Research News

StemCells, Inc. Announces Results of Long-Term Follow-Up Study in Batten Disease

Human Clinical Data Encompasses Five Years of Post-Transplant Safety
NEWARK, Calif., Oct. 21, 2013 (GLOBE NEWSWIRE) – StemCells, Inc.(Nasdaq:STEM) announced today the results of a four-year observation study in patients with neuronal ceroid lipofuscinosis (NCL), also referred to as Batten disease, who had been transplanted with the Company’s proprietary HuCNS-SC® cells (purified human neural stem cells) in the initial Phase I study. Key results include long-term evidence of safety, up to five years post transplantation, for the surgical transplantation of the HuCNS-SC cells into multiple sites in the brain and at doses of up to one billion cells. The study results represent the first, and thus far only, multi-year data set following transplantation of neural stem cells into human subjects, and supports the feasibility of the Company’s approach in multiple neurological disorders. The data will be presented today by Nathan Selden, MD, PhD, FACS, FAAP, who was co-principal investigator in the studies, at the Congressof Neurological Surgeons Annual Meeting in San Francisco, California.”The NCL study enrolled patients suffering from a severe progressive neurological disorder and the study’s outcome shows that there were no long-term safety or tolerability issues associated with the cells, the immunosuppression regimen or the surgical procedure over the five years following transplantation,” said Dr. Selden, Campagna Chair of Pediatric Neurosurgery at Doernbecher Children’s Hospital and Oregon Health & Science University (OHSU), and incoming President of theCongress of Neurological Surgeons. “Our assessment of the patients’ cognitive and neurological function revealed stable scores in some tests, but the clinical outcomes were generally consistent with the expected course of impairment associated with this neurodegenerative disease. However, three of the six patients transplanted with HuCNS-SC cells have now survived more than five years post-transplant, and in a progressive neurodegenerative disorder, it is noteworthy that each have stable quality-of-life measures.”Stephen Huhn, MD, FACS, FAAP, Vice President, CNS Clinical Research atStemCells, Inc., added, “This was the first clinical test of our HuCNS-SC cells. We are very pleased to have accrued significant multi-year human safety and tolerability data for neural stem cell transplantation into the brain, unmatched in terms of both cell dose and duration of follow up thus far in the field. We are very grateful to all the investigators at OHSU and the families of the patients who were part of this ground-breaking study.”Six patients were enrolled in the Company’s Phase I clinical study in Batten disease. All six were transplanted with HuCNS-SC cells and followed for twelve months after transplantation. Five patients completed the Phase I study and subsequently enrolled in a four-year, long-term observational study, with three of the five surviving to the end of the four-year study. The long-term clinical data appear to be consistent with the natural history of the disease and conclusions about impacting the disease course cannot be made in an open-label trial. The reported adverse events are consistent with the underlying disease and there have been no safety concerns attributed to the HuCNS-SC cells. Magnetic resonance imaging scans of the brain show progressive atrophy consistent with the patient’s neuropsychological performance. Quality-of-life measures remained stable across all three surviving patients.

The Company previously reported post-mortem evidence of engraftment, migration and long-term survival of the HuCNS-SC cells following transplantation and the planned cessation of immunosuppression. The data were based on examination of the brains from three patients who expired from causes related to the underlying disease.

Combination treatment in mice shows promise for fatal neurological disorder in kids

By Caroline Arbanas (March 15, 2012)

Infants with Batten disease, a rare but fatal neurological disorder, appear healthy at birth. But within a few short years, the illness takes a heavy toll, leaving children blind, speechless and paralyzed. Most die by age 5.

There are no effective treatments for the disease, which can also strike older children. And several therapeutic approaches, evaluated in mouse models and in young children, have produced disappointing results.

But now, working in mice with the infantile form of Batten disease, scientists at Washington University School of Medicine in St. Louis and Kings College London have discovered dramatic improvements in life span and motor function by treating the animals with gene therapy and bone marrow transplants.

Click here for full article: https://news.wustl.edu/news/Pages/23561.aspx

Highlights from Biomarin’s Research & Development Day

(Note:  Below is an excerpt from BioMarin Pharmaceutical Inc.’s Press Release of December 8, 2012. To read the full press release, go to http://phx.corporate-ir.net/phoenix.zhtml?c=106657&p=irol-newsArticle&ID=1637904&highlight.) 

NOVATO, Calif., Dec. 8, 2011 /PRNewswire/ — BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today hosted a Research and Development Day where members of the company’s management team and industry experts provided an update on BioMarin’s product portfolio and advancements in the research and development pipeline.

“We believe 2011 has been a year of significant progress in both our late stage and early stage clinical development programs,” said Jean-Jacques Bienaime, Chief Executive Officer of BioMarin.  “This progress sets the stage for multiple data readouts in the coming year from key programs throughout our pipeline.  We believe these events will help move us forward in delivering more therapies that could make large impacts on the lives of patients suffering from several rare diseases.”

