Rare Disease Research Program
Thirty million Americans suffer from rare disease and 80 percent of these rare diseases are due to genetic mutations. Thirty percent of patients with rare disease will die by age 5. Currently genetic diseases are treated by the pharmaceutical industry with small molecules, enzyme replacement therapy (ERT) or gene therapy. There are shortcomings with each of these approaches.
Small molecules target a specific protein target responsible for a genetic disease. Typically, pharmaceutical companies frequently focus on small molecules for two basic reasons. First, the drug company expertise historically lies in organic chemistry. Second, drug companies are looking for a key chemical reaction at the protein level that regulates a disease state. However, diseases have redundant abnormal chemical pathways that cannot be suppressed by a small molecule regardless whether a disease is rare or common.
Many rare genetic diseases are due to a mutation in a required enzyme necessary for maintaining cell metabolism, growth and health. Treatment for these enzyme disorders is managed by administering a synthetic normal enzyme replacement-a process called ERT. Yet, ERT have several shortcomings. First, delivering ERT to the central nervous system (CNS) for genetic disorders that have significant neurological manifestations is challenging because proteins are too big to cross the blood brain barrier (BBB). Second, protein biologics are most commonly produced from Chinese Hamster Ovary (CHO) cells which does not produce a perfect copy of the native human protein. The resulting CHO-based protein has suboptimal biological activity and safety.
While gene therapy may potentially correct an enzyme defect in monogenic disorders, gene therapy poses several challenges. First, repeated gene delivery using conventional viruses invokes an immune response, which leads to drug resistance and systemic or regional inflammatory effects. Second, the most common virus, AAV, is limited by the size of a gene that can be packaged into this virus. Third, gene therapy does not correct the collateral inflammatory effects caused by genetic diseases. Lastly, the cost of gene therapy is typically very expensive and the first FDA-approved product cost nearly 1 million dollars. With tens of millions of Americans suffering from genetic diseases, the estimated cost to treat all patients with gene therapy would double the national healthcare budget.
From an ethical perspective, some proteins are produced from a cell line called, HEK293, which was produced from abortions in the 1970s. Also, all gene therapies use HEK293.
The Institute's rare disease research centers on developing adult stem cell that will replace the HEK293. The Institute co-developed CET-JP2-2007 with Cellular Engineering Technologies. CET-JP2-2007 is a versatile adult stem cell with the following features:
A universal stem cell therapy that offers several advantages over gene therapy. First, stem cells can offer cell protection and cell repair through broad mechanisms and abrogate inflammation and cell death regardless of the cause. Second, CET-JP2-2007 can synthesize and secrete fully human biologics without limitation to the size of the gene unlike AAV. Third, stem cells naturally travel to sites of inflammation and injury. Fourth, cell therapy would be much less expensive because the manufacturing process is modular and the cost would be absorbed within the market for treating common diseases.
CET-JP2-2007 is a versatile cell that can produce fully human proteins. This stem cell has faster growth than HEK293, which can increase the protein production in less time and cost. The Institute is conducting research that improves the ability of ERT to cross the BBB and penetrate the CNS and exhibit longer duration of action than current ERT.
CET-JP2-2007 has the potential to produce standard viruses for gene therapy.