StemCells, Inc. has received approval from the US Food and Drug Administration (FDA) to initiate a clinical trial of the company's proprietary HuCNS-SC product candidate (purified human neural stem cells) to treat Pelizaeus-Merzbacher Disease (PMD), a fatal brain disorder that mainly affects young children. This phase I trial is designed to evaluate the safety and preliminary efficacy of HuCNS-SC cells as a treatment for PMD. Currently, there are no approved treatments for this disease.
This is the company's second FDA-approved clinical trial to evaluate HuCNS-SC cells as a potential treatment for neurodegenerative diseases. The first such study was the company's phase I clinical trial of HuCNS-SC cells to treat neuronal ceroid lipofuscinoses (NCL), or Batten disease. The phase I NCL trial will be completed in January 2009.
Patients with PMD are born with a gene mutation that results in insufficient myelination of nerve fibers in the brain, neurological impairment and eventually death. Myelin, which is produced by special cells called oligodendrocytes, insulates nerve fibers to allow electrical signals to be conducted normally. Other, more common, myelination diseases include cerebral palsy, transverse myelitis and multiple sclerosis.
Preclinical studies performed by the Company and its collaborators provide a rationale for potential therapeutic use of HuCNS-SC cells in myelination diseases. The company has demonstrated that, when transplanted into an animal model of hypomyelination (shiverer mouse), HuCNS-SC cells engraft and differentiate into mature oligodendrocytes and form myelin sheaths around host nerve fibers. The initial myelination data in the shiverer mouse was published in the Proceedings of the National Academy of Science (Cummings, et al. 2005) and the results of additional myelination studies were presented by Nobuko Uchida, Ph.D., the company's vice president of Stem Cell Biology, at the International Society of Stem Cell Research annual meeting in Philadelphia earlier this year.
"PMD is one of the most severe myelin disorders known to man. Children afflicted with this disease suffer progressive neurodegeneration and an untimely death. Unfortunately, they have no option for restorative treatment," said Stephen Huhn MD, FACS, FAAP, vice president and head of the CNS Program at StemCells, Inc. "We are very pleased to be the first company to initiate a neural stem cell trial for a myelination disease. Establishing safety and efficacy of our cells in patients with PMD may pave the way for similar studies in patients with other myelin diseases."
The company has begun the process of seeking approval by the Investigational Review Board (IRB) of potential clinical trial sites in order to begin enrolling patients.
PMD is a rare, degenerative, central nervous system disorder and is one of a group of genetic disorders known as leukodystrophies. Leukodystrophies involve abnormal growth of the myelin sheath which is the fatty substance-or insulator-on nerve fibers in the brain and spinal cord. PMD is most commonly caused by a genetic mutation that affects an important protein found in myelin, proteolipid protein (PLP). PMD is most frequently diagnosed in early childhood and is associated with abnormal eye movements (nystagmus), abnormal muscle function, and in some cases seizures. The disease form in early infancy is referred to as connatal PMD and diagnosis in later childhood is most typically associated with the classic form. The neurological course of both forms is marked by progressive deterioration resulting in premature death.
StemCells' lead product candidate, HuCNS-SC cells, is a purified composition of normal human neural stem cells that are expanded and stored as banks of cells. The company's preclinical research has shown that HuCNS-SC cells can be directly transplanted; they engraft, migrate, differentiate into neurons and glial cells; and they survive for as long as one year with no sign of tumour formation or adverse effects. These findings show that HuCNS-SC cells, when transplanted, act like normal stem cells, suggesting the possibility of a continual replenishment of normal human neural cells.
StemCells, Inc. is a clinical-stage biotechnology company focused on the discovery, development and commercialization of cell-based therapeutics to treat diseases of the central nervous system and liver.