Jan 13, 2022

Gerold Schmitt-Ulms: from washing dishes to Alzheimer’s research

Research: Brain & Neuroscience, Our people
Gerold Schmitt-Ulms

Alzheimer’s disease is a fatal disease that eventually affects all aspects of a person’s life – how they think, feel and act. Over 500,000 Canadians are living with dementia today and Alzheimer’s is the most common type of dementia, accounting for 60 to 80% of all diagnoses, according to alzheimer.ca.

Dr. Gerold Schmitt-Ulms and his team are part of a large international effort trying to find ways to treat diseases like Alzheimer’s and improve the quality of life for those affected by them.

Now Professor in the Department of Laboratory Medicine and Pathobiology in the Temerty Faculty of Medicine, and part of the Tanz Centre for Research in Neurodegenerative Diseases, his interest in dementia started as soon as he left high school. 

Graduating from high school in Germany, he worked for two years - in lieu of the then mandatory German military service - in a long-term care home for individuals with severe disabilities, including brain damage. During that time, he “developed a lasting curiosity about how the brain works and an interest in finding solutions for dementias”.

One of the strongest dementia research teams in Germany at that time was a group, led by Dr. Eckhard Mandelkow, studying Alzheimer’s disease at a Max-Planck Unit in Hamburg. He relocated to Hamburg and joined this group as a student, initially cleaning dishes and filling pipet tip boxes. Eventually, he undertook PhD training there, studying the tau protein and the mechanisms that cause it to give rise to the notorious neurofibrillary tangles in Alzheimer’s. 

His next move was to San Francisco to work with Dr. Stanley Prusiner, a Nobel Laureate who discovered that the progression of a rare group of dementias relies on a specific protein, the prion protein (PrP), acquiring an alternative rogue shape. Once converted, the rogue protein induces other PrP molecules to also convert, thereby spreading the disease throughout the brain like an avalanche. 

It has become apparent that the same overall mechanism of disease spread is at play in prion diseases and in Alzheimer’s, and PrP may even play a critical role for the brain toxicity seen in Alzheimer’s disease.

Now, Dr. Schmitt-Ulms’ research group is focussed on finding a way to suppress the levels of PrP in the brain. “We know that having less PrP would likely cure prion diseases, ameliorate toxicity in Alzheimer’s and not have a negative health impact”, he says. “We recently discovered that PrP resides in the brain next to another protein that transports metals in and out of brain cells. The availability of drugs that inhibit these neighboring transport proteins made us wonder how brain cells may react to these inhibitors. As we hoped, immortalized human brain cells grown in petri dish cultures reacted by removing both the transporter and PrP from the cell surface and subsequently degrading them. We are now initially testing if this PrP removal approach can delay or prevent prion diseases.”

Prion diseases are much more easily replicated and studied in the lab in contrast to Alzheimer’s disease, thereby providing an excellent system for testing if this novel treatment approach has merit. If it works, the group will eventually try this approach in Alzheimer’s models.

The most important aspect of his research is whether it will make a tangible difference to peoples’ lives, says Dr. Schmitt-Ulms. “The main challenge doing this work is to know when an effort is not going to provide that benefit and therefore not a good use of limited time and resources.”

Alzheimer’s, and other dementias, may be devasting for those affected by them, but Dr. Schmitt-Ulms is hopeful that effective treatments will become available in the coming years. “Initially, these treatments are unlikely to represent cures”, he explains, “rather they may delay or ease suffering. With time, treatments will increasingly push back the age at which dementias manifest. Ultimately, we are striving for a future in which people can die in dignity of causes that inflict minimal end-of-life suffering and burdens on their families or society”. 

In the meantime, he advises ways to limit your risk of Alzheimer’s by looking after yourself, “We know that a lean and balanced diet, exercise, and an active social life reduce the overall dementia risk and can even slow symptom progression in people at risk of developing inherited forms of these diseases”. 

Dr. Gerold Schmitt-Ulms faculty profile

The Tanz Centre for Research in Neurodegenerative Diseases