ALS Stem Cell Trials Move Forward

by Margaret Wahl on Tue, 2015-01-13 12:04


Article Highlights:
  • A phase 2a trial of BrainStorm’s NurOwn cells in 14 people with ALS in Israel showed the cells appeared safe and were associated with slowing of functional decline in nearly all trial participants; a phase 2 trial is ongoing in the U.S.
  • A phase 1 trial of Neuralstem’s NSI-566 cells in 15 people with ALS conducted in Atlanta showed the cells appeared safe and that six of the participants had slowing of disease progression; results of a phase 2 trial are expected soon.
  • MDA is not funding the BrainStorm or NeuralStem trials, but MDA-associated physicians are site investigators in both trials, and MDA laboratory research has contributed to development of the cells used in these studies.

Update (March 17, 2015): Neuralstem announced on March 12, 2015, that a phase 2 trial to test transplantation into the spinal cord of its NSI-566 neural stem cells showed the procedure was generally safe and well tolerated in 15 ALS patients (with one exception) and that stabilization or improvement in grip strength or overall motor function was seen in seven of the 15.

Update (Feb. 6, 2015): This article has been edited to reflect that patients in the BrainStorm trial in the U.S. will receive injections of NurOwn cells into a muscle and into the spinal fluid simultaneously, at a single point in time.

Update (Feb. 3, 2015): BrainStorm announced in a Feb. 3, 2015, press release, that its data safety and monitoring board found no cause for concern and recommended that the BrainStorm NurOwn trial in the U.S. continue as planned.


original story:

Stem cells -- cells at an early stage of development that can mature and fulfill specific roles depending on their environment and signals they receive – have intrigued scientists as a possible treatment for amyotrophic lateral sclerosis (ALS) for several years. Now, two biotechnology companies – BrainStorm Cell Therapeutics and Neuralstem – are reporting encouraging results from ALS clinical trials.

BrainStorm, located in New York and Petach Tikvah, Israel, has developed its NurOwn product using cells derived from patients' own bone marrow and then engineered in the laboratory to secrete chemicals that support the nervous system, known as "neurotrophic factors." Neuralstem, located in Germantown, Md., developed its NSI-566 cells from human spinal cord cells.

MDA is not supporting either trial directly. However, MDA-associated physicians are involved in both the BrainStorm and Neuralstem studies, and foundational research in stem cells by MDA has provided significant information for the field.

The principal investigator at the Boston site (Massachusetts General Hospital) in the BrainStorm trial is neurologist Merit Cudkowicz, who is the director of the MDA/ALS Center at that institution and has received significant MDA funding for research in ALS. In 2010, MDA funded Daniel Offen at Tel Aviv University in Israel to investigate how to engineer stem cells to produce neurotrophic factors.

Jonathan Glass, principal investigator for the phase 1 Neuralstem trial and a site principal investigator for the phase 2 trial, directs the MDA/ALS Center at Emory University in Atlanta and has received significant MDA funding for ALS research.

Nearly all 14 participants in BrainStorm's Jerusalem trial showed slowing of decline

Early in January 2015, BrainStorm announced positive final results from its phase 2a clinical trial of its patented stem cells, known as NurOwn. The trial was conducted in 14 people with ALS at Hadassah Medical Center in Jerusalem. All participants received the cells; there was no placebo group.

In a Jan. 5, 2015, press release, BrainStorm said that "nearly all subjects [in the study] experienced clinical benefit from treatment with NurOwn." Participants who showed a slowing of progression on tests of general motor function and respiratory function, as measured by the ALS Functional Rating Score (ALSFRS) and respiratory forced vital capacity (FVC), were judged to have shown benefit from the cells. The cells were assessed to be safe and well tolerated.

In October 2014, the U.S. Food and Drug Administration (FDA) gave fast track designation to BrainStorm's NurOwn cells for the treatment of ALS. Fast track designation is one of the mechanisms the FDA uses to speed up the review process for a drug that shows early evidence that it may provide benefit over available therapies.

"We are gratified to have the final data from this study and are very encouraged by the results," said Tony Fiorino, CEO of BrainStorm. "This study not only extends our earlier phase 1-2 findings regarding the safety of NurOwn, but also provides a consistent and highly promising picture of NurOwn's efficacy. In particular, I would highlight that we observed not only a highly meaningful reduction in ALS progression on mean [average] ALSFRS and FVC, but we saw subjects with prolonged stabilization and even improvements in function, and all this was achieved with just a single dose of NurOwn. We are excited to proceed to a multidose study to see if these positive results can be amplified and extended by administering repeated doses."

