In a pilot study of two patients monitored for two years, an international team of researchers slowed the onset of the debilitating brain disease X-linked adrenoleukodystrophy (ALD) using a lentiviral vector to introduce a therapeutic gene into patient’s blood cells. Although studies with larger cohorts of patients are needed, these results suggest that gene therapy with lentiviral vectors, which are derived from disabled versions of human immunodeficiency virus (HIV), could potentially become instrumental in treating a broad range of human disorders
Other Gene Therapy Success and Progress
Lungs too damaged for use in transplant operations may be salvageable through a gene-based technique, doubling or tripling the supply of organs.
The flawed lungs could be removed from donors’ bodies after death and repaired using the gene IL-10, which lowers inflammation. 1800 people in the US are awaiting lung transplants.
Gene Therapy helps treat a form of blindness The condition is known as Leber’s congenital amaurosis and there are 2000 people in the US who have it.
A number of companies are developing gene therapies and 320 trials are under way or cleared to begin by U.S. regulators, said Karen Riley, a U.S. Food and Drug Administration spokeswoman. Genzyme Corp. of Cambridge, Massachusetts, will begin a human trial using gene therapy next year to treat macular degeneration, the leading form of age-related vision loss, said John Lacey, a Genzyme spokesman
Researchers at the California Institute of Technology (Caltech) have shown that a highly specific intrabody (an antibody fragment that works against a target inside a cell) is capable of stalling the development of Huntington’s disease in a variety of mouse models.
In the new trial, reported today in the journal Science Translational Medicine, Bechir Jarraya and colleagues at the Molecular Imaging Research Center in Fontenay-aux-Roses, France, mimicked Parkinson’s in monkeys by giving them a neurotoxin that causes movement problems characteristic of the disorder. The researchers then injected three genes involved in dopamine production into the brains of the monkeys, as well as specially designed probes to measure dopamine levels in the brain, monitoring the animals for up to three and a half years. The gene therapy restored concentrations of dopamine in the brain, corrected movement problems, and prevented dyskinesias–without any severe adverse side effects. An early stage human clinical trial using the same dopamine gene therapy approach is now underway.
The Modified HIV Gene Therapy
The healthy ALD protein was expressed in about 15 percent of blood cells, yet surprisingly this low level was sufficient to slow brain disease in ALD. “This percentage of correction will not be sufficient for all diseases,” warns Aubourg. “There is a lot of work to be done to make this gene therapy vector more powerful, less complicated, and less expensive. This is only the beginning,” he said.
Gene therapy is not without serious risks. Like other retrovirus vectors, the HIV-derived lentivirus vector is tasked with inserting the therapeutic gene in the chromosomes of the patients’ cells. In a worst case scenario, this action could disturb the biology of the cells and patients could end up with leukemia; this outcome has occurred in past gene therapy trials. “The HIV-derived lentivirus vector basically has this same risk, although the design of the vector makes patients less prone to this side effect,” said Aubourg.
Prevalance Rate: approx 1 in 20,000 or 0.00% or 13,600 people in USA
Adrenoleukodystrophy (ALD) (also known as “Addison-Schilder Disease,” “Siemerling-Creutzfeldt Disease,” and “Schilder’s disease”) is a rare, inherited disorder that leads to progressive brain damage, failure of the adrenal glands and eventually death. ALD is one disease in a group of inherited disorders called leukodystrophies. Adrenoleukodystrophy progressively damages the myelin, a complex fatty neural tissue that insulates many nerves of the central and peripheral nervous systems, eventually destroying it. Without myelin, nerves are unable to conduct an impulse, leading to increasing disability as myelin destruction increases and intensifies.