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.”
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.”
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 Firdapse™ (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.
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.
BioMarin Pharmaceutical Inc.
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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.