of the first and it went very well. The problem when you have a spinal cord injury is that there are always lots of people raising expectations and promising you things that never happen. But it was never like that with Dr. Vaquero. He was really sincere from the outset. He told me straight out that I wouldn’t be cured, but that he was indeed sure my life would improve. And that was the case. In addition, the way he and his team treated me was outstanding. They were always really attentive.