BrainStorm Cell Therapeutics Will Conduct Phase 2 Clinical Trial on ALS Patients with Their NurOwn® Cells

The biotechnology company BrainStorm Cell Therapeutics Inc. has developed an autologous stem cell therapy for several neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig’s disease), Multiple Sclerosis (MS) and Parkinson’s Disease (PD). BrainStorm has designed a proprietary product called NurOwn™ that is made from the patient’s own bone marrow mesenchymal stem cells (BM-MSCs). Essentially, the patient’s BM-MSCs are isolated, purified, and cultured in a specialized culture system that drives the BM-MSCs to differentiate into nerve-like cells that Neurotrophic Factors (NTF). These NTFs have the capacity to keep nerve cells alive and prevent moribund cells from dying.

Figure taken from
Figure taken from 

By transplanting NurOwn cells back into the patient at or near the site of neural damage, in the spine and/or muscles, it could potentially delay or even roll back damage from neurodegeneration. NurOwn cells have proven their efficacy in animal experiments (e.g., STEM CELLS 2008;26:2542–2551), and in a few small clinical trials.

In one case, a 75-year-old man who suffered from ALS and myasthenia gravis (the immune system attacks your own receptors for acetylcholine at the neuromuscular junction, which prevents the muscle contraction), was treated with NurOwn cells, and experienced the following improvement 1 month later.

Figure copying (a test of visuospatial function) of the patient, before and 1 month after the first enhanced (neurotrophic factors producing) mesenchymal stem cell (MSC‐NTF) transplantation.
Figure copying (a test of visuospatial function) of the patient, before and 1 month after the first enhanced (neurotrophic factors producing) mesenchymal stem cell (MSC‐NTF) transplantation.

This is only a case study and involves only one patient, which is the absolute lowest-quality evidence you can have in medicine.  Therefore, this study is suggestive that NurOwn cells can help ALS patients improve.

Now BrainStorm Cell Therapeutics has entered into a collaborative agreement with Hadassah Medical Center in Jerusalem, Israel, to conduct a Phase 2 clinical trial to test the ability of NurOwn cells to treatment patients with Amyotrophic Lateral Sclerosis (ALS).

This clinical trial is not BrainStorm’s first rodeo, since they have conducted two other clinical trials in collaboration with Hadassah Medical Center. BrainStorm hopes that the results of this clinical trial will provide guidance in preparing a Phase 3 clinical trial that will test their NurOwn® stem cell based therapy in patients suffering from ALS.

In this trial, BrainStorm plans to enroll up to 24 ALS patients, all of whom will receive three consecutive stem cell transplantations of their own BM-MSCs that have been genetically engineered to secrete NFTs. The goal of this trial is to establish the safety and efficacy of a treatment regimen that includes multiple doses of stem cells. Because this trial includes human subjects, it must be approved by Hadassah’s Helsinki Committee and the Israeli Ministry of Health before the study can commence.

Professor Dimitrios Karussis, MD, PhD, Head of the Unit of Neuroimmunology and Cell Therapies at Hadassah’s Department of Neurology, who served as Principal Investigator in Brainstorm’s prior ALS studies, will serve as the Principal Investigator for this trial.

“NurOwn has generated promising clinical data in ALS and has the potential to offer a new approach for the treatment of patients afflicted with this disease,” stated Professor Karussis. “We are excited to be collaborating with BrainStorm to advance this product to the next phase of development and the application of stem cell therapies in similar neurological diseases in general.”

“Evaluating multiple doses with NurOwn is an important next step in our efforts to understand the treatment effect of this investigative medicine,” stated Chaim Lebovits, CEO of Brainstorm. “We are pleased to continue our partnership with Hadassah Medical Center, which has long maintained a reputation for excellence in the treatment of neurological disorders.”

Umbilical Cord Blood Stem Cells Revive Child From Persistent Vegetative State

Physicians from Ruhr-Universitaet-Bochum (RUB) have successfully treated cerebral palsy in a 2.5-year old boy with his own cord blood.

“Our findings, along with those from a Korean study, dispel the long-held doubts about the effectiveness of the new therapy,” says Dr. Arne Jensen of the Campus Clinic gynaecology. Jensen collaborated with his colleague Prof. Dr. Eckard Hamelmann of the Department of Pediatrics at the Catholic Hospital Bochum (University Clinic of the RUB). This case study was published in the journal Case Reports in Transplantation.

At the end of November 2008, a young child’s heart stopped (cardiac arrest), and his brain suffered oxygen deprivation, and, consequently, severe brain damage. He was in a persistent vegetative state, and his body was completely paralyzed. This condition, infantile cerebral palsy, until now, has no recognized treatment. Typically, the prognosis of children with infantile cerebral palsy is rather grim, since the chances of survival miniscule and months after suffering severe brain damage, the surviving children usually only exhibit minimal signs of consciousness. According to the physicians at RUB, “The prognosis for the little patient was threatening if not hopeless.”

