in

Gene Targets for in Utero Therapy in Down Syndrome: Potentials and Pitfalls

Gene Targeting for in Utero Therapy in Down Syndrome: Potential Benefits and Challenges

The first thing that needs to be known is that there are no cures for Down syndrome. There are treatments that may improve the quality of life for some individuals with Down syndrome. However, these treatments have not been proven effective or safe. Therefore, they cannot be used to treat Down syndrome.

There are two main types of gene therapies that may be used to treat Down syndrome. These include: (1) gene transfer techniques and (2) targeted delivery methods.

In gene transfer techniques (e.g. viral vector), a virus that has been altered to remove its ability to cause an infection is used as a “vector” to deliver working copies of genes to a person’s cells. For example, genes may be transferred to a person’s liver cells to produce the missing or defective protein that is causing their disease.

In targeted delivery methods (e.g. liposomes), some of the patient’s cells are extracted and their outer layer of membranes (i.e. liposomes) are stripped off the cells.

A working copy of the gene is placed inside the cell and the liposomes are then used to carry the working copy of the gene into the patient’s cells.

Gene transfer techniques have been approved by the U.S. Food and Drug Administration to treat a severe type of blindness known as Leber congenital amaurosis. This condition may cause severe vision loss and legal blindness during infancy. It involves a mutation in a specific gene called RABGEF1.

The virus is altered so that it can transfer a working copy of the RABGEF1 gene to a person’s retina cells, where the non-working copy exists. The RABGEF1 gene is vital for healthy function and survival of the retina cell.

Some of the potential benefits of in utero gene therapy for Down syndrome may include:

Gene Targets for in Utero Therapy in Down Syndrome: Potentials and Pitfalls - - MedicalsNews

Repairing the extra copy of chromosome 21 (i.e. the cause of Down syndrome).

Reducing the risk of leukemia and other types of cancers.

Repairing congenital heart disease.

Reducing the severity of Alzheimer’s disease and dementia that often occurs in old age.

Reducing the risk of heart defects, intestinal blockages, and other congenital defects.

Targeted delivery methods have been used to transfer genes directly to the liver to treat children with a genetic disease called Adrenoleukodystrophy (ALD). People with this disease lack a working copy of the ABCD1 gene. The healthy copy of the gene is transferred into the liver cells. It directs the production of an enzyme that the body needs to break down certain fats in the body. Without the enzyme, these fats build up and damage the nerves throughout the body.

Gene Targets for in Utero Therapy in Down Syndrome: Potentials and Pitfalls - at Medical News

The healthy enzymes are not able to get past the blood-brain barrier to reach the brain. The ABCD1 gene is transferred into the liver cells using liposomes.

Some of the potential benefits of in utero gene therapy for Down syndrome may include:

Rebuilding the myelin sheath that insulates nerve cells and helps impulses travel faster through the brain.

Helping the nerve cells communicate more effectively.

Relieving some of the problems with visual acuity and hearing.

Helping the immune system fight off infection.

Targeting and destroying leukemia cells and preventing their return.

Enhancing the functioning of the digestive system and preventing future blockages.

Controlling the levels of cholesterol, triglycerides, and other fats in the blood.

Preventing and reversing memory loss and other cognitive impairments that often develop with old age.

Gene Targets for in Utero Therapy in Down Syndrome: Potentials and Pitfalls - | MedicalNews.com

Protecting nerve cells from damage due to low oxygen levels and low blood sugar.

There also is ongoing research into using in utero gene therapy to alter the genes of an unborn child in order to:

In addition to Down syndrome, there are hundreds of other genetic disorders that can be potentially treated in the womb.

Sources & references used in this article:

How a virus forms a protective shell to evade the immune system

Haloperidol Pharmacology