Aduhelm was recently approved by the FDA for the treatment of Alzheimer’s disease (AD). The FDA approval, the first in the history of the disease, was based on the drug’s potential to decrease Aβ plaque.

Yet, according to a report in ScitechDaily, there has been widespread disagreement on whether Aduhelm improves cognition.

Subsequently, the FDA modified the original approval recommending that it should be used specifically for mild cognitive impairment or early Alzheimer’s disease. At least forty percent of people treated with Aduhem reported severe side effects namely ARIA-e (cerebral edemas) and ARIA-H (hemorrhages).

Amyloid-Related Imaging Abnormalities (ARIA)

ARIA are termed as abnormal differences that are seen in MRI of the brain in Alzheimer’s patients.

Analyses of ENGAGE and EMERGE, two late-stage trials, found that one-quarter of the patients in those trials who took the new drug aducanumab (trade name: Aduhelm) were affected by ARIA. Results were published this week in JAMA Neurology.

Aduhelm is a monoclonal antibody (protein) designed to target amyloid beta and stimulate the immune system. The drug avoids the neurotoxic inflammatory effects that usually occur with standard treatments.

The approval process occurs at the same time Biogen and the FDA are attempting to determine whether Aduhelm was in any way responsible for the death of a Canadian woman. The woman was seventy-five years old and diagnosed with ARIA. She died during an extension trial.

Safety data reported:

• 425 of 1029 patients (41.3%) treated with a 10 mg dose of Aduhelm developed ARIA.
• 14% of these patients exhibited swelling or ARIA-E (edema) the most common adverse event seen in the pooled data.
• 35% or 362 patients were affected.
• 26% of the 362 patients had headaches, dizziness, confusion, and nausea.
• 1% had ARIA-(microhemorraging)
• 7% had ARIA-superficial siderosis (slow bleeding in the brain)
• 26% of the 362 ARIA-E patients experienced confusion, headache, nausea, and dizziness

All indications are that bleeding or swelling incidences were mild or moderate. However, scans revealed severe side effects in:

• 2 % of patients (swelling)
• 7% in patients with microbleeds, and
• 9% in patients with slow bleeding in the brain.

Biogen acknowledged that there were no deaths during the main portion of the trial. However, there is an ongoing investigation into the death of the seventy-five-year-old woman who passed away during the extension of the trial.

About the APOE4 Gene

According to analyses, the APOE4 gene was carried by a majority of patients who reported bleeding or swelling. Although these patients reported a decline in AD plaque burden, Aduhelm increased their imaging-related side effects.

You’ll have an MRI brain scan before you start treatment with Aduhelm. Aduhelm’s safety instructions recommend that the patient has an MRI brain scan within a year of beginning Aduhelm treatment and prior to each infusion number five through twelve. The scans will check for bleeding or swelling in your brain even though there may be no symptoms.

Dr. David Knopman at Mayo Clinic who did not participate in the analysis offered comments. He described the serious risks of ARIA as low but not trivial. About forty percent of patients who were treated with the antibody had serious side effects including hemorrhages and cerebral edemas.

Such side effects may worsen cognitive impairment in AD patients as the side effects cause synapses (the space between two neurons) and the death of neuronal cells.

Korean Institute of Science and Technology

Researchers at South Korea’s Science and Technology Institute created a new fusion protein drug that eliminates Aβ by way of a different mechanism.

On a positive note, the researchers created a mouse model of AD called A-Gas6 that removed Aβ not only more effectively but eliminated the inflammatory side effects linked to standard antibody therapy.

However, the researchers further stated that the antibody also creates inflammatory signals that eventually damage tissues in the brain.

The team used a process that removed dead cells and cleared the brain of Aβ. They noted that forty percent of participants treated with the monoclonal antibody developed serious side effects that included hemorrhages and cerebral edemas possibly resulting from inflammatory reactions in the brain.

Professors Chung and Kim explained efferocytosis as being paired with anti-inflammatory responses that maintain tissue balance (homeostasis). The researchers developed Gas6 which is an adaptor protein that impacts efferocytosis to redirect its target away from dead cells to Aβ plaques.

It is noteworthy that αAβ-Gas6 accomplished absorption of Aβ without signs of neurotoxicity or inflammation. This is in contrast to treatment with an Aβ monoclonal antibody.

In summarizing the merits of their approach, Professors Chung and Kim said that they believe it is a breakthrough in the treatment of AD. The professors point out that their process does not cause inflammatory side effects and is a novel therapy that will apply to other neurological disorders and immune diseases.

The professors have founded a therapeutics company designing Gas6 fusion proteins for Ab and for Tau for the treatment of AD symptoms.