International Stem Cell Corp. (ISCO) Metabolic Liver Disease Study Shows Solid Efficacy and Safety Results in Robust, Established Animal Model
International Stem Cell, the biotech developer of a powerful human parthenogenetic stem cell (hpSC) technology platform which yields pluripotent cells from unfertilized eggs that can be immune-matched to millions of humans irrespective of gender and racial genetic makeup, reported conclusions from their efficacy/safety study of hpSC-derived hepatocyte-like cells (HLCs) in congenital liver disorder associated with bilirubin metabolism, using a firmly established animal model.
The potential for this solution in Criggler-Najjar syndrome type 1 (CN1), a dangerous inherited metabolic disorder of the liver characterized by abnormal buildup of the toxin bilirubin due to the absence of the enzyme UGT1A1, is immense. CN1 often results in severe neurological problems and can even lead to irreversible brain and nervous system damage if it goes untreated. Luckily the company has previously reported on how HLCs engraft in Gunn rat livers, offering a solid animal model benchmark where the animal’s natural lack of the key enzyme grants exceptional clarity regarding therapeutic HLC dosing results.
As expected, the newest data from this pre-clinical study roundly confirms the bilirubin-level stabilization effects of implanting HLC in the rodents, as well as showing a serious initial punch after implantation that decreased bilirubin concentration in the blood serum considerably. Similarly, the safety metrics are essentially validated and one can look at the 16-week run without any safety signals going off, as well as the sustained offsetting of bilirubin levels up to the conclusion at the 19-week mark as sound indicators of the safety of this implanted HLC solution. In fact, overall liver morphology across the board in the treatment group showed no signs of cell rejection, inflammation, or tumor production, and the tissues were apparently completely undamaged.
VP of R&D for ISCO, Dr. Ruslan Semechkin, called this latest study a source of important evidence for the company’s HLC product in CN1 and conveyed everyone’s excitement at ISCO over now being primed to hammer out IND (investigational new drug) application requirements with the FDA in anticipation of Phase I clinical trials. The strength of the animal model really shines here and ISCO looks like they have another big emerging therapeutic winner on their hands, stemming once again from a powerful core biotech platform which the company has developed in therapeutic and regenerative hpSC applications. When taking a look at the company’s broader therapeutic programs based on this technology, it is easy to see the potential impact in diseases of the eye, nervous system, and liver. Cell therapy has proven clinically effective in all of those cases but until now the lack of safe, immune-matched human cells has been sorely lacking, making such therapy a mere pipedream.
This is a major breakthrough compared to extant Allogenic hepatocyte transplantation (HT), which has been used in CN1 and other metabolic liver diseases. The shortage of mature functioning cells and limited repopulation potential for grafted adult cells has hampered the effectiveness of HT sharply. There are several distinct advantages to the HLC approach besides hurdling this obvious cell shortage issue and the most striking one is the impressive long-term repopulation capacity of these HLCs, which stimulate a tenacious persistence in metabolic activity not seen in standard HT transplants. What’s more, because the HLC methodology allows for in vitro production and expansion, appropriate quantities can be derived and administered well before the onset of bilirubin-associated damage to the brain or nervous system ever occurs, with the HLC’s shoveling out enough enzyme to help the liver properly metabolize the toxin.
For more information on International Stem Cell Corp., visit www.InternationalStemCell.com