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Home » Neurology » Quest to combat rare form of dementia

Dr Arnon Rosenthal

CEO and Co-founder, Alector

Dr Robert Paul

Chief Medical Officer, Alector

Scientists are embracing a therapeutic concept used in oncology to find a treatment for a rare form of dementia.

Frontotemporal dementia (FTD) is a rare disease unlike Alzheimer’s disease but runs in families and has a similar deep impact on patients and their families.

With no recognised disease-modifying treatment, FTD has become a focus for an immuno-neurology approach with scientists. By targeting the brain’s immune system, scientists are attempting to alter the course of disease which leads to the condition, in the same way immunotherapy is applied in cancer patients.

Dr Arnon Rosenthal, CEO and co-founder of Alector – which is working on a therapy for FTD – explains that there is an unmet need in FTD as no disease modifying therapies are available, the only options for patients are symptomatic treatments.

Genetic composition

Alector is adopting a different approach and aims to “recruit the immune system” to treat the disease, similar to immuno-oncology. Dr Rosenthal says: “Instead of trying to kill cancer cells with chemotherapy and radiotherapy, clinicians are now effectively recruiting the immune system for cancer therapy. We are using a similar approach. Instead of trying to remove individual pathologies such as the beta-amyloid peptide, we recruit the brain immune system to combat neurodegenerative diseases.”

In the last decade, ~100,000 Alzheimer’s and FTD patients have had their genetic composition determined to assess those who have genes placing them at highest risk. This has triggered research to focus on developing drugs which functionally modulate genes which control the immune system in the brain, and utilise the brain immune system to fight dementia.

The impact of the disease

FTD is often misdiagnosed, which Dr Rosenthal says increases the need to raise awareness of it among families, GPs and neurologists globally. “FTD is a very lethal disease,” he says.

People die within 7-10 years of diagnosis because the brain is eventually destroyed, but we want to both slow the progression of the disease and begin treatment before individuals show symptoms of the disease.

Dr Robert Paul, Alector’s Chief Medical Officer, says that Alzheimer’s disease affects millions of people, with age one of the highest risk factors. However, FTD is different, it affects some 150,000 people in Europe and America, though the actual figure could be higher.

“With FTD, other parts of the brain are affected and that affects what the symptoms are,” he says. “The neurons that are dying are in the frontal and temporal lobe, so people start behaving differently, become depressed or aggressive and have language problems. Because FTD is so unusual, it takes a long time to diagnose these patients who are younger than Alzheimer’s patients and in their 40, 50s and 60s. Now we know that there are familial cases of FTD, ~ 40% of cases can be explained by a genetic mutation.”

New clinical trials

Progranulin is important in regulating the immune response in the brain and deficiency in the progranulin protein causes FTD. Alector is conducting a Phase III trial, to determine if the drug can alter the course of FTD in individuals with a progranulin mutation by aiming to restore progranulin levels to that of healthy individuals.

The clinical study includes both those with FTD as well as at-risk participants who have the genetic mutations and the protein deficiency but are still healthy.

Dr Paul explains that mutations in this progranulin gene lead to a progranulin deficiency that causes the disease. “We think by restoring progranulin levels, we can inhibit the disease progression.”

Our vision, and mission, is to make degenerative brain disorders like FTD diseases of the past.

Broad approach

Results of the Phase III trial, which started in July 2020, are expected within the next few years. There is also hope that the immuno-neurology approach may work for other neurological diseases such as Alzheimer’s, Parkinson’s or Huntington’s disease.

Alector is advancing clinical trials with immuno-neurology drugs also for Alzheimer’s disease, ALS (Amyotrophic Lateral Sclerosis) and Parkinson’s disease. “We are looking at this as a broad new approach for the main neurodegenerative diseases,” says Dr Rosenthal. “Our vision, and mission, is to make degenerative brain disorders like FTD diseases of the past.”

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