The stock prices of Korean pharmaceutical companies developing Alzheimer's disease treatment dropped as suspicions arose about the possible manipulation of a research paper on amyloid beta, a key substance in dementia treatment.

Cellivery Therapeutics, a company developing iCP-Parkin, a Parkinson's disease treatment that removes beta-amyloid aggregates, closed at 15,450 won ($11.75) on Tuesday, down 3.74 percent from the previous trading day. The company's shares also fell 8.02 percent on Monday.

Shares of other pharmaceutical companies developing Alzheimer's treatment have also fallen for the past two days. GemVax & Kael has fallen 0.73 percent, ABL Bio, 6.5 percent, and People Bio, 9 percent.

The drop in share prices follows a report from the international academic journal "Science" on July 21 that accused the thesis in Nature in 2006 by Professor Sylvain Lesné at the University of Minnesota of manipulating data images.

Nature issued a publisher's note on July 14, saying that it was investigating the concerns about the 2006 paper and that "a further editorial response will follow as soon as possible."

The paper published the discovery of amyloid beta 56, a protein that causes Alzheimer's, in animal experiments using mice. The hypothesis was a key study in the development of Alzheimer's disease treatment for decades and has been cited nearly 2,300 times.

Experts believe that if the hypothesis turns out to be false, it could significantly impact the pharmaceutical industry as Korean and multinational pharmaceutical companies, such as Biogen, Eli Lilly, and Roche, have researched dementia treatments based on the hypothesis.

For instance, Biogen's controversial drug Aduhelm was approved last year as the first treatment to address the underlying biology of Alzheimer's disease by the U.S. Food and Drug Administration to break down amyloid beta.

However, some experts said that even if the academic society deems the manipulation true, it will have a limited impact. It does not mean that the entire related research will be denied.

"There have been many independent studies conducted on the amyloid beta hypothesis and other substances that affect the brain besides amyloid beta 56," said Lee Jun-soo, an analyst for Prophet Asset Management, to Korea Biomedical Review. "Rejecting the hypothesis as a whole may be an overinterpretation."

However, with the academic community's credibility of the amyloid beta hypothesis coming into question, Korean pharmaceutical companies are trying to distance themselves from the paper as much as possible.

"The key to developing a treatment for Alzheimer's is to remove the deposition of bad proteins that kill nerve cells," Cellivery Therapeutics CEO Jo Dae-woong said to Press 9, a medical newspaper. "Therefore, it is important to focus on the effect rather than the cause."

Jo stressed that dozens of hypotheses are considered the main cause of Alzheimer's disease, ranging from genetic causes to heavy metal deposition.

"The issue of whether the deposition of beta-amyloid protein is the cause of Alzheimer's disease has existed for a long time, but the important thing is that the cause does not significantly affect the development of therapeutic agents," Jo said. "Until now, the only lesions found to have a clear relationship with Alzheimer's in numerous studies were beta-amyloid and tau protein."

Although the exact cause of the pathogenesis is unknown, it is clear that the deposition of these proteins is associated with neuronal death.

Jo stressed that his company's candidate, iCP-Parkin, is a protein that labels brain cells to remove useless and wrong proteins such as beta-amyloid and tau protein.

"Therefore, the paper will not affect our drug even if the manipulation allegations are true," he said.

GemVax & Kael offered a similar opinion regarding the matter.

"The paper in question provides a basic rationale for the so-called 'amyloid hypothesis' that states Alzheimer's disease is caused by the deposition of amyloid beta in brain neurons," a GemVax & Kael official said. "However, Alzheimer's disease cannot be explained by a single cause."

There are several hypotheses related to the pathogenesis of Alzheimer's disease, the representative ones being the amyloid hypothesis, the tau knot hypothesis, the immune cell-related neuroinflammatory hypothesis, and the vascular hypothesis, she added.

The official stressed that the company's drug GV1001 is a drug that acts on various mechanisms other than those related to amyloid beta. Even if the manipulation of research on amyloid beta turns out to be true, it will not affect the company's drug development process.

"We will do our best for the ongoing phase 3 clinical trials in Korea and phase 2 clinical trials in the U.S.," she said.