However, this child’s persistent parents scoured the literature for alternative therapies to infantile cerebral palsy. Arne Jensen explains. “They contacted us and asked about the possibilities of using their son’s cord blood, frozen at his birth.”

Nine weeks after suffering brain damage, on 27 January 2009, Jensen and his colleagues administered the child’s prepared cord blood intravenously. They studied the child’s progressive recovery at 2, 5, 12, 24, 30, and 40 months after treatment.

After the cord blood therapy, the patient, however, recovered quickly. Within two months, the child’s spasms decreased significantly. He was able to see, sit, smile, and to speak simple words again. Forty months after treatment, the child was able to eat independently, walk with assistance, and form four-word sentences. “Of course, on the basis of these results, we cannot clearly say what the cause of the recovery is,” Jensen says. “It is, however, very difficult to explain these remarkable effects by purely symptomatic treatment during active rehabilitation.”

Just listen to the description of the child’s recovery from this paper:

After two years, there was independent eating and speech competence of eight words (pronunciation slurred, mimicking prosody) with broad understanding. The patient moved from a prone to a free sitting position and crawled without cross-pattern, but using the arms. Independent passive standing, walking with support, and independent locomotion in a gait trainer was possible (video S5). He played imaginative games, and recognized colours, animals, and objects, assigning them correctly. Fine motor control improved to such an extent that he managed to steer a remote control car (video S6). At 30 months, he formed two-word-sentences using 80 words.

After 40 months, there was further improvement in both receptive and expressive speech competence (four-word-sentences, 200 words), walking (Crocodile Retrowalker), crawling with cross-pattern, and getting into vertical position.

And this is from a child who was a in a persistent vegetative state, who could neither speak, nor eat on his own, nor talk.

In animal studies, scientists have examined the therapeutic potential of cord blood. In a previous study with rats, RUB researchers revealed that cord blood cells migrate to the damaged area of the brain in large numbers within 24 hours of administration.  Umbilical cord stem cells are also known to secrete gobs of neurotropic molecules that stimulate neuron growth and differentiation, promote neuron survival, quell inflammation, staunch star formation in the brain (gliosis), and stimulate the growth and formation of blood vessels.

In March 2013, in a controlled study of one hundred children, Korean doctors reported for the first time that they had successfully treated cerebral palsy with someone else’s cord blood.

These results show that cord blood has tremendous therapeutic potential for pediatric neurological conditions.  This remarkable recovery is seemingly miraculous.  Certainly this merits more work and excitement.

Neural Stem Cells Slow the Progression of ALS

A research project that includes work done by 11 different institutions has tested the ability of neural stem cells to treat Lou Gehrig’s disease, which is also known as amyotrophic lateral sclerosis or ALS. ALS affects neurons in the central nervous system, particular in those cells in the spinal cord that allow voluntary movement (motor neurons). These neurons die off, and the patient loses the ability to move and, eventually, to breath. There is no presently no cure for this catastrophic and horrific disease.

Stem cell treatments have shown some success in laboratory animals, and this recent study examined the ability of neural stem cells, which have the ability to form neurons or those cells that support neurons, glial cells, to treat mice with a form of ALS that seems to closely resemble the disease presented by human ALS patients.

Neural Stem Cells
Neural Stem Cells

The combined work of these 11 different institutions showed that when these cells were transplanted into the spinal cords of laboratory mice afflicted with a form of ALS, symptoms of the disease decreased and the progression of the disease was greatly altered. When treated mice were compared with untreated mice, their movement ability and breathing were much better. Even more remarkable was the ability of these stem cells to slow the progression of ALS. Twenty-five percent of the treated mice survived for one year or more, which is three-four times longer than the untreated mice.

Even though neural stem cells can form neurons and other types of nervous system-specific cells, the neural stem cells in this experiments did not benefit mice by differentiating into new neurons. Instead, the transplanted stem cells prolonged the life of the troubled tissues by secreting molecules that are beneficial to the health of neurons and other cells in the nervous system. This menagerie of helpful molecules made by neural stem cells also stimulates other native cells in the nervous system to make their own fair share of protective molecules.

The transplanted neural stem cells also decreased the production of toxins by the diseased tissues and also diminished inflammation in the spinal cord.

In the words of the senior author of this study, Evan Y. Snyder, the director of Sanford-Burnham‘s Stem Cell and Regenerative Biology Program: “We discovered that cell replacement plays a surprisingly small role in these impressive clinical benefits. Rather the stem cells change the host environment for the better and protect the endangered verve cells. This realization is important because most diseases are now being recognized as multifaceted in their cause and their symptoms – they don’t involve just one cell type or one malfunctioning process. We are coming to recognize that the multifaceted actions of the stem cell may address a number of these disease processes.”

These studies demonstrate the potential neural stem cells hold for treating ALS and other nervous system disorders. However, Snyder tempered these results with this measured optimism: “While not a cure for human ALS, we believe that the careful transplantation of neural stem cells, particularly into areas that can best sustain life – respiratory control centers, for example – may be ready for clinical trials.”