Phase 2 trial of NurOwn cells now open in U.S.

BrainStorm’s NurOwn cells, derived from patients’ bone marrow and made to secrete nerve-nourishing chemicals, are injected back into the same patients from whom they were derived, either into muscle ("intramuscular" administration) or into the fluid surrounding the spinal cord ("intrathecal" administration). Using patients' own cells is intended to minimize the risk of rejection of the injected cells by the immune system. The neurotrophic factors are intended to support and extend the survival of nerve cells that control muscle ("motor neurons"), the main cells that are lost in ALS, and of nervous system support cells ("glia").

A phase 2 trial of BrainStorm's NurOwn cells in ALS in the U.S. began in 2013 and is now open at sites in Boston, Worcester, Mass., and Rochester, Minn.

This trial will include approximately 48 adults with ALS, who will be randomly assigned to receive simultaneous intramuscular and intrathecal injections of NurOwn cells or of a placebo. The study will measure safety (adverse events) and change in ALSFRS and respiratory status.

Participants in the BrainStorm NurOwn trial must:

  • be 18 to 75 years old;
  • have an ALS diagnosis (possible, laboratory-supported probable, probable or definite, as defined by El Escorial criteria);
  • have experienced symptom onset more than one year but not more than two years prior to screening;
  • have limb weakness;
  • have an ALSFRS score of at least 30 at the screening visit;
  • have an upright slow vital capacity (SVC, a respiratory measure) of at least 65 percent of normal at the screening visit;
  • and meet other study criteria.

Participants in the Brainstorm NurOwn trial must not:

  • be using noninvasive or invasive (tracheostomy) ventilation;
  • be using a feeding tube;
  • have any unstable and significant medical condition other than ALS; or
  • have used any immunosuppressant medication within four weeks of the screening visit.

 (Note: This is not a complete list of study criteria.)

For details and contact information, see Phase 2 Study of Autologous MSC-NTF Cells in Patients With ALS, or enter NCT02017912 in the search box at

Neuralstem's NSI-566 cells appear safe and survive in spinal cord tissue in phase 1 trial 

In 2013, results from a phase 1 trial  of Neuralstem's NSI-566 neural stem cells showed the cells and the method used to transplant them directly into the spinal cords of ALS patients were safe and well tolerated. Of the 15 trial participants, six were showing a stable, very slowly progressing or improved disease course approximately two years after receiving the cells. Of the remaining nine, three had little change in the rate of progression of their ALS, and six had died. The trial was conducted at Emory University in Atlanta.

In November 2014, autopsy reports on the six patients who died during the phase 1 trial (of ALS or other causes) showed there was long-term survival – up to 2.5 years -- of the transplanted cells in their spinal cords, regardless of when drugs to suppress the immune system were stopped, suggesting that long-term immunosuppression may not be necessary for this type of transplantation therapy.

"The success of our therapy is predicated upon our cells' ability to survive long term and differentiate [mature] , providing neurotrophic [nerve-nourishing] support in the spinal cord and acting as 'nurse' cells for the patients' own motor neurons that are attacked by the disease," said Neuralstem's chairman and chief scientific officer Karl Johe in a Nov. 10, 2014, press release. "This new study presents an elegant demonstration that the NSI-566 cells survived long term and differentiated as expected," Johe continued, "[showing]  their promise as a neuroprotective, and neurorestorative, treatment for ALS and other neurodegenerative conditions."

Phase 2 study is complete, with results expected soon

A phase 2 study of NSI-566 stem cells in 15 people with ALS at three U.S. sites is ongoing but no longer recruiting new participants. This trial is designed as a "dose-escalation" study, in which higher doses are given to five sequential groups of participants depending on the safety seen at the preceding dose.

All 15 patients had received NSI-566 cells as of mid-2014. The first 12 received injections in the cervical (neck) region of the spinal cord in escalating doses, and the final three participants received injections in the cervical and lumbar (lower back) spinal cord. Final results are expected in early 2015.

"The completion of phase 2 of this important clinical research program is a major milestone, demonstrating that patients can tolerate the transplantation of high doses of cells and multiple spinal cord injections," said neurologist Jonathan Glass, the principal investigator for the site at Emory University in Atlanta in an Aug. 4, 2014, press release. "From both a clinical and scientific perspective, I think we are now ready to move forward toward a true therapeutic trial to test the efficacy of this surgical approach for slowing the course of ALS."



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