Team of scientists develops peptides to stem Alzheimer’s

Mariecar Jara-Puyod, Senior Reporter

After three years of collaboration, a team of academician-scientists from the UAE, US and Sweden has designed and developed peptides believe to inhibit the progress of another group of proteins and protect the brain from the neurodegenerative Alzheimer’s Disease.

In order to push forward their discovery, New York University (Abu Dhabi) Biology Associate Professor Mazin Magzoub, New York University (New York) President & Chemistry Professor Andrew Hamilton, and Stockholm University Biophysics Professor Astrid Grusland will now proceed to the testing of their engineered “cell-penetrating peptides” (CPPs) on animals.

“We will now test these CPPs in animal models of Alzheimer’s Disease, such as the Caenorhabditis elegans (roundworms) and mice. A successful outcome in these organisms will go a long way towards confirming the therapeutic potential of these proteins,” biophysicist Magzoub told Gulf Today on Wednesday.

Magzhoub was interviewed on the scientific breakthrough as Sept. 21 is “World Alzheimer’s Day,” observed every year to continually spread and raise awareness on this commonest form of dementia, said to be inheritable from parents with head injuries, hypertension and depression as the risk factors.

The full research of the Magzoub-Hamilton-Graslund team titled “Designed Cell-Penetrating Peptide Inhibitors of Amyloid Beta (AB) Aggregation and Cytotoxicity” had been published in the “Cell Reports Physical Science” last February.

ABs are the proteins or amino acids described as plaque and found in Alzheimer’s Disease sufferers.

Enquired on the relevance of the newly-designed CPPs when a Cambridge University study had reflected that Alzheimer’s Disease is preventable in one of three cases through lifestyle modifications such as stubbing the cigarette and regular physical exercises, Magzoub replied: “It is true that the Cambridge University study has shown that one in three cases worldwide (can be addressed through lifestyle changes). However, it also means that the majority of the cases are not due to modifiable risk factors. This strongly underscores the need for effective therapeutics that currently do not exist.”

The three have known one another for several years prior to their Alzheimer’s Disease laboratory work. Magzoub was “exposed to CPPs” when he was at the Stockholm University laboratory of Graslund for his doctorate degree. He was a member of the research team of Hamilton at the Yale University and collaborated on the development of “small molecule inhibitors of Type II Diabetes-associated islet amyloid polypeptide.”

They pursued the Alzheimer’s Disease laboratory work having observed the “misfolding of certain proteins” which damage the brain neurons in other neurodegenerative diseases namely Huntington’s and Parkinson’s.

“Our laboratories began collaborating three years ago to engineer CPPs as a new class of (AB) inhibitors with the potential to overcome the shortcomings of many current AB inhibitors, including poor tissue penetration like the inability to cross the blood-brain barrier and inefficient cellular uptake,” related Magzoub.

He said: “CPPs are peptides (small proteins) that have the ability to efficiently enter cells which is something that many potential therapeutics are unable to do.”

Saying that these designed CPPs are able to attach to the ABs found in Alzheimer’s Disease patients, Magzoub added these can also cross the blood-brain barrier, a major hindrance to access of therapeutics to the brain.”

Hence, these CPPs impede the accumulation or aggregation of the ABs in the brain resulting in Alzheimer’s Disease.

Magzoub said the Alzheimer’s Disease project was a humongous undertaking. It needed the assistance of other experts particularly in the fields of Chemical Biology and Cell Biology. He was thankful to his colleague at New York University (Abu Dhabi), Chemistry Professor Gennaro Esposito.

A recent report said there is a new form of Alzheimer’s Disease (AD) identified as “Progressive Dysexecutive Syndrome (dAD), the onset of which is by age 40.