Int'l team identifies ALS gene

An international research team that includes doctors at Tel Aviv’s Sourasky Medical Center has discovered an additional defective gene that causes amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease or motor neuron disease).

The discovery will help provide families with genetic counselling and could lead to better understanding of why nerve cells break down and eventually, to treatments for the incurable and fatal neurological disease.

Only three out of every 10 cases of ALS are the result of family genetics; 70 percent of patients develop sporadic ALS, which is not connected to an inherited gene.

The discovery was published on Sunday night in the latest issue of the prestigious journal Nature. The head of the multi-center study was Prof. Robert Brown of the University of Massachusetts.

Nevertheless, said Prof. Vivian Drory of Sourasky’s neurology department and ALS clinic, and Tel Aviv University’s Sackler School of Medicine, insight into genetically inherited ALS will increase knowledge of the sporadic cases as well, as the mechanism is similar. Until recently, scientists though that 90% of ALS cases were sporadic, and only 10% genetically inherited.

Drory told The Jerusalem Post that the Israeli family members she investigated are of Sephardi origin, and that some of them have already died of the disease. As a result of the discovery of the gene, which is called profilin1, other Israeli families with ALS will also be examined.

Hospitals around the country diagnose some 120 to 140 new cases a year, and specialists are in the process of testing their genome to determine whether they have the sporadic or inherited disease.

Drory noted that the gene discovery was not a breakthrough, but added a piece to the ALS puzzle that could lead to better genetic counseling and eventually a treatment.

“It is another step forward,” she said. “We still have a long way to go.”

It is the first time Israelis have been involved in identifying a defective gene for ALS.

ALS is a disease of the nerve cells in the brain and spinal cord that control voluntary muscle movement. Gehrig, the famous American baseball star, apparently suffered from the sporadic type, as no members of his family were know to have it, said Drory.

In ALS, nerve cells – neurons – waste away or die and can no longer send messages to muscles. This eventually leads to muscle weakening, twitching and an inability to move the arms, legs and body. The condition worsens progressively. When the muscles in the chest area stop working, it becomes hard or impossible to breathe on one’s own, although the brain continues to function normally. ALS affects approximately two out of every 100,000 people worldwide.

Symptoms usually do not develop until after age 50, but they can start in younger people.

Persons with ALS experience gradual loss of muscle strength and coordination that eventually makes routine tasks – such as climbing stairs, getting out of a chair or swallowing – impossible. Muscles used in breathing or swallowing may be the first muscles affected. As the disease gains ground, more muscle groups develop problems.

Many patients die within 10 years, but less commonly, the progression of the disease halts, although at a debilitating stage. Such is the case of UK theoretical physicist Prof.

Stephen Hawking, who is already 70 years old and able to communicate only by looking at a special computer that synthesizes a voice and moves a cursor.

The defective genes that were discovered in the last decade, mostly in the US and all involved in familial ALS, include CDP43, FUS, VCP and ubiquilin. They involve the building of the skeleton of the neuron; when the cytoskeletons are not adequately constructed, ALS results. One defective gene is enough to cause the illness, said Drory.

As ALS victims are diagnosed when they are adults – even middle-aged – they are old enough to have children to whom they can pass on the familial type of disease.

Now that the profilin1 gene has been identified, genetic counseling can be provided to couples and pre-implantation genetic diagnosis (PGD) can be performed to determine which embryos have the defective gene, and thus prevent their implantation through in-vitro fertilization.

Couples who carry the gene, however, are not advised against getting married.

ALS occurs in all populations, and is not more prevalent among Jews.

Even if identical twins have the defective genes that cause ALS, they will not necessarily develop it at the same time.

One, said Drory, could get it at 40, and the other at 70.

“Genetic penetration by the gene is not uniform,” she said.