Program Highlights:

BMN-190 for Late infantile neuronal ceroid lipofuscinosis (LINCL) – Form of Batten Disease

At R&D Day, BioMarin also announced a new clinical program, BMN-190 for LINCL, one form of Batten disease.  An orphan neurodegenerative disease, LINCL is caused by buildup of lysosomal storage in the CNS. Tripeptidyl Peptidase-1 (TPP1) enzyme deficiency is due to a mutation in the gene CLN2.  Neurological symptoms present between ages two and four, with patients usually confined to wheelchair and blind by around age six.  Most patients are deceased between the ages eight and twelve. Incidence is estimated at 3.6 to 4.6 per million births and prevalence is between 350 and 1000 patients worldwide, likely higher due to under diagnosis.

The BMN-190 program is developing a TPP1 enzyme replacement therapy for treatment of LINCL patients.  Pharmacological effects, including functional improvement and life extension, have been robustly demonstrated in relevant animal models of LINCL.  Pharmacokinetic profile (CSF and plasma) and CNS distribution were favorable after ICV infusion.  Toxicity profile is clean after single and repeat ICV infusion administration.

“The BMN-190 program is a great fit in our growing pipeline.  LINCL patients represent a significant and unmet medical need in an orphan disease,” said Hank Fuchs, M.D., Executive Vice President and Chief Medical Officer of BioMarin.  “We believe we can leverage our expertise in biologic manufacturing and proven track record of expeditiously bringing life-altering therapeutics to patients to move this program forward rapidly. We look forward to updating you on advancements in this and other programs in our product pipeline.”

About BioMarin

BioMarin develops and commercializes innovative biopharmaceuticals for serious diseases and medical conditions. The company’s product portfolio comprises four approved products and multiple clinical and pre-clinical product candidates. Approved products include Naglazyme® (galsulfase) for mucopolysaccharidosis VI (MPS VI), a product wholly developed and commercialized by BioMarin; Aldurazyme® (laronidase) for mucopolysaccharidosis I (MPS I), a product which BioMarin developed through a 50/50 joint venture with Genzyme Corporation; Kuvan® (sapropterin dihydrochloride) Tablets, for phenylketonuria (PKU), developed in partnership with Merck Serono, a division of Merck KGaA of Darmstadt, Germany; and Firdapseâ„¢ (amifampridine), which has been approved by the European Commission for the treatment of Lambert Eaton Myasthenic Syndrome (LEMS). Product candidates include GALNS (N-acetylgalactosamine 6-sulfatase), which is currently in Phase III clinical development for the treatment of MPS IVA, amifampridine phosphate (3,4-diaminopyridine phosphate), which is currently in Phase III clinical development for the treatment of LEMS in the U.S., PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase), which is currently in Phase II clinical development for the treatment of PKU, BMN 701, a novel fusion protein of insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA), which is currently in Phase I/II clinical development for the treatment of Pompe disease, and BMN 673, a poly ADP-ribose polymerase (PARP) inhibitor, which is currently in Phase I/II clinical development for the treatment of genetically-defined cancers. For additional information, please visit www.BMRN.com. Information on BioMarin’s website is not incorporated by reference into this press release.

Forward-Looking Statement

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc., including, without limitation, statements about: the expectations of revenue and sales related to Naglazyme; the financial performance of the BioMarin as a whole; the continued clinical development and commercialization of Naglazyme; and actions by regulatory authorities. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: our success in the continued commercialization of Naglazyme; our ability to successfully manufacture our products and product candidates; the content and timing of decisions by the U.S. Food and Drug Administration, the European Commission and other regulatory authorities concerning each of the described products and product candidates; the market for Naglazyme; actual sales of Naglazyme; and those factors detailed in BioMarin’s filings with the Securities and Exchange Commission, including, without limitation, the factors contained under the caption “Risk Factors” in BioMarin’s 2010 Annual Report on Form 10-K, and the factors contained in BioMarin’s reports on Form 10-Q. Stockholders are urged not to place undue reliance on forward-looking statements, which speak only as of the date hereof. BioMarin is under no obligation, and expressly disclaims any obligation to update or alter any forward-looking statement, whether as a result of new information, future events or otherwise.

BioMarin®, Naglazyme®, Kuvan® and Firdapse™ are registered trademarks of BioMarin Pharmaceutical Inc.  Aldurazyme® is a registered trademark of BioMarin/Genzyme LLC.


Eugenia Shen
BioMarin Pharmaceutical Inc.
(415) 506-6570

Bob Purcell
BioMarin Pharmaceutical Inc.
(415) 506-3267

SOURCE BioMarin Pharmaceutical Inc.

Mutations in DNAJC5

Autosomal-dominant adult-onset neuronal ceroid lipofuscinosis (ANCL) is characterized by accumulation of autofluorescent storage material in neural tissues and neurodegeneration and has an age of onset in the third decade of life or later. The genetic and molecular basis of the disease has remained unknown for many years. We carried out linkage mapping, gene-expression analysis, exome sequencing, and candidate-gene sequencing in affected individuals from 20 families and/or individuals with simplex cases; we identified in five individuals one of two disease-causing mutations, c.346_348delCTC and c.344T>G, in DNAJC5 encoding cysteine-string protein alpha (CSPα). These mutations-causing a deletion, p.Leu116del, and an amino acid exchange, p.Leu115Arg, respectively-are located within the cysteine-string domain of the protein and affect both palmitoylation-dependent sorting and the amount of CSPα in neuronal cells.

Read full abstract (off-site link)