What can you do to #ChallengeALS




Leadership from Brainstorm Cell Therapeutics announced results from their recently completed U.S. phase II stem cell study of NurOwnŽ in patients with ALS through a press release and webinar. Below we provide some detail on this study.

The Brainstorm stem cell trial is based off of NurOwn, which is a cell therapy platform centered on mesenchymal stem cells derived from bone marrow samples given by the participants in the trial. They are induced to secrete neurotrophic factors (MSC-NTF), which are a type of nutrient for cells that was previously show to have protective effects in animal models of neurodegenerative disease.
Study Goals:
The main goal of the study is to evaluate safety and tolerability. Despite the small size of the study, researchers conducted pre-efficacy measurements to preliminarily understand whether NurOwn has a beneficial effect in people living with ALS or not.

The Study:
This is a complementary study to the phase I/II and IIa clinical trial recently completed in Israel and was published in JAMA Neurology in January 2016. It was conducted at three sites in the U.S. including Massachusetts General Hospital under the leadership of Dr. Merit Cudkowicz, University of Massachusetts Medical School under the leadership of Dr. Robert Brown, and the Mayo Clinic under the leadership of Dr. Anthony Windebank.
This phase II study was a randomized, double-blind, placebo-controlled, multi-center study conducted in 48 people living with ALS. Thirty-six patients received NurOwn cells administered via combined intramuscular (into the muscle) and intrathecal (into the spinal cord) injection. Twelve received placebo. Participants were followed monthly for approximately three months before treatment and six months following treatment and were assessed at 2, 4, 8, 12, 16 and 24 weeks.
Safety and tolerability assessments, along with pre-efficacy studies were also included, such as changes in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score, Slow Vital Capacity (SVC) and muscle strength.
Results and Conclusions:
The study achieved its primary objective, demonstrating that NurOwn was safe and well-tolerated. NurOwn also achieved promising preliminary efficacy results, which could potentially translate into a clinically meaningful benefit in the future. However, the study’s design and small participant size does not allow for a full picture of the efficacy in slowing or stopping ALS progression. Next, the company is looking towards a larger, multi-dose, double blind NurOwn trial in Israel and the U.S.
“The data is very encouraging for a well designed phase II study showing safety as well as some preliminary efficacy data providing strong support for a larger study,” stated Dr. Lucie Bruijn, Chief Scientist at The ALS Association.
For more information about the trial, please visit here for a link to today’s webinar given by Brainstorm and the lead researchers involved in the trial, along with slides from the webinar. Click here for the press release.



Choosing stem cells with specific desirable properties can improve their therapeutic potential, according to a new research study supported by The ALS Association. The study, led by Stefania Corti, M.D., Ph.D., Assistant Professor of Neurology at the University of Milan, and her colleagues, was published in the journal Human Molecular Genetics on June 6, 2016.
Stem cells are cells that are capable of developing into multiple different types of cells, including neurons and cells that nourish and protect them. Subpopulations of stem cells differ from one another in several ways, including their ability to migrate and to promote production of growth factors that aid neurons. To test the potential of one such subpopulation, Dr. Corti isolated stem cells with both migratory and growth factor-production abilities. She mixed them with motor neurons that were cultured with ALS-causing astrocytes, and found that the motor neurons survived longer and grew better as a result. When the stem cells were injected into a SOD1 mouse model of ALS, they migrated and supported neurons in the spinal cord, reducing signs of inflammation and promoting growth, and demonstrated some survival benefit in the mice.
“This important work increases our understanding of the potential of stem cells for therapy in ALS,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association. “As we continue to develop this therapy, it may be very useful to focus on those cells with the migration and growth-promoting properties demonstrated here, but understand that there are still many hurdles to overcome to take this to clinical trials. So far, efficacy in the clinic is unclear.”




