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Gene Mutation To Help Develop Alzheimer’s Treatments

July 13, 2012

Connie K. Ho for redOrbit.com – Your Universe Online

5 million. That´s the number of people in the U.S. suffering from Alzheimer´s disease, according to a recent CNN article. Scientists recently announced that they had discovered a gene that fights Alzheimer´s. This is a positive step forward as the gene could help develop treatments to fight the disorder.

In the journal Nature, researchers explained how the gene that caused an early form of Alzheimer´s could also be created to produce an office effect, prohibiting the development of the disorder. According to the Guardian, carriers of the mutation have a 47% greater likelihood of living until 85 years of age as compared to those who don´t have the mutation. The findings also discuss how new drugs could copy the effect of the mutation.

Less than 1% of the population has these alleles,” explained Dr. William Thies, chief medical and scientific officer of research and advocacy group Alzheimer’s Association, in a Reuters Health article. “But many companies are working on compounds that target the mechanism they found and so might be encouraged by these results.”

Alzheimer´s is a common form of dementia and early signs include memory loss, mood swings, as well as feelings of isolation and withdrawal. The illness is progressive and those who are diagnosed with the disorder become dependent on others to help them with daily tasks. With Alzheimer´s disease, the brain is plagued with sticky plaques made of amyloid beta, a peptide. The amyloid beta is from the amyloid precursor protein (APP), which is a larger protein. Scientists have discovered about two dozen mutations in the APP genes that lead to early-onset Alzheimer´s within the last twenty years. Early-onset Alzheimer´s is normally diagnosed in people who are a bit younger than 65.

However, researchers from deCODE genetics in Iceland found that a new mutation in the APP gene does the opposite and has certain benefits. In the project, scientists sequenced the genomes of 1,795 Icelanders. It led to the discovery that participants of 85 years of age and older who had the beneficial mutation had a 81 percent less likelihood to develop Alzheimer´s when compared to others in the same group. In all age groups, those who had the variant genes were four times less likely to develop the neurogenerative disease.

“It confers extraordinarily strong protection,” noted lead scientist Dr. Kari Stefansson. “We found only five Alzheimer’s cases (out of thousands of people) with it.”

As well, the mutation is so rare that its discovery will help scientist in creating drugs that can prevent or treat Alzheimer´s. The mutation influences how APP is broken up and, after the brain produces the protein, the enzymes are broken into pieces. The enzymes are listed as alpha, beta, and gamma. The break up of APP by Alpha-secretase makes it so amyloid beta and plaques cannot be produced. As such, the fragment allows for growth and survival of the neurons.

On the other hand, the beta-secretase (BACE) works with the gamma-secretase to cut APP, so it can produce amyloid beta. The BACE then adheres to other amyloid beta fragments and forms plaques. Luckily, the beneficial mutation can stop the BACE’s ability to cut the APP and reduces the creation of amyloid beta by 40 to 50%t. Overall, it slows down the production of BACE, which hinders Alzheimer´s from developing.

A number of follow-up studies also showed that the DNA sequence with the mutation shielded the participants from decline in brain performance that is normally related old age. It proves that Alzheimer´s and other age-related neural problems are connected to a cycle of disorders and have the same basic cause.

“This gives you a proof of concept that if you inhibit BACE it will protect against Alzheimer’s,” remarked Stefansson in the Reuters Health article. “Big pharma has been working on inhibitors for beta-secretase for 15 to 20 years, and this offers greater confidence” that those efforts will pan out.”

According to Reuters Health, many companies are working on creating commands that can stop BACE actions.  For example, Merck presented early-stage human trails of MK-8931 last April. Vitae Pharmaceuticals and Boehringers Ingelheim are also working together to create a BACE inhibitor. Likewise, Eli Lilly and Co´s BACE inhibits is already in mid-stage human trials. However, it´ll mostly take at least four to five years or longer until the drugs become successful treatments.

“We know that the development of Alzheimer’s can be linked to a combination of genetic and lifestyle factors. We still have a lot to learn about what happens in the brain but this research offers new insight into a gene we already know is linked to the disease,” Anne Corbette of the Alzheimer´s Society told  HYPERLINK “http://www.guardian.co.uk/science/2012/jul/11/rare-genetic-mutation-alzheimers” the Guardian. “One in three people over 65 will develop dementia. This development offers interesting new information about how our genes might affect our chances of developing Alzheimer’s disease. It could also provide a new target for future investigations to find treatments to help people live well with dementia, or even find a cure.”


Source: Connie K. Ho for redOrbit.com - Your Universe Online