Mitsubishi Tanabe Pharma Corporation (MTPC), which is locally based in Jersey City, N.J. with a head office in Osaka, Japan, announced yesterday that a New Drug Application has been submitted to the U.S. Food and Drug Administration (FDA) for edaravone (MCI-186) for the treatment of amyotrophic lateral sclerosis (ALS). Those in the ALS community may have questions about what this means for them. Below we provide some background information on edaravone.
What is edaravone?
Edaravone is believed to act as a free radical scavenger, a compound that works by getting rid of toxic waste generated as a normal by-product of cell function. In ALS it is thought that these by-products are not as effectively removed and the compound may be neuroprotective by relieving the effects of this oxidative stress. The increase in oxidative stress is thought to damage motor neurons (cells that die in ALS).
History of edaravone
Originally, edaravone was approved in Japan to treat stroke. A phase III double-blind placebo-controlled study (MCI186-J16) was conducted in people living with ALS to confirm safety and efficacy of edaravone. This study showed that edaravone did not significantly differ from placebo using the ALS Functional Rating Scale Revised (ALS-FRS-R). Investigators next conducted another phase III trial with a sub-group of people living with ALS that had greater baseline functionality. Results demonstrated that people living with ALS that had a forced vital capacity of >80% and had disease less than 2 years showed the greatest benefit with a statistically significant improvement in the (ALS-FRS-R). It was also established in an exploratory study that edaravone has no benefit from treatment in more advanced ALS cases.
In 2015, edaravone was approved for use as a treatment for ALS in Japan and South Korea using intravenous injections of the drug. In the same year, the FDA and European Commission granted Orphan Drug Designation for edaravone. The Orphan Drug Act gives special status to a drug that treats a rare disease like ALS and gives incentives for pharmaceutical companies to develop said drug. Mitsubishi Tanabe Pharma is continuing to monitor edaravone’s effects in a post-market survey now that it has been approved. This should shed light on whether or not the drug improves survival.

Treeway BV in the Netherlands under the leadership of co-founders Bernard Muller and Robbert Jan Stuit is about to start a phase II/III clinical trial to test an oral version of edaravone (TW001). Taking the drug orally would be less invasive and more convenient to treat chronic ALS compared to the intravenous infusions of the drug. The TW001 efficacy study is a European study, so only people living in proximity to participating sites can participate.
A New Drug Application for edaravone was submitted in the U.S.
A new drug application (NDA) is a means for pharmaceutical companies to formally propose that the FDA approves a new drug for sale and marketing in the U.S. The NDA gives a full picture of the new drug, such as data from the clinic trials and animal studies, how the drug behaves in the body and how it is manufactured, processed and packaged. Mitsubishi Tanabe Pharma submitted edaravone to the FDA to request its approval in the U.S.
What’s next?
Edaravone is currently not approved by the FDA for use in the United States. It is not known yet whether the FDA will automatically approve edaravone in the U.S. or whether the FDA will require a phase III study in the U.S.




The ALS Association and Target ALS Partner to Uncover the Connection Between Ancient Retroviruses and ALS and expand Biorepository Efforts

In partnership with Target ALS, The ALS Association is using part of its original investment in the Center for Genomics of Neurodegenerative Disease (CGND) at the New York Genome Center (NYGC) to create a valuable resource of RNA sequence data generated from tissue samples and induced pluripotent stem cells (iPSCs).
Target ALS, who is partnering with ALSA, is a privately funded consortium of researchers from academic and biotech/pharma laboratories entirely focused on finding a treatment for patients living with ALS.
Target ALS has also established a multicenter ALS post-mortem tissue core, directed by Dr. Ostrow, and The ALS Association has partnered to expand this resource to collect fluid samples from people living with ALS. The current partnership to fund a study at NYGC’s CGND to sequence HERVs read from samples taken from people living with ALS compared to healthy people (i.e. controls) will exploit these resources.

Their newest announcement is that since they are focused on finding new treatments for amyotrophic lateral sclerosis (ALS), they have selected  RUCDR Infinite Biologics as the biorepository for banking and distributing the foundation’s human stem cell lines to be used in industry and research. “This is the first initiative of its kind to assist ALS researchers in academia and industry by providing stem cells lines for their use while permitting them to retain the data and intellectual property generated by their work,” Dr. Manish Raisinghani, president of the Target ALS Foundation, said in a press release.
More than 50 academic researchers and two dozen companies are using the foundation’s stem cells a number that should increase exponentially in time. Currently, Target ALS has 10 stem lines in its repository. Through collaboration with RUCDR, the number is expected to grow and include genetically modified stem cell lines. The National Institute of Neurological Disorders and Stroke (NINDS) Human Cell and Data Repository (NHCDR), led by RUCDR and operated under a grant, has added the Target ALS stem cell bank to its online